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  • 1.
    Axfors, Cathrine
    et al.
    Uppsala Univ, Sweden.
    Iliadis, Stavros I.
    Uppsala Univ, Sweden.
    Rasmusson, Lovisa L.
    Uppsala Univ, Sweden.
    Beckman, Ulrika
    Sodra Alvsborgs Hosp, Sweden.
    Fazekas, Attila
    Lund Univ, Sweden.
    Frisén, Louise
    Karolinska Inst, Sweden.
    Sandström, Lotta
    Umea Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Wahlberg, Jeanette
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Skalkidou, Alkistis
    Uppsala Univ, Sweden.
    Papadopoulos, Fotios C.
    Uppsala Univ, Sweden.
    Preferences for Gender Affirming Treatment and Associated Factors Among Transgender People in Sweden2023Ingår i: Sexuality Research & Social Policy, ISSN 1868-9884, E-ISSN 1553-6610, Vol. 20, s. 479-490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Gender affirming surgery of primary and/or secondary sex characteristics has been shown to alleviate gender dysphoria. A descriptive snapshot of current treatment preferences is useful to understand the needs of the transgender population seeking health care. This study aimed to describe preferences for gender affirming treatment, and their correlates, among individuals seeking health care for gender dysphoria in Sweden after major national legislative reforms. Methods Cross-sectional study where transgender patients (n = 232) recruited from all six Gender Dysphoria centers in Sweden 2016-2019, answered a survey on treatment preferences and sociodemographic, health, and gender identity-related information during the same time-period. Factors associated with preferring top surgery (breast augmentation or mastectomy), genital surgery, and other surgery (e.g., facial surgery) were examined in univariable and multivariable regression analyses in the 197 people without prior such treatment. Main study outcomes were preferences for feminizing or masculinizing hormonal and surgical gender affirming treatment. Results The proportion among birth assigned male and assigned female patients preferring top surgery was 55.6% and 88.7%, genital surgery 88.9% and 65.7%, and other surgery (e.g., facial surgery) 85.6% and 22.5%, respectively. Almost all participants (99.1%) wanted or had already received hormonal treatment and most (96.7%) wished for some kind of surgical treatment; 55.0% wanted both top and genital surgery. Preferring a binary pronoun (he/she) and factors indicating more severe gender incongruence were associated with a greater wish for surgical treatment. Participants with somatic comorbidities were less likely to want genital surgery, while aF with lacking social support were less likely to want internal genital surgery, in the multivariable analyses. Conclusions In this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity. Policy Implications The study findings underline the need for individualized care and flexible gender affirming treatment options. The role of somatic comorbidities should be further explored, and support should be offered to transgender people in need. There is an unmet need for facial surgery among aM.

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  • 2.
    Baldimtsi, Evangelia
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Papadopoulou, Nektaria
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Natl & Kapodistrian Univ Athens, Greece; UNESCO Chair Adolescent Hlth Care, Greece.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Orebro Univ, Sweden.
    The role of chemokines in type 1 diabetes-associated neuropathy2023Ingår i: ENDOCRINOLOGY DIABETES & METABOLISM, ISSN 2398-9238, Vol. 6, nr 3, artikel-id e419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: To investigate whether circulating chemokines contribute to the development of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes (T1D). Methods: Fifty-two patients with childhood-onset T1D (mean age 28 +/- 4 yrs.; diabetes duration 19.5 +/- 5.5 yrs.) and 19 control subjects (mean age 26.5 +/- 4.5 yrs.) were included in a cross-sectional analysis of this long-term longitudinal cohort study. A subgroup of 24 patients was followed prospectively for a further 10 yrs. Plasma levels of Th1-(CXCL9, CXCL10 and CXCL11), Th2-(CCL17 and CCL22) and Th17-associated (CXCL8 and CCL20) chemokines were assessed in all subjects. Additionally, the TID patients underwent clinical examination and electroneurography. Results: The frequency of neuropathy was 21% (11/52). Higher levels of CXCL9 levels were found in patients with DPN compared with control subjects (p = .019); by contrast, no difference between patients without DPN and control subjects was seen after adjustment for multiple comparisons. In patients with DPN, CXCL10 correlated negatively with suralis MCV and suralis SNAP (rho -0.966, p < .001 and rho -0.738, p <.001, respectively) and was positively correlated with the vibration perception threshold (rho 0.639, p = .034), while CXCL8 correlated negatively with the cold perception threshold (rho -0.645, p = .032). The frequency of neuropathy increased to 54% (13/24) in the subgroup of 23 TID patients, followed by an additional 10 yrs. Conclusions: Changes in Th1-and Th17-associated chemokines were associated with impaired peripheral sensory nerve function and nerve conduction after long disease duration in childhood-onset T1D.

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  • 3.
    Barcenilla, Hugo
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Pihl, Mikael
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Orebro Univ, Sweden; Orebro Univ, Sweden.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Casas, Rosaura
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+CD8+T Cells in Patients With Recent-Onset Type 1 Diabetes2022Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, artikel-id 797172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naive and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD(65) only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

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  • 4.
    Bengtsson, Daniel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Department of Internal Medicine, Kalmar, Region of Kalmar County , Kalmar, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Berinder, Katarina
    Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Höybye, Charlotte
    Department of Endocrinology, Karolinska University Hospital , Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Psychotropic drugs in patients with Cushing's disease before diagnosis and at long-term follow-up - a nationwide study.2021Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, artikel-id dgab079Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment.

    OBJECTIVE: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up.

    DESIGN: Nationwide longitudinal register-based study.

    SETTING: University Hospitals in Sweden.

    SUBJECTS: CD patients diagnosed between 1990 and 2018 (N=372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed.

    MAIN OUTCOME MEASURES: Data from the Swedish Prescribed Drug Register and the Patient Register.

    RESULTS: In the 5-year period before, and at diagnosis, use of antidepressants (OR 2.2[95%CI 1.3-3.7] and 2.3[1.6-3.5]), anxiolytics (2.9[1.6-5.3] and 3.9[2.3-6.6]) and sleeping pills (2.1[1.2-3.7] and 3.8[2.4-5.9]) was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants (2.4[1.5-3.9]) and sleeping pills (3.1[1.9-5.3]). Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (IQR 8.1-10.4) had higher use of antidepressants (OR 2.0[1.1-3.8]) and sleeping pills (2.4[1.3-4.7]), but not of drugs for hypertension.

    CONCLUSIONS: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.

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  • 5.
    Bengtsson, Daniel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Department of Internal Medicine, Kalmar, Region of Kalmar County, Kalmar, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden .
    Berinder, Katarina
    Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden .
    Dahlqvist, Per
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden .
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Höybye, Charlotte
    Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden .
    Järås, Jacob
    Regional Cancer Centre, Stockholm/Gotland, Stockholm, Sweden.
    Valdemarsson, Stig
    Department of Clinical Sciences, Skåne University Hospital, University of Lund, Lund, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Faculty of Medical Sciences, Örebro University, Örebro, Sweden.
    Increased Mortality Persists after Treatment of Cushing’s Disease: A Matched Nationwide Cohort Study2022Ingår i: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Whether biochemical remission normalizes life expectancy in Cushings disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)1. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up In = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery In = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

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  • 6.
    Bergthorsdottir, R
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nilsson, A G
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gillberg, P
    Shire, Danderyd, Sweden.
    Ekman, Bertil
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Health-Related Quality of Life In Patients With Adrenal Insufficiency Receiving Plenadren Compared With Immediate-Release Hydrocortisone.2015Ingår i: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, nr 7, s. A616-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Previous studies in patients with primary adrenal insufficiency (PAI) on conventional replacement therapy suggest decreased health-related quality of life (HRQoL), and that patients report more frequently fatigue, increased anxiety and inability to work compared to background population.

