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  • 1.
    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, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Health-Related Quality of Life In Patients With Adrenal Insufficiency Receiving Plenadren Compared With Immediate-Release Hydrocortisone.2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 7, p. A616-Article in journal (Refereed)
    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.

  • 2.
    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, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Erfurth, E M.
    Skånes University Hospital Malmö Lund, Sweden .
    Svensson, J
    University of Gothenburg, Sweden .
    Wahlberg, J
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    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 Mortality2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 4, p. 1466-1475Article in journal (Refereed)
    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)

  • 3.
    Burman, Pia
    et al.
    Lund University, Sweden.
    Eden-Engstrom, Britt
    Uppsala University, Sweden.
    Ekman, Bertil
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Anders Karlsson, F.
    Uppsala University, Sweden.
    Schwarcz, Erik
    University of Örebro, Sweden.
    Wahlberg Topp, Jeanette
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Limited value of cabergoline in Cushings disease: a prospective study of a 6-week treatment in 20 patients2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, no 1, p. 17-24Article in journal (Refereed)
    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 >= 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 >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >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.

  • 4.
    Dahlqvist, Per
    et al.
    Norrlands Universitetssjukhus, Umeå .
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna .
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg .
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    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].2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2226-2227Article in journal (Other academic)
  • 5.
    Dahlqvist, Per
    et al.
    Norrlands ­universitetssjukhus, Umeå.
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna.
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska universitetssjukhuset, Göteborg.
    Hulting, Anna-Lena
    Karolinska universitetssjukhuset, Solna.
    Nationellt kort vid binjurebarkssvikt: Nytt varningskort kan leda till bättre handläggning och ökad patientsäkerhet2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2226-2227Article in journal (Refereed)
    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.

  • 6.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Alstrand, N
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. County Hospital, Kalmar .
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life2014In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 46, no 1, p. 48-53Article in journal (Refereed)
    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.

  • 7.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Blomgren, Johan
    Internal Medicine County Hospital, Eksjö.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    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 insufficiency2012In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 1, p. 18-25Article in journal (Refereed)
    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.

  • 8.
    Ekman, Bertil
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Wahlberg Topp, Jeanette
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Urine oligosaccharide pattern in patients with hyperprolactinaemia2015In: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 32, no 8, p. 635-641Article in journal (Refereed)
    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.

  • 9.
    Gullstrand, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Ilonen, Jorma
    Dept of Microbiology Kuopio, Finland.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study2008In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, no 3 PART 1, p. 182-190Article in journal (Refereed)
    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.

  • 10.
    Holmberg, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Wahlberg (Topp), Jeanette
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population2007In: British Journal of Nutrition, ISSN 0007-1145, Vol. 97, no 1, p. 111-116Article in journal (Refereed)
    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.

  • 11.
    Hyllienmark, Lars
    et al.
    Karolinska Institute, Sweden .
    Alstrand, Nils
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Jonsson, Bjorn
    Uppsala University, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Cooray, Gerald
    Karolinska Institute, Sweden .
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 10, p. 3187-3194Article in journal (Refereed)
    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.

  • 12.
    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
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dahlqvist, P
    Umea University Hospital.
    Ryberg, M
    Umea University Hospital.
    Ragnarsson, O
    Sahlgrens University Hospital.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    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, pp2010In: ENDOCRINE REVIEWS, Endocrine Society , 2010, Vol. 31, no 3Conference paper (Refereed)
    Abstract [en]

    n/a

  • 13.
    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
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Engström, B. E
    Uppsala University.
    Olsson, T.
    Umeå University.
    Ragnarsson, O.
    Sahlgrenska Academy, University of Gothenburg.
    Ryberg, M.
    Umeå University.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    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 formulation2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 2, p. 473-481Article in journal (Refereed)
    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.

  • 14.
    Landberg, Eva
    et al.
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    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
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, no 1-2, p. 220-225Article in journal (Refereed)
    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.

  • 15.
    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, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    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 12016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 20104Article in journal (Refereed)
    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.

  • 16.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old2002In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, p. 289-292Article in journal (Refereed)
    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.

  • 17.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    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 Cohorts2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, p. 0088991-Article in journal (Refereed)
    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.

  • 18.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    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 insufficiency2014In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 171, no 3, p. 369-377Article in journal (Refereed)
    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.