    Objectives

    To study self-reported health status with EQ-5D in patients with PAI. Patients treated with Plenadren (modified-release hydrocortisone) were compared with patients treated with immediate release hydrocortisone (IRHC) replacement therapy.

    Methods

    This was a cross-sectional, multi-centre, non-interventional survey of patients with PAI receiving Plenadren or immediate release hydrocortisone (IRHC) replacement.

    Subjects

    One hundred thirty-four adult patients with PAI of whom 36 (19 females [53%]) were treated with Plenadren and 98 (77 females [79%]) were treated with IRHC, were included.

    MAIN OUTCOME MEASURE

    HRQoL described by the EQ-5D, a generic preference-based measure of health.

    RESULTS

    Patients on Plenadren and on IRHC had a mean ± SD age of 53.1 ± 12.7 years and 48.0 ± 13.1 years, respectively (P=0.043). The majority of the patients were diagnosed more than 5 years ago (69%). The mean ± SD daily Plenadren and IRHC doses were 27.0 ± 6.8 mg and 26.6 ± 10.9 mg, respectively (P=0.807). 47% of the Plenadren patients had been receiving Plenadren and 82% of the IRHC patients had been receiving IRHC for more than 3 years. Patients receiving Plenadren had better HRQoL measured by the EQ-5D questionnaire compared to patients replaced with IRHC (0.76 ± 0.18 vs 0.68 ± 0.18, respectively [P=0.040]).

    CONCLUSIONS

    Replacement therapy with Plenadren in patients with PAI confers measurable benefit on HRQoL relative to IRHC as estimated by the EQ-5D questionnaire, and may therefore be advantageous when compared to IRHC substitution.

  • 7.
    Bjorvatn Saevik, Ase
    et al.
    Univ Bergen, Norway.
    Akerman, Anna-Karin
    Orebro Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Methlie, Paal
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Quinkler, Marcus
    Endocrinol Charlottenburg, Germany.
    Palmström Jorgensen, Anders
    Oslo Univ Hosp, Norway.
    Hoybye, Charlotte
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Debowska, Aleksandra J.
    Vestfold Hosp Trust, Norway.
    Nedrebo, Bjorn Gunnar
    Univ Bergen, Norway; Haugesund Hosp, Norway.
    Dahle, Anne Lise
    Haugesund Hosp, Norway.
    Carlsen, Siri
    Stavanger Univ Hosp, Norway.
    Tomkowicz, Aneta
    Sorlandet Hosp, Norway.
    Sollid, Stina Therese
    Vestre Viken Hlth Trust, Norway.
    Nermoen, Ingrid
    Akershus Univ Hosp, Norway.
    Gronning, Kaja
    Akershus Univ Hosp, Norway.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Grimnes, Guri
    Univ Hosp North Norway, Norway; UiT Arctic Univ Norway, Norway.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Finnes, Trine
    Innlandet Hosp Trust, Norway.
    Valland, Susanna F.
    Innlandet Hosp Trust, Norway.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Holte, Synnove Emblem
    Sorlandet Hosp, Norway.
    Simunkova, Katerina
    Univ Bergen, Norway.
    Kampe, Olle
    Univ Bergen, Norway; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Husebye, Eystein Sverre
    Univ Bergen, Norway; Haukeland Hosp, Norway; Karolinska Inst, Sweden.
    Bensing, Sophie
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Oksnes, Marianne
    Univ Bergen, Norway; Haukeland Hosp, Norway; Karolinska Inst, Sweden.
    Residual Corticosteroid Production in Autoimmune Addison Disease2020Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, nr 7, s. 2430-2441Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context

    Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis.

    Objective

    To determine frequencies and clinical features of residual corticosteroid production in patients with AAD.

    Design

    Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography–tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test.

    Results

    Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = –0.487; P < 0.001).

    Conclusion

    In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.

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  • 8.
    Bothou, Christina
    et al.
    Univ Spital Zurich, Switzerland.
    Anand, Gurpreet
    Univ Spital Zurich, Switzerland.
    Li, Dingfeng
    Mayo Clin, MN 55905 USA.
    Kienitz, Tina
    Endocrinol Charlottenburg, Germany.
    Seejore, Khyatisha
    St James Univ Hosp, England.
    Simeoli, Chiara
    Univ Federico II Napoli, Italy.
    Ebbehoj, Andreas
    Aarhus Univ, Denmark.
    Ward, Emma G.
    St James Univ Hosp, England.
    Paragliola, Rosa Maria
    Univ Cattolica Sacro Cuore Fdn Policlin Univ Agos, Italy.
    Ferrigno, Rosario
    Univ Federico II Napoli, Italy.
    Badenhoop, Klaus
    Univ Hosp, Frankfurt, Germany.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden.
    Oksnes, Marianne
    Endocrinol Charlottenburg, Germany; Univ Bergen, Norway; Univ Bergen, Norway.
    Esposito, Daniela
    Univ Gothenburg, Sweden; Sahlgrenska Univ Hosp, Sweden.
    Bergthorsdottir, Ragnhildur
    Univ Gothenburg, Sweden; Sahlgrenska Univ Hosp, Sweden.
    Drake, William
    St Bartholomews Hosp, England.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Reisch, Nicole
    Klinikum Univ Munchen, Germany.
    Hahner, Stefanie
    Univ Wurzburg, Germany.
    Pearce, Simon
    Newcastle Univ, England.
    Trainer, Peter
    Christie NHS Fdn, England.
    Etzrodt-Walter, Gwendolin
    Praxis Dr Etzrodt Walter Endokrinol Zentrum Ulm, Germany.
    Thalmann, Sebastien P.
    Arztezentrum Sihlcity, Switzerland.
    Saevik, Ase B.
    Univ Bergen, Norway.
    Husebye, Eystein
    Univ Bergen, Norway.
    Isidori, Andrea M.
    Sapienza Univ Rome, Italy.
    Falhammar, Henrik
    Karolinska Univ Hosp, Sweden.
    Meyer, Gesine
    Univ Hosp, Germany.
    Corsello, Salvatore M.
    Univ Cattolica Sacro Cuore Fdn Policlin Univ Agos, Italy.
    Pivonello, Rosario
    Univ Federico II Napoli, Italy.
    Murray, Robert
    St James Univ Hosp, England.
    Bancos, Irina
    Mayo Clin, MN 55905 USA.
    Quinkler, Marcus
    Endocrinol Charlottenburg, Germany.
    Beuschlein, Felix
    Univ Spital Zurich, Switzerland; Klinikum Univ Munchen, Germany.
    Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey2020Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, nr 8, s. E2853-E2863Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context

    Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment.

    Objective

    Multicenter survey on current clinical approaches in managing AI during pregnancy.

    Design

    Retrospective anonymized data collection from 19 international centers from 2013 to 2019.

    Setting and Patients

    128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%).

    Results

    Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes.

    Conclusions

    This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

  • 9.
    Burman, P
    et al.
    Skånes University Hospital Malmö Lund, Sweden .
    Mattsson, A F
    Pfizer Health AB, Sweden .
    Johannsson, G
    University of Gothenburg, Sweden .
    Hoybye, C
    Karolinska University Hospital, Sweden .
    Holmer, H
    Central Hospital Kristianstad, Sweden .
    Dahlqvist, P
    Umeå University, Sweden .
    Berinder, K
    Karolinska University Hospital, Sweden .
    Engstrom, B E
    Uppsala University, Sweden .
    Ekman, Bertil
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Erfurth, E M.
    Skånes University Hospital Malmö Lund, Sweden .
    Svensson, J
    University of Gothenburg, Sweden .
    Wahlberg, J
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Karlsson, F A
    Uppsala University, Sweden .
    Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality2013Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, nr 4, s. 1466-1475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. less thanbrgreater than less thanbrgreater thanObjective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. less thanbrgreater than less thanbrgreater thanDesign and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. less thanbrgreater than less thanbrgreater thanResults: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. less thanbrgreater than less thanbrgreater thanConclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease. (J Clin Endocrinol Metab 98: 1466-1475, 2013)

  • 10.
    Burman, Pia
    et al.
    Lund University, Sweden.
    Eden-Engstrom, Britt
    Uppsala University, Sweden.
    Ekman, Bertil
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Anders Karlsson, F.
    Uppsala University, Sweden.
    Schwarcz, Erik
    University of Örebro, Sweden.
    Wahlberg Topp, Jeanette
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Limited value of cabergoline in Cushings disease: a prospective study of a 6-week treatment in 20 patients2016Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, nr 1, s. 17-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context and objective: The role of cabergoline in Cushings disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after &gt;= 1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Design: Twenty patients (19 naive and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Methods: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. Results: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a &gt;50% decrease of UFC, three had a &gt;50% rise of UFC. Salivary cortisol at 2300 h showed a congruent &gt;50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Conclusions: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

  • 11.
    Bäcklund, Nils
    et al.
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Brattsand, Göran
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Israelsson, Marlen
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Ragnarsson, Oskar
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden.
    Edén Engström, Britt
    Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden.
    Høybye, Charlotte
    Department of Molecular Medicine and Surgery, Patient Area Endocrinology and Nephrology, Inflammation and Infection Theme, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Berinder, Katarina
    Department of Molecular Medicine and Surgery, Patient Area Endocrinology and Nephrology, Inflammation and Infection Theme, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Olsson, Tommy
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Dahlqvist, Per
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushings syndrome2020Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 182, nr 6, s. 569-582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The challenge of diagnosing Cushings syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).

  • 12.
    Bélteky, Malin
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Maternal respiratory infections in early pregnancy increases the risk of type 1 diabetes2020Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 21, nr 7, s. 1193-1201Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Objective

    Is exposure to maternal infections and use of antibiotics in the prenatal period associated with increased risk of T1D, regardless of genetic risk? Methods Data on infections and use of antibiotics during pregnancy were collected from questionnaires at birth from parents to 16 292 children in the All Babies in Southeast Sweden (ABIS) cohort and validated against national diagnosis registers. As of November 2017, 137 ABIS children had developed T1D, 72 boys and 65 girls (0.8% of the original cohort).

    Results

    More cases were born in spring and summer than fall and winter. However, onset of T1D appeared to be more common in either summer or winter. In univariate analyses, respiratory tract infection in the first trimester (P= .002) and gastroenteritis during pregnancy (P= .04) were associated with later risk of T1D in the offspring. Other types of infection or antibiotic treatment were not associated with an increased risk. In a multiple logistic regression model, a mother with an autoimmune disease (P &lt; .001), father with T1D (P &lt; .001) and respiratory tract infection during the first trimester (P= .005) remained as risk factors for T1D in the offspring. In children with neutral HLA alleles antibiotic treatment may increase the risk of T1D (P= .01, OR 3.46, 95% CI 1.25-9.55).

    Conclusions

    In the general population there seems to be an association between seasonal maternal respiratory tract infection in the first trimester of pregnancy and later risk of T1D in the offspring. HLA may play a role for the effect of exposure to infections and antibiotics.

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  • 13.
    Casas, Rosaura
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Dietrich, Fabricia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Barcenilla, Hugo
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Tavira Iglesias, Beatriz
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Achenbach, Peter
    Helmholtz Zentrum Munchen, Germany; Tech Univ Munich, Germany.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients2020Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, artikel-id 564921Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 mu g GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD(65)-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC &lt; 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8(+) T cells activation. Patients with poorer clinical response had higher baseline levels of GAD(65-)induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment.

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  • 14.
    Casas, Rosaura
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Dietrich, Fabricia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Puente Marin, Sara
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Barcenilla, Hugo
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Tavira Iglesias, Beatriz
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Achenbach, Peter
    Tech Univ Munich, Germany.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Intra-lymphatic administration of GAD-alum in type 1 diabetes: long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial)2022Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, s. 687-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim To evaluate the long-term effect of intra-lymphatic administration of GAD-alum and a booster dose 2.5 years after the first intervention (DIAGNODE Extension study) in patients with recent-onset type 1 diabetes. Methods DIAGNODE-1: Samples were collected from 12 patients after 30 months who had received 3 injections of 4 mu g GAD-alum into a lymph node with one-month interval. DIAGNODE Extension study: First in human, a fourth booster dose of autoantigen (GAD-alum) was given to 3 patients at 31.5 months, who were followed for another 12 months. C-peptide was measured during mixed meal tolerance tests (MMTTs). GADA, IA-2A, GADA subclasses, GAD(65)-induced cytokines, PBMCs proliferation and T cells markers were analyzed. Results After 30-month treatment, efficacy was still seen in 8/12 patients (good responders, GR). Partial remission (IDAA1c &lt; 9) had decreased compared to 15 months, but did not differ from baseline, and HbA1c remained stable. GAD(65)-specific immune responses induced by the treatment started to wane after 30 months, and most changes observed at 15 months were undetectable. GADA subclasses IgG2, IgG3 and IgG4 were predominant in the GR along with IgG1. A fourth intra-lymphatic GAD-alum dose to three patients after 31.5 months gave no adverse events. In all three patients, C-peptide seemed to increase the first 6 months, and thereafter, C-peptide, HbA1c, insulin requirement and IDAA1c remained stable. Conclusion The effect of intra-lymphatic injections of GAD-alum had decreased after 30 months. Good responders showed a specific immune response. Administration of a fourth booster dose after 31.5 months was safe, and there was no decline in C-peptide observed during the 12-month follow-up.

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  • 15.
    Dahlqvist, Per
    et al.
    Norrlands Universitetssjukhus, Umeå .
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna .
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg .
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska sjukhuset, Göteborg .
    Hulting, Anna-Lena
    Karolinska universitetssjukhuset, Solna .
    [A national medical emergency card for adrenal insufficiency. A new warning card for better management and patient safety].2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 44, s. 2226-2227Artikel i tidskrift (Övrigt vetenskapligt)
  • 16.
    Dahlqvist, Per
    et al.
    Norrlands ­universitetssjukhus, Umeå.
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna.
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska universitetssjukhuset, Göteborg.
    Hulting, Anna-Lena
    Karolinska universitetssjukhuset, Solna.
    Nationellt kort vid binjurebarkssvikt: Nytt varningskort kan leda till bättre handläggning och ökad patientsäkerhet2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 44, s. 2226-2227Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Akut binjurebarkssvikt ­(akut kortisolbrist/Addisonkris) är en ovanlig men viktig differentialdiagnos vid akut cirkulationssvikt.

    De flesta fall av Addisonkris drabbar patienter med känd binjurebarkssvikt, oftast i samband med gastroenterit eller annan infektion.

    Noggrann och tydlig information och utbildning av ­patienter, anhöriga och sjukvårdspersonal behövs för att undvika sjuklighet och dödsfall i akut binjurebarkssvikt.

    Ett nationellt varningskort i kreditkortsformat har tagits fram till patienter med bi­njurebarkssvikt för att uppmärksamma och förbättra handläggningen av detta potentiellt livshotande tillstånd.