  • 19.
    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
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Filipsson Nystrom, Helena
    University of Gothenburg, Sweden .
    National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 2, p. 626-635Article in journal (Refereed)
    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)

  • 20.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Psychological stress may induce diabetes-related autoimmunity in infancy2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 2, p. 290-295Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.

    RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.

    RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.

    CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.

  • 21.
    Svanberg, Christina
    et al.
    Region Östergötland, Public Dental Health Care. County Council Jamtland, Sweden.
    Norevall, Lars-Inge
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ekman, Bertil
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Wahlberg Topp, Jeanette
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Bågesund, Mats
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care.
    Cephalometric analysis of adults with Turner syndrome2016In: Swedish Dental Journal, ISSN 0347-9994, Vol. 40, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    Turner syndrome (TS) is a genetic disorder of females with a prevalence of 1/2000-3000 live female births. The aim of this study was to compare cephalometric variables from adult women diagnosed with TS to a standardized reference group of 31-year old healthy women, and to evaluate the possible effects of human growth hormone (hGH) therapy in women with TS. Registered TS subjects in the Southeast region of Sweden were invited to take part in the study. Twenty-one women aged 36 +/- 13(18-57) years accepted participation. Lateral radiographs of the head were analyzed using standard cephalometric methods (Hasund analysis) and with the commercially available soft-ware program FACAD. Comparisons were made with roentgen-cephalometric standards from a reference group of nineteen 31-year old Swedish women. Analysis of the cephalometric radiographs from the TS subjects showed a more retrognathic maxilla (SNA 80.3 +/- 5.4) (p=0.0460) and mandible (SNB 77.0 +/- 5.2) (p=0.0014), and a correspondingly backward position of the chin (SN/Pg 78.9 +/- 5.5) (p=0.0046) as compared to the reference values of 31-year old women (SNA 83.2 +/- 3.0, SNB 81.5 +/- 2.3 and SNPg 83.0 +/- 2.3, respectively). In addition there was an increased posterior inclination of the maxilla (SN/NL 8.6 +/- 4.1), as compared to the reference values (SN/NL 5,3 +/- 2.7) (p=0.0048). There were no significant differences regarding sagittal or vertical jaw relations, mandibular inclination or cranial base angle between the TS-group and the 31-year olds with the reference values. No significant difference was seen in jaw relationship, as measured by the ANB value, however the Wits(index) (3.3 +/- 3.5) was higher (p=0.0001) than the reference values (-0.1 +/- 1.8). Subjects with or without previous hGH administration did not show any significant differences in cephalometric values. In conclusion, women with TS had a significantly more retrognathic maxilla (SNA) and mandible (SNB) and a correspondingly significantly posterior position of the chin (SN/Pg), a significantly increased posterior inclination of the maxilla (SN/NL) and a significantly increased Witsindex as compared to the reference group of 31-year old women. No craniofacial variables differed significantly between previously hGH-treated and not hGH-treated women with TS.

  • 22.
    Wahlberg, Jeanette
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Environmental determinants associated with Type 1 diabetes-related autoantibodies in children2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Type 1 diabetes is a severe disease, which affects children with potentially severe consequences. The global incidence of Type 1 diabetes is increasing rapidly especially in young children. Second to Finland, Sweden has the highest incidence of Type 1 diabetes in the world.

    The rapidly increasing incidence cannot be explained by a possible variability of the presence of risk genes in the population, but rather environmental factors.

    Therefore, environmental factors contributing to ß-cell auto immunity should be of importance for the process leading up to clinical Type I diabetes in genetically predisposed individuals. Those factors should preferably be revealed early in life. The aim of this thesis was to investigate a large population of Swedish children in order to identify environmental factors, which could contribute to the autoimmune reaction towards insulin-producing ß-cells.

    Material and methods

    Families from the prospective population-based ABIS-project (All Babies in southeast Sweden) were studied. Blood samples from children were analysed at birth, one year and 2½ years of age for diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2A) and Glutamic Acid Decarboxylase (GAD). The parents completed questionnaires at birth, one year and 2½ years of age.