  • 17.
    Dalin, Frida
    et al.
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Nordling Eriksson, Gabriel
    Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten.
    Ekwall, Olov
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Söderberg, Stefan
    Umeå University, Umeå, Sweden.
    Rönnelid, Johan
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olcén, Per
    Örebro University, Örebro, Sweden.
    Winqvist, Ola
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Kriström, Berit
    Umeå University, Umeå, Sweden.
    Laudius, Maria
    Umeå University, Umeå, Sweden.
    Isaksson, Magnus
    Uppsala University, Uppsala, Sweden.
    Halldin Stenlid, Maria
    Uppsala University, Uppsala, Sweden.
    Gustafsson, Jan
    Uppsala University, Uppsala, Sweden.
    Gebre-Medhin, Gennet
    Uppsala University, Uppsala, Sweden.
    Björnsdottir, Sigridur
    Karolinska In Karolinska University Hospital, Stockholm, Sweden.
    Janson, Annika
    Karolinska Institutet, Stockholm, Sweden.
    Åkerman, Anna-Karin
    Örebro University, Örebro, Sweden.
    Åman, Jan
    Örebro University, Örebro, Sweden.
    Duchen, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johannsson, Gudmundur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lindskog, Emma
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Skåne University Hospital, Malmö, Sweden..
    Elfving, Maria
    Lund University, Lund, Sweden..
    Waldenström, Erik
    Skåne University Hospital, Malmö, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study.2017Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, nr 2, s. 379-389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 18.
    Dietrich, Fabricia
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Barcenilla, Hugo
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Tavira Iglesias, Beatriz
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Faculty of Medical Sciences, Örebro University, Örebro, Sweden.
    Achenbach, Peter
    Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Casas, Rosaura
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset type 1 diabetes2022Ingår i: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 38, nr 3, artikel-id e3500Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for type 1 diabetes (T1D). Studies with GAD-alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD-alum into the lymph nodes, aimed to optimise antigen presentation, has shown promising results in an open-label clinical trial. Herein, we compared the immune response of the individuals included in the trial with a group who received GAD-alum subcutaneously in a previous study.

    Materials and methods: Samples from T1D individuals collected 15 months after administration of either three doses 1 month apart of 4 mu g GAD-alum into lymph nodes (LN, n = 12) or two doses 1 month apart of 20 mu g subcutaneously (SC, n = 12) were studied. GADA, GADA subclasses, GAD(65)-induced cytokines, peripheral blood mononuclear cell proliferation, and T cells markers were analysed.

    Results: Low doses of GAD-alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterised by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3, and IgG4 proportion, higher GAD(65)-induced secretion of IL-5, IL-10, and TNF-alpha, and reduction of cell proliferation and CD8(+) T cells. These changes were not observed after subcutaneous (SC) injections of GAD-alum.

    Conclusions: GAD-specific immune responses 15 months after lymph node injections of GAD-alum differed from the ones induced by SC administration of the same autoantigen.

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  • 19.
    Ekman, Bertil
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Alstrand, N
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet. County Hospital, Kalmar .
    Bachrach-Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life2014Ingår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 46, nr 1, s. 48-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adrenalitis found in autoimmune Addison’s disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.

    Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33–56) pg/ml vs. 22 (19–34) pg/ml, p<0.01] and CXCL11 [37 (29–48) pg/ml vs. 16 (9–24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life.

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  • 20.
    Ekman, Bertil
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Bachrach-Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Blomgren, Johan
    Internal Medicine County Hospital, Eksjö.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    A randomised double blind crossover study comparing two and four dose hydrocortisone regimen with regard to quality for life, cortisol and ACTH profiles in patients with primary adrenal insufficiency2012Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 1, s. 18-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context

    Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data.

    Objective

    To assess how an equal dose of hydrocortisone given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH, patient preferences and health related quality of life (HRQoL).

    Design

    Double blind, crossover.

    Methods

    Fifteen patients with PAI (6 women) were included. Capsules of hydrocortisone or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4-week treatment periods: either one period with four doses (10+10+5+5 mg) or one period with two doses (20+0+10+0 mg). Diurnal profiles of cortisol and ACTH were collected and area under the curve (AUC) was calculated. Questionnaires were used to evaluate patient preferences and HRQoL.

    Results

    The four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0.027) and a higher 24-h-cortisolAUC (P < 0.0001) compared with the two-dose period. In contrast a lower median plasma ACTH in the morning before tablet intake (P = 0.003) and a lower 24-h-ln(ACTHAUC) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0.03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period.

    In summary a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive.

  • 21.
    Ekman, Bertil
    et al.
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Wahlberg Topp, Jeanette
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Landberg, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Urine oligosaccharide pattern in patients with hyperprolactinaemia2015Ingår i: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 32, nr 8, s. 635-641Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Free milk-type oligosaccharides are produced during pregnancy and lactation and may have an impact on several cells in the immune system. Our aim was to investigate if patients with isolated hyperprolactinaemia, not related to pregnancy, also have increased synthesis and urinary excretion of milk-type oligosaccharides and to compare the excretion pattern with that found during pregnancy. Urine samples were collected as morning sample from 18 patients with hyperprolactinaemia, 13 healthy controls with normal prolactin levels and four pregnant women. After purification, lactose and free oligosaccharides were analysed and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection. The identity of peaks was confirmed by exoglycosidase treatment and comparison with oligosaccharide standards. Prolactin was measured in serum collected between 09 and 11 a.m. by a standardized immunochemical method. Patients with hyperprolactinaemia had higher urinary excretion of lactose than normoprolactinemic controls and urinary lactose correlated positively to prolactin levels (r = 0.51, p less than 0.05). Increased levels of the fucosylated oligosaccharides 2-fucosyl lactose and lacto-di-fucotetraose were found in urine from three and two patients, respectively. The acidic oligosaccharide 3-sialyl lactose was found in high amount in urine from two patients with prolactin of greater than 10,000 mU/l. However, pregnant women in their third trimester had the highest concentration of all these oligosaccharides and excretion increased during pregnancy. This study is first to show that both lactose and certain fucosylated and sialylated milk-type oligosaccharides are increased in some patients with hyperprolactinaemia. It remains to elucidate the functional importance of these findings.

  • 22.
    Eriksson, D.
    et al.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden.
    Bianchi, M.
    Uppsala University, Sweden.
    Landegren, N.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Nordin, J.
    Uppsala University, Sweden.
    Dalin, F.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Mathioudaki, A.
    Uppsala University, Sweden.
    Eriksson, G. N.
    Karolinska Institute, Sweden.
    Hultin-Rosenberg, L.
    Uppsala University, Sweden.
    Dahlqvist, J.
    Uppsala University, Sweden.
    Zetterqvist, H.
    Uppsala University, Sweden; Uppsala University, Sweden.
    Karlsson, A.
    Uppsala University, Sweden.
    Hallgren, A.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Farias, F. H. G.
    Uppsala University, Sweden.
    Muren, E.
    Uppsala University, Sweden.
    Ahlgren, K. M.
    Uppsala University, Sweden.
    Lobell, A.
    Uppsala University, Sweden.
    Andersson, G.
    Swedish University of Agriculture Science, Sweden.
    Tandre, K.
    Uppsala University, Sweden.
    Dahlqvist, S. R.
    Umeå University, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rönnblom, L.
    Uppsala University, Sweden.
    Hulting, A. -L.
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Ekwall, O.
    University of Gothenburg, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Meadows, J. R. S.
    Uppsala University, Sweden.
    Bensing, S.
    Metab and Diabet Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lindblad-Toh, K.
    Uppsala University, Sweden; Broad Institute MIT and Harvard, MA USA.
    Kampe, O.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden; Uppsala University, Sweden.
    Pielberg, G. R.
    Uppsala University, Sweden.
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addisons disease2016Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, nr 6, s. 595-608Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addisons disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addisons disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addisons disease, we have identified BACH2 as a major risk locus in Addisons disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

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  • 23.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Dalin, Frida
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala Univ, Sweden.
    Mathioudaki, Argyri
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Andersson, Goran
    Swedish Univ Agr Sci, Sweden.
    Tandre, Karolina
    Uppsala Univ, Sweden.
    Rantapaa Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT and Harvard, MA USA.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Kampe, Olle
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; KG Jebsen Ctr Autoimmune Dis, Norway.
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addisons disease in Sweden2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 8395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

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  • 24.
    Eriksson, Daniel
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Dalin, Frida
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Eriksson, Gabriel Nordling
    Karolinska Institutet, Stockholm, Sweden.
    Landegren, Nils
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Bianchi, Matteo
    Uppsala University, Uppsala, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Ekwall, Olov
    Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Winqvist, Ola
    Karolinska Institutet, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala University, Uppsala, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Uppsala, Sweden, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
    Alimohammadi, Mohammad
    Uppsala University, Uppsala, Sweden.
    Husebye, Eystein S
    Karolinska Institutet, Stockholm, University of Bergen, Bergen, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Knappskog, Per Morten
    University of Bergen, Bergen, Haukeland University Hospital, Bergen, Norway.
    Rosengren Pielberg, Gerli
    Uppsala University, Uppsala, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Uppsala University, Uppsala, Sweden, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.2018Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 1, s. 179-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

  • 25.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Uppsala Univ Hosp, Sweden; Uppsala Univ, Sweden.
    Royrvik, Ellen Christine
    Univ Bergen, Norway; Univ Bergen, Norway.
    Aranda-Guillen, Maribel
    Karolinska Inst, Sweden.
    Berger, Amund Holte
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Artaza, Haydee
    Univ Bergen, Norway.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Grytaas, Marianne Aardal
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Strom, Sara
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bratland, Eirik
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Botusan, Ileana Ruxandra
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Oftedal, Bergithe Eikeland
    Univ Bergen, Norway; Univ Bergen, Norway.
    Breivik, Lars
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Vaudel, Marc
    Univ Bergen, Norway.
    Helgeland, Oyvind
    Univ Bergen, Norway; Inst Publ Hlth, Norway.
    Falorni, Alberto
    Univ Perugia, Italy.
    Jorgensen, Anders Palmstrom
    Oslo Univ Hosp, Norway.
    Hulting, Anna-Lena
    Karolinska Inst, Sweden.
    Svartberg, Johan
    UiT Arctic Univ Norway, Norway; Univ Hosp North Norway, Norway.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Fougner, Kristian Johan
    St Olavs Hosp, Norway.
    Wahlberg, Jeanette
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Nedrebo, Bjorn Gunnar
    Univ Bergen, Norway; Haugesund Hosp, Norway.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Knappskog, Per Morten
    Univ Bergen, Norway; Univ Bergen, Norway; Haukeland Hosp, Norway.
    Wolff, Anette Susanne Boe
    Univ Bergen, Norway; Univ Bergen, Norway.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Johansson, Stefan
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Kampe, Olle
    Karolinska Inst, Sweden; Univ Bergen, Norway; Univ Bergen, Norway; Karolinska Univ Hosp, Sweden.
    Husebye, Eystein Sverre
    Karolinska Inst, Sweden; Univ Bergen, Norway; Univ Bergen, Norway; Haukeland Hosp, Norway.
    GWAS for autoimmune Addisons disease identifies multiple risk loci and highlights AIRE in disease susceptibility2021Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 12, nr 1, artikel-id 959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P&lt;5x10(-8)). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR=3.4 (2.7-4.3), P=9.0x10(-25)) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h(2)). Autoimmune Addisons disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

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  • 26.
    Ernersson, Åsa
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten.
    Bachrack Lindström, Margareta
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten.
    Landberg, Eva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Orebro Univ, Sweden.
    Reduced Health Related Quality of Life, Increased Fatigue, and Daytime Sleepiness in Women with Hyperprolactinemia2023Ingår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 55, nr 4, s. 266-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prolactin has many physiological effects and seems to be involved in the human quality of life and well- being. The aim of this study was to describe health related quality of life, fatigue and daytime sleepiness in women with untreated hyperprolactinemia. In total 32 women (mean age 37.0 +/- 10.9 years) with verified hyperprolactinemia completed a questionnaire including questions on fatigue, measured with the Swedish version of the Fatigue Impact Scale ( FIS), propensity to fall in sleep, measured with the Swedish version of the Epworth Sleepiness Scale (ESS), and Health related quality of life (HRQoL), measured by the Short-Form- 36 scale ( SF-36). For comparison Swe-dish normative data were used. The women were also interviewed regarding different symptoms related to hyperprolactinemia and the answers were analyzed using qualitative content analysis. HRQoL, as measured with SF-36, was significantly lower in all dimensions, except in physical function, compared to the Swedish reference population. Total FIS was 54.3 (41.1) and mean score on the ESS was 8.7 (4.2) indicating increased fatigue and deterioration in night sleep. The women felt very tired, and several of them rarely felt rested in the morning. The restless night sleep and the fatigue during the daytime got them to feel feeble and sometimes to find it difficult to concentrate, which affected both their mood and life in general. Women diagnosed with hyperprolactinemia reported deterioration in night sleep, increased rate of fatigue, and a reduced health related quality of life in comparison with the reference population.

  • 27.
    Espiard, Stéphanie
    et al.
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    McQueen, Johanna
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Sherlock, Mark
    Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Co. Dublin 9, Ireland..
    Ragnarsson, Oskar
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Bergthorsdottir, Ragnhildur
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Burman, Pia
    Department of Endocrinology, Skåne University Hospital Malmö, Malmö and University of Lund, Lund, Sweden..
    Dahlqvist, Per
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden..
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Engström, Britt Edén
    Department of Medical Sciences, Endocrinology and Metabolism, Uppsala University Hospital, Uppsala, Sweden..
    Skrtic, Stanko
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.AstraZeneca R&D, Mölndal, Sweden..
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Stewart, Paul M
    Faculty of Medicine and Health, University of Leeds, Leeds, UK..
    Johannsson, Gudmundur
    Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone2021Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, nr 3, s. 814-825Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.

    OBJECTIVE: This work aimed to study cortisol metabolism during DR-HC and TID-HC.

    DESIGN: A randomized, 12-week, crossover study was conducted.

    INTERVENTION AND PARTICIPANTS: DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls.

    MAIN OUTCOME MEASURES: Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.

    RESULTS: Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < .001) and reached control values (P = .089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < .05), but remained increased vs controls (P < .001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC vs controls (P < .01) but normalized with DR-HC (P = .358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.

    CONCLUSIONS: The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change toward normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.

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  • 28.
    Ewerman, Lea
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Landberg, Eva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Hellberg, Sandra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Hovland, Mina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Sundin, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia2020Ingår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 52, nr 4, s. 228-235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p&lt;0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (&gt;3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation.

  • 29.
    Gullstrand, Camilla
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Ilonen, Jorma
    Dept of Microbiology Kuopio, Finland.
    Vaarala, Outi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study2008Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, nr 3 PART 1, s. 182-190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.

  • 30.
    Hirschberg, Daniel
    et al.
    Umea Univ, Sweden.
    Ekman, Bertil
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Wahlberg, Jeanette
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Landberg, Eva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Altered immunoglobulin G glycosylation in patients with isolated hyperprolactinaemia2021Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 16, nr 2, artikel-id e0247805Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prolactin is a peptide hormone produced in the anterior pituitary, which increase in several physiological and pathological situations. It is unclear if hyperprolactinaemia may affect glycosylation of immunoglobulin G (IgG). Twenty-five patients with hyperprolactinemia and 22 healthy control subjects were included in the study. The groups had similar age and gender distribution. A panel of hormonal and haematological analyses, creatinine, glucose, liver enzymes and immunoglobulins were measured by routine clinical methods. IgG was purified from serum by Protein G Sepharose. Sialic acid was released from IgG by use of neuraminidase followed by quantification on high performance anion-exchange chromatography with pulsed amperometric detection. Tryptic glycopeptides of IgG was analysed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Hormone and immunoglobulin levels were similar in the two groups, except for IgA and prolactin. Significantly higher IgG1 and IgG2/3 galactosylation was found in the patient group with hyperprolactinaemia compared to controls. (A significant correlation between prolactin and IgG2/3 galactosylation (Rs 0.61, p&lt;0.001) was found for samples with prolactin values below 2000 mIU/L. The relative amount of sialylated and bisecting glycans on IgG did not differ between patients and controls. The four macroprolactinaemic patients showed decreased relative amount of bisecting IgG2/3 glycans. Hyperprolactinaemia was found to be associated with increased galactosylation of IgG1 and IgG2/3. This may have impact on IgG interactions with Fc-receptors, complement and lectins, and consequently lead to an altered immune response.