    Results

    Short breast-feeding period, early exposure to cow's milk formula and late introduction of gluten-containing foods as well as large consumption of cow's milk at the age of one year were all risk determinants for development of autoantibodies at 2½ years of age. Combined early introduction of cow's milk formula and late introduction of gluten-containing food increased the risk six times for acquiring persistent autoantibodies at 2½ years of age. Parenting stress and experiences of serious life events were associated with the induction of diabetes-related autoimmunity. Infections during pregnancy are related to diabetes-related autoantibodies in cord blood and at the age of one year.

    Allergic symptoms such as rash, wheezing, allergy against fur-bearing animals and food allergies implied a risk for development of diabetes-related autoantibodies. Autoantibodies in cord blood had disappeared at the age of one year, and can therefore not be used as a screening method to predict diabetes in the general population.

    Conclusions

    None of the examined risk factors alone can explain Type 1 diabetes-related autoimmunity; but early nutrition, parental stress and infections can contribute to the development of diabetes-related autoantibodies.

    Autoantibodies in cord blood cannot be used to predict later diabetes-related autoimmunity. Different aberrances in the immune system seem to co-exist in certain individuals.

    List of papers
    1. Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old
    Open this publication in new window or tab >>Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old
    2002 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, p. 289-292Article in journal (Refereed) Published
    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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26537 (URN)10.1111/j.1749-6632.2002.tb02989.x (DOI)11098 (Local ID)11098 (Archive number)11098 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Psychological stress may induce diabetes-related autoimmunity in infancy
    Open this publication in new window or tab >>Psychological stress may induce diabetes-related autoimmunity in infancy
    Show others...
    2005 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 2, p. 290-295Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.

    RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.

    RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.

    CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13631 (URN)10.2337/diacare.28.2.290 (DOI)
    Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2017-12-13Bibliographically approved
    3. Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children
    Open this publication in new window or tab >>Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children
    Show others...
    2005 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 6, no 4, p. 199-205Article in journal (Refereed) Published
    Abstract [en]

    We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2005
    Keywords
    Autoantibodies, cow’s milk, gastrointestinal infections, seasonality, T1D
    National Category
    Immunology
    Identifiers
    urn:nbn:se:liu:diva-12437 (URN)10.1111/j.1399-543X.2005.00129.x (DOI)
    Available from: 2008-09-04 Created: 2008-09-04 Last updated: 2017-12-05Bibliographically approved
    4. Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 2½-year-old Swedish children
    Open this publication in new window or tab >>Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 2½-year-old Swedish children
    2006 (English)In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 95, no 3, p. 603-608Article in journal (Refereed) Published
    Abstract [en]

    We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2½ years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2½-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (≤2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of 1 year (odds ratio 2·6) represented a risk for GADA, and maternal coeliac disease (odds ratio 2·9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6·0 for positivity for at least one autoantibody at 1 and 2½ years of age. The induction of autoantibodies by the age of 2½ years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of β-cell autoantibodies in 2½-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of 1 year.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-34825 (URN)10.1079/BJN20051676 (DOI)23452 (Local ID)23452 (Archive number)23452 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    5. Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children
    Open this publication in new window or tab >>Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children
    2011 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, no 7, p. 604-610Article in journal (Refereed) Published
    Abstract [en]

    A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1–3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9–29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing, 2011
    Keywords
    asthma; allergy; GADA; IA-2A; T1D
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-76272 (URN)10.1111/j.1399-5448.2011.00758.x (DOI)000296345600003 ()1466648 (PubMedID)
    Available from: 2012-04-01 Created: 2012-04-01 Last updated: 2017-12-07Bibliographically approved
  • 23.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Atypical or typical adrenocorticotropic hormone-producing pulmonary carcinoids and the usefulness of 11C-5-hydroxytryptophan positron emission tomography: two case reports2013In: Journal of Medical Case Reports, ISSN 1752-1947, E-ISSN 1752-1947, Vol. 7, p. 80-Article in journal (Refereed)
    Abstract [en]

    Introduction

    Pulmonary carcinoids associated with ectopic adrenocorticotropic hormone secretion have a good prognosis if histological examination shows typical pulmonary carcinoid and low proliferation, whereas a poor outcome is linked to atypical pulmonary carcinoid and high proliferation. Here we describe the diagnostic challenges to find the tumor in Cushing’s syndrome secondary to ectopic adrenocorticotropic hormone secretion in two cases with an atypical and a typical pulmonary carcinoid, respectively.     