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  • 31.
    Holmberg, Hanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Wahlberg (Topp), Jeanette
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Vaarala, Outi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population2007Ingår i: British Journal of Nutrition, ISSN 0007-1145, Vol. 97, nr 1, s. 111-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and β-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2-09, 95% CI 1-45, 3-02; P<0-000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2-89, 95% CI 1-81, 4-62; P<0-000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2-01, 95% CI 1-08, 3-73; P = 0-028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3-50, 95% CI 1-38, 8-92; P = 0-009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1-84, 95% CI 1-01, 3-37; P = 0-047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for β-cell autoantibodies in children from the general population suggests that breast-feeding modifies the risk of β-cell autoimmunity, even years after finishing breast-feeding.

  • 32.
    Hyllienmark, Lars
    et al.
    Karolinska Institute, Sweden .
    Alstrand, Nils
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Jonsson, Bjorn
    Uppsala University, Sweden .
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Cooray, Gerald
    Karolinska Institute, Sweden .
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes2013Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 10, s. 3187-3194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.

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  • 33.
    Iliadis, Stavros I.
    et al.
    Uppsala Univ, Sweden.
    Axfors, Cathrine
    Uppsala Univ, Sweden.
    Friberg, Agnes
    Uppsala Univ, Sweden.
    Arinell, Hans
    Uppsala Univ, Sweden.
    Beckman, Ulrika
    Sodra Alvsborgs Hosp, Sweden.
    Fazekas, Attila
    Lund Univ, Sweden.
    Frisen, Louise
    Karolinska Inst, Sweden.
    Sandstroem, Lotta
    Umea Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Sodersten, Maria
    Karolinska Inst, Sweden.
    Papadopoulos, Fotios C.
    Uppsala Univ, Sweden.
    Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 18701Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n=135) and controls (n=443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.

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  • 34.
    Johannsson, G
    et al.
    Sahlgrens University Hospital.
    Nilsson, A G
    Sahlgrens University Hospital.
    Bergthorsdottir, R
    Sahlgrens University Hospital.
    Burman, P A
    Malmo University Hospital.
    Eden Engstrom, B
    Uppsala University Hospital.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Dahlqvist, P
    Umea University Hospital.
    Ryberg, M
    Umea University Hospital.
    Ragnarsson, O
    Sahlgrens University Hospital.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lennernas, H
    Uppsala University.
    Skrtic, S
    Sahlgrens University Hospital.
    Improved Quality of Life in Patients with Primary Adrenal Insufficiency by Using a Novel Once-Daily Dual Release Hydrocortisone Tablet: A Randomised Controlled, Cross-Over Trial. in ENDOCRINE REVIEWS, vol 31, issue 3, pp2010Ingår i: ENDOCRINE REVIEWS, Endocrine Society , 2010, Vol. 31, nr 3Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 35.
    Johansson, G.
    et al.
    Sahlgrenska Academy, University of Gothenburg.
    Nilsson, A. G.
    Sahlgrenska Academy, University of Gothenburg.
    Bergthorsdottir, R.
    Sahlgrenska Academy, University of Gothenburg.
    Burman, P.
    Skånes University Hospital, Malmö.
    Dahlqvist, P.
    Umeå University.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Engström, B. E
    Uppsala University.
    Olsson, T.
    Umeå University.
    Ragnarsson, O.
    Sahlgrenska Academy, University of Gothenburg.
    Ryberg, M.
    Umeå University.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Biller, B. M. K.
    Massachusetts General Hospital, Harvard Medical School, Boston.
    Monson, J. P.
    St. Bartholomew's Hospital, Queen Mary University of London.
    Stewart, P. M.
    University of Birmingham.
    Lennernäs, H.
    Uppsala University.
    Skrtic, S.
    Sahlgrenska Academy, University of Gothenburg.
    Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomised trial of a novel hydrocortisone dual-release formulation2012Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, nr 2, s. 473-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.

    Objective: The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.

    Design and Setting: We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.

    Patients: The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).

    Intervention: The same daily dose of hydrocortisone was administered as OD dual-release or TID.

    Main Outcome Measure: We evaluated cortisol pharmacokinetics.

    Results: Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).

    Conclusion: The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

  • 36.
    Landberg, Eva
    et al.
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Rydén, Ingvar
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Arvidsson, Britt-Marie
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration2007Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, nr 1-2, s. 220-225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.

    Methods

    A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.

    Results

    The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.

    Conclusions

    Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.

  • 37.
    Landegren, Nils
    et al.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Sharon, Donald
    Stanford University, CA 94305 USA; Yale University, CT 06520 USA.
    Freyhult, Eva
    Uppsala University, Sweden; Uppsala University, Sweden.
    Hallgren, Asa
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Eriksson, Daniel
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Edqvist, Per-Henrik
    Uppsala University, Sweden; Science Life Lab, Sweden.
    Bensing, Sophie
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Nelson, Lawrence M.
    NICHHD, MD 20892 USA.
    Gustafsson, Jan
    Uppsala University, Sweden.
    Husebye, Eystein S.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Anderson, Mark S.
    University of Calif San Francisco, CA 94143 USA.
    Snyder, Michael
    Stanford University, CA 94305 USA.
    Kampe, Olle
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 12016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, nr 20104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIREs selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

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  • 38.
    Lethin, Kajsa
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Aardal, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lood, Yvonne
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Orebro Univ, Sweden.
    Effects of 12 Months' Treatment with Testosterone Undecanoate on Markers for Erythropoietic Activity and Safety Aspects in Transgender and Cisgender Hypogonadal Men2023Ingår i: The Journal of Applied Laboratory Medicine, ISSN 2576-9456, E-ISSN 2475-7241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background To investigate the erythropoietic activity and safety aspects of testosterone undecanoate (TU) injections in transgender men, assigned female at birth.Methods Twenty-three men (13 hypogonadal cisgender men and 10 transgender men) who initiated TU at the study start (naive) and 15 men (10 hypogonadal cisgender men and 5 transgender men) on steady-state treatment with TU (non-naive) were included in this prospective 1-year observational study. A control group of 32 eugonadal cisgender men was investigated once at baseline. Complete blood count, testosterone in serum and saliva, and plasma lipids, and liver enzymes were assessed.Results For naive transgender men, a significant increase in hemoglobin concentration was noted (mean (SD)), 141 (8) g/L to 151 (13) g/L, while no increase was seen in naive hypogonadal cisgender men. At the end of the study, naive transgender men exhibited comparable levels of hemoglobin, hematocrit, and testosterone levels in serum and saliva to hypogonadal cisgender men, as well as to the eugonadal cisgender men. During the study, HDL-cholesterol decreased significantly in naive transgender men, 1.4 (0.4) mmol/L to 1.2 (0.4) mmol/L, P = 0.03, whereas no significant change was noted in naive hypogonadal cisgender men. Liver enzymes remained unchanged in all groups.Conclusions After 12 months of treatment with TU in naive transgender men, hemoglobin and hematocrit increased to levels within the cisgender male reference range. A slight decrease in HDL-cholesterol was seen in naive transgender men but liver enzymes remained unchanged.

  • 39.
    Lood, Yvonne
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Aardal, Elisabeth
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi.
    Ahlner, Johan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten.
    Ärlemalm, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Carlsson, Björn
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi.
    Ekman, Bertil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. National Forensic Centre, Linköping, Sweden.
    Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: An accurate and sensitive method applied on clinical and forensic samples2021Ingår i: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 195, artikel-id 113823Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC–MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4−1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99–101 % and 93–95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.

  • 40.
    Lood, Yvonne
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
    Aardal-Eriksson, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Webe, C.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism2018Ingår i: Andrology, ISSN 2047-2919, E-ISSN 2047-2927, Vol. 6, nr 1, s. 86-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Long-term testosterone replacement therapy is mainly monitored by trough levels of serum testosterone (S-T), while urinary testosterone (U-T) is used by forensic toxicology to evaluate testosterone doping. Testosterone in saliva (Sal-T) may provide additional information and simplify the sample collection. We aimed to investigate the relationships between testosterone measured in saliva, serum and urine during standard treatment with 1,000mg testosterone undecanoate (TU) every 12th week during 1year. This was an observational study. Males with primary and secondary hypogonadism (HG; n=23), subjects with gender dysphoria (GD FtM; n=15) and a healthy control group of men (n=32) were investigated. Sal-T, S-T and U-T were measured before and after TU injections. Sal-T was determined with Salimetrics((R)) enzyme immunoassay, S-T with Roche Elecsys((R)) testosterone II assay and U-T by gas chromatography-mass spectrometry. Sal-T correlated significantly with S-T and calculated free testosterone in both controls and patients (HG men and GD FtM), while Sal-T to U-T showed weaker correlations. Trough values of Sal-T after 12months were significantly higher in the GD FtM group (0.77 +/- 0.35nmol/L) compared to HG men (0.53 +/- 0.22nmol/L) and controls (0.46 +/- 0.15nmol/L), while no differences between S-T and U-T trough values were found. Markedly elevated concentrations of salivary testosterone, 7-14days after injection, were observed, especially in the GD FtM group. This study demonstrates that Sal-T might be a useful clinical tool to monitor long-term testosterone replacement therapy and might give additional information in forensic cases.

  • 41.
    Ludvigsson, Johnny
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Sumnik, Zdenek
    Charles Univ Prague, Czech Republic.
    Pelikanova, Terezie
    Inst Clin & Expt Med, Czech Republic.
    Nattero Chavez, Lia
    Hosp Univ Ramon & Cajal, Spain.
    Lundberg, Elena
    Umea Univ, Sweden.
    Rica, Itxaso
    Cruces Univ Hosp, Spain.
    Martinez-Brocca, Maria A.
    Virgen Macarena Hosp, Spain.
    Ruiz de Adana, Marisol
    Gen Univ Hosp, Spain.
    Wahlberg, Jeanette
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Katsarou, Anastasia
    Skane Univ Hosp, Sweden.
    Hanas, Ragnar
    NU Hosp Grp, Sweden.
    Hernandez, Cristina
    Vall dHebron Hosp, Spain.
    Clemente Leon, Maria
    Vall dHebron Hosp, Spain.
    Gomez-Gila, Ana
    Virgen Roc Univ Hosp, Spain.
    Lind, Marcus
    Univ Gothenburg, Sweden; Dept Med, Sweden.
    Lozano, Marta Ferrer
    Miguel Servet Univ Hosp, Spain.
    Sas, Theo
    Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    Samuelsson, Ulf
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Pruhova, Stepanka
    Charles Univ Prague, Czech Republic; Motol Univ Hosp, Czech Republic.
    Dietrich, Fabricia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Puente Marin, Sara
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Nordlund, Anders
    Trial Form Support, Sweden.
    Hannelius, Ulf
    Diamyd Med AB, Sweden.
    Casas, Rosaura
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial2021Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, nr 7, s. 1604-1612Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide &gt;0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) &lt;= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.

  • 42.
    Ludvigsson, Johnny
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old2002Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, s. 289-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoantibodies found in cord blood in children who later develop diabetes might be produced by the fetus. If so, continuous autoantibody production would still be expected in these children at one year of age. We decided to determine autoantibodies in cord blood and to see whether they persisted in these children at one year. Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). Information on infections during pregnancy was available in 2,169 pregnancies. In the autoantibody-positive group, 31.5% had an infection during pregnancy, which was more common than in the autoantibody-negative group of 500 children with the lowest values (20.1%; P < 0.04). At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. We conclude that most autoantibodies found in cord blood samples of children are probably passively transferred from mother to child. Antibody screening of cord blood cannot be used to predict diabetes in the general population. Infections during pregnancy may initiate an immune process related to diabetes development.

  • 43.
    Ludvigsson, Johnny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Casas, Rosaura
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Letter: Intralymphatic Injection of Autoantigen in Type 1 Diabetes in NEW ENGLAND JOURNAL OF MEDICINE, vol 376, issue 7, pp 697-6992017Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, nr 7, s. 697-699Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

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  • 44.
    Mitchell, Anna L.
    et al.
    Newcastle University, England .
    Macarthur, Katie D. R.
    Newcastle University, England .
    Gan, Earn H.
    Newcastle University, England .
    Baggott, Lucy E.
    Newcastle University, England .
    Wolff, Anette S. B.
    University of Bergen, Norway .
    Skinningsrud, Beate
    Oslo University Hospital, Norway University of Oslo, Norway .
    Platt, Hazel
    University of Manchester, England .
    Short, Andrea
    University of Manchester, England .
    Lobell, Anna
    Uppsala University, Sweden .
    Kampe, Olle
    Uppsala University, Sweden .
    Bensing, Sophie
    Uppsala University, Sweden Karolinska Institute, Sweden .
    Betterle, Corrado
    University of Padua, Italy .
    Kasperlik-Zaluska, Anna
    Medical Centre Postgrad Educ, Poland .
    Zurawek, Magdalena
    Polish Academic Science, Poland .
    Fichna, Marta
    Polish Academic Science, Poland .
    Kockum, Ingrid
    Karolinska Institute, Sweden Karolinska Institute, Sweden .
    Nordling Eriksson, Gabriel
    Karolinska Institute, Sweden .
    Ekwall, Olov
    University of Gothenburg, Sweden .
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Dahlqvist, Per
    Umeå University, Sweden .
    Hulting, Anna-Lena
    Karolinska Institute, Sweden .
    Penna-Martinez, Marissa
    Goethe University of Frankfurt, Germany .
    Meyer, Gesine
    Goethe University of Frankfurt, Germany .
    Kahles, Heinrich
    Goethe University of Frankfurt, Germany .
    Badenhoop, Klaus
    Goethe University of Frankfurt, Germany .
    Hahner, Stephanie
    University Hospital Wuerzburg, Germany .
    Quinkler, Marcus
    Charite, Germany .
    Falorni, Alberto
    University of Perugia, Italy .
    Phipps-Green, Amanda
    University of Otago, New Zealand .
    Merriman, Tony R.
    University of Otago, New Zealand .
    Ollier, William
    University of Manchester, England .
    Cordell, Heather J.
    Newcastle University, England .
    Undlien, Dag
    Oslo University Hospital, Norway University of Oslo, Norway .
    Czarnocka, Barbara
    Medical Centre Postgrad Educ, Poland .
    Husebye, Eystein
    University of Bergen, Norway Haukeland Hospital, Norway .
    Pearce, Simon H. S.
    Newcastle University, England .
    Association of Autoimmune Addisons Disease with Alleles of STAT4 and GATA3 in European Cohorts2014Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 3, s. 0088991-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Gene variants known to contribute to Autoimmune Addisons disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

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  • 45.
    Nilsson, A. G.
    et al.
    University of Gothenburg, Sweden.
    Marelli, C.
    ViroPharma SPRL, England.
    Fitts, D.
    ViroPharma Inc, Sweden.
    Bergthorsdottir, R.
    University of Gothenburg, Sweden.
    Burman, P.
    Skånes University Hospital, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Eden Engstrom, B.
    University of Uppsala Hospital, Sweden.
    Olsson, T.
    Umeå University, Sweden.
    Ragnarsson, O.
    University of Gothenburg, Sweden.
    Ryberg, M.
    Umeå University, Sweden.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Lennernas, H.
    Uppsala University, Sweden.
    Skrtic, S.
    University of Gothenburg, Sweden; AstraZeneca RandD, Sweden.
    Johannsson, G.
    University of Gothenburg, Sweden.
    Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency2014Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 171, nr 3, s. 369-377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Design: Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods: Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results: In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

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  • 46.
    Nilsson, Anna G.
    et al.
    University of Gothenburg, Sweden.
    Bergthorsdottir, Ragnhildur
    University of Gothenburg, Sweden.
    Burman, Pia
    Lund University, Sweden.
    Dahlqvist, Per
    Umeå University, Sweden.
    Ekman, Bertil
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Eden Engstrom, Britt
    University Hospital, Sweden.
    Ragnarsson, Oskar
    University of Gothenburg, Sweden.
    Skrtic, Stanko
    University of Gothenburg, Sweden; AstraZeneca RandD, Sweden.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Achenbach, Heinrich
    Shire Int GmbH, Switzerland.
    Uddin, Sharif
    Shire, MA USA.
    Marelli, Claudio
    Shire Int GmbH, Switzerland.
    Johannsson, Gudmundur
    University of Gothenburg, Sweden.
    Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study2017Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 176, nr 6, s. 715-725Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P amp;lt; 0.0001) and HDL cholesterol (0.2 mmol/L; P amp;lt; 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

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  • 47.
    Nowak, Christoph
    et al.
    Karolinska Inst, Sweden; Diamyd Med AB, Sweden.
    Lind, Marcus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
    Sumnik, Zdenek
    Charles Univ Prague, Czech Republic; Motol Univ Hosp, Czech Republic.
    Pelikanova, Terezie
    Inst Clin & Expt Med, Czech Republic.
    Chavez, Lia Nattero
    Hosp Univ Ramon y Cajal, Spain.
    Lundberg, Elena
    Umeå Univ, Sweden.
    Rica, Itxaso
    Cruces Univ Hosp, Spain.
    Martinez-Brocca, Maria A.
    Virgen Macarena Univ Hosp, Spain.
    Ruiz de Adana, Mari Sol
    Gen Univ Hosp, Spain.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. Orebro Univ, Sweden.
    Hanas, Ragnar
    NU Hosp Grp, Sweden.
    Hernandez, Cristina
    Vall dHebron Hosp, Spain.
    Clemente-Leon, Maria
    Vall dHebron Hosp, Spain.
    Gomez-Gila, Ana
    Virgen Rocio Univ Hosp, Spain.
    Ferrer Lozano, Marta
    Miguel Servet Univ Hosp, Spain.
    Sas, Theo
    Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    Pruhova, Stepanka
    Charles Univ Prague, Czech Republic; Motol Univ Hosp, Czech Republic.
    Dietrich, Fabricia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Puente Marin, Sara
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Hannelius, Ulf
    Diamyd Med AB, Sweden.
    Casas, Rosaura
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Intralymphatic GAD-Alum (Diamyd (R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ22022Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, nr 9, s. 2644-2651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). Methods DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide &gt; 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 mu g GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. Results We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time &gt; 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. Conclusions Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.

  • 48.
    Onnestam, Lisa
    et al.
    University of Gothenburg, Sweden .
    Berinder, Katarina
    Karolinska University Hospital Solna, Sweden .
    Burman, Pia
    Skåne University Hospital, Sweden .
    Dahlqvist, Per
    Umeå University, Sweden .
    Eden Engstrom, Britt
    University of Uppsala Hospital, Sweden .
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Filipsson Nystrom, Helena
    University of Gothenburg, Sweden .
    National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden2013Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, nr 2, s. 626-635Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence. less thanbrgreater than less thanbrgreater thanObjective: The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas. less thanbrgreater than less thanbrgreater thanDesign: This was an observational study. less thanbrgreater than less thanbrgreater thanSetting: The study was conducted at tertiary referral centers. less thanbrgreater than less thanbrgreater thanPatients: The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients medical records were studied until the latest follow-up [median 5.0 years (range andlt; 1-20 years)]. less thanbrgreater than less thanbrgreater thanMain Outcome Measurements: Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured. less thanbrgreater than less thanbrgreater thanResults: The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs andlt; 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022). less thanbrgreater than less thanbrgreater thanConclusion: This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas. (J Clin Endocrinol Metab 98: 626-635, 2013)

  • 49.
    Papadopoulou-Marketou, Nektaria
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. University of Athens, Greece.
    Margeli, Alexandra
    Aghia Sophia Childrens Hospital, Greece.
    Papassotiriou, Ioannis
    Aghia Sophia Childrens Hospital, Greece.
    Chrousos, George P.
    University of Athens, Greece.
    Kanaka-Gantenbein, Christina
    University of Athens, Greece.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    NGAL as an Early Predictive Marker of Diabetic Nephropathy in Children and Young Adults with Type 1 Diabetes Mellitus2017Ingår i: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, artikel-id 7526919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims. Type 1 diabetes (T1D) is often associated with early microvascular complications. Previous studies demonstrated that increased systolic (SAP) and diastolic arterial blood pressures (DAP) are linked to microvascular morbidity in T1D. The aim of the study was to investigate the predictive role of neutrophil gelatinase-associated lipocalin (NGAL) in unravelling early cardiorenal dysfunction in T1D. Methods. Two T1D patient groups participating in two-centre prospective cohorts were studied. Group A consisted of 57 participants aged 13.9 years (SD: 3.1) and group B consisted of 59 patients aged 28.0 years (SD: 4.4). Forty-nine healthy children [age: 10.5 years (SD: 6.6)] and 18 healthy adults [age 27.7 years (SD: 4.2)] served as controls. Serum concentrations of NGAL (ELISA) were determined, and SAP and DAP were examined (SAP and DAP also expressed as z-scores in the younger group). Results. NGAL correlated positively with SAP in both patient groups (P = 0 020 and P = 0 031, resp.) and SAP z-score (P = 0 009) (group A) and negatively with eGFR in both groups (P amp;lt; 0 001 and P amp;lt; 0 001, resp.). Conclusions. NGAL may be proposed as a biomarker of early renal dysfunction even in nonalbuminuric T1D patients, since it was strongly associated with renal function decline and increasing systolic arterial pressure even at prehypertensive range in people with T1D, in a broad age range.

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  • 50.
    Papadopoulou-Marketou, Nektaria
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken. University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children’s Hospital, Athens, Greece.
    Whiss, Per A
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten.
    Eriksson, Andreas C
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten.
    Hyllienmark, Lars
    Clinical Neurophysiology, Karolinska University Hospital, Stockholm, Sweden.
    Papassotiriou, Ioannis
    Department of Clinical Biochemistry, Aghia Sophia Children’s Hospital, Athens, Greece.
    Wahlberg, Jeanette
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Endokrinmedicinska kliniken.
    Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy2021Ingår i: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 18, nr 2, artikel-id 14791641211002470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.

    METHODS: Thirty-three type 1 diabetes patients, aged 20-35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques.

    RESULTS: TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = -0.49 and r = -0.51, respectively), foot neuropathy impairment assessment score (NIA; r = -0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = -0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively).

    CONCLUSIONS: This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.

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