    Case presentation

    A 63-year-old Caucasian woman presented with aggressive clinical features related to Cushing’s syndrome, having very high levels of urinary cortisol and circulating adrenocorticotropic hormone and cortisol. Magnetic resonance imaging showed no pituitary tumor, and bilateral inferior petrosal sinus sampling revealed no central peripheral ratio of adrenocorticotropic hormone. Computed tomography and 111Indium-pentetreoide somatostatin receptor scintigraphy could not visualize any ectopic tumor. The patient was referred for an 11C-5-hydroxytryptophan positron emission tomography, and a small 8mm nodule in her left lung was found. The tumor was removed via a lateral thoracic incision and wedge excision. The histological examination showed an atypical carcinoid with Ki-67 index of 9 to 10%, and an additional lobectomy was performed.     

    The second patient, a 22-year-old Caucasian man, also presented with aggressive Cushing’s syndrome, with very high urinary cortisol levels and increased circulating cortisol as well as adrenocorticotropic hormone levels. A magnetic resonance imaging scan of the pituitary showed no tumor, whereas a 12×9×14mm tumor was detected in the right lung on the primary computed tomography scan and no further investigation was performed. The tumor was removed via a lateral thoracic incision and wedge excision. A typical carcinoid with Ki-67 index of 1 to 2% was found and no further surgery was performed.     

    After surgical removal, the biochemical disturbances resolved and significant clinical improvement were achieved in both patients after 24 months of follow up.     

    Conclusions

    Diagnostic evaluation time is limited due to the aggressive course in ectopic adrenocorticotropic hormone-dependent Cushing’s syndrome. We suggest that 11C-5-hydroxytryptophan positron emission tomography could be considered early as a secondary diagnostic tool when primary computed tomography and/or magnetic resonance imaging scans fail to show any tumor.

  • 24.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fredriksson, Jenny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn. Linköping University, Faculty of Health Sciences.
    Vaccinations may induce diabetes-related autoantibodies in one-year-old children2003In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1005, p. 404-408Article in journal (Refereed)
    Abstract [en]

    Vaccinations have been discussed as one among many environmental candidates contributing to the immune process that later may lead to type 1 diabetes. ABIS (All Babies in Southeast Sweden) is a prospective cohort study following a nonselected birth cohort of general population. In a randomly selected sample collection from 4400 children, GADA and IA-2A have been determined at the age of 1 year. The information on vaccinations was collected from questionnaires answered by the parents and was related to β cell autoantibodies. When studying the induction of autoantibodies using the autoantibody level of 90th percentile as cutoff level, hemophdus influenza B (HIB) vaccination appeared to be a risk factor for IA-2A [OR 5.9 (CI 1.4-24.4; p = 0.01)] and for GADA [OR 3.4 (CI 1.1-10.8; p = 0.04)] in logistic regression analyses. Furthermore, the titers of IA-2A were significantly higher (p < 0.01 in Mann-Whitney test) in those children who had got HIB vaccination. When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes, BCG vaccination was associated with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A. This might be of importance under circumstances when the β cell-related immune response is activated by other mechanisms.

  • 25.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fredriksson (Walldén), Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nikolic, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children2005In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 6, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

    We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.

  • 26.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ledin, Torbjön
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Bågesund, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care, Centre for Orthodontics and Paediatric Dentistry.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Impaired Postural Balance in Turner Syndrom2013In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 45, no 7, p. 537-540Article in journal (Refereed)
    Abstract [en]

    An impaired body balance has been found in Turner syndrome (TS) in clinical tests like Rombergs’s test and walking on a balance beam. The aim of the study was to assess postural balance in TS subjects with specific balance testing using dynamic posturography and relate to body composition. Nineteen TS subjects (20–57 years) were included. Balance was measured with dynamic posturography (Equitest) and compared with 19 sex and age-matched controls (22–59 years). Equitest, visual, vestibular, and somatosensory systems were provoked with increasing difficulty (6 tests, SO1–SO6) and body sway was measured with a dual forceplate. Body composition was measured with DXA. No difference was found between the TS subjects and the controls on fixed platform with open eyes (SO1), with closed eyes (SO2), with stable platform and visual disorientation (SO3), or on unstable platform with open eyes (SO4). In the difficult tests on unstable platform the TS subjects did worse compared with controls both in the test with eyes closed (SO5), p<0.01, and in the test with visual disorientation (SO6), p<0.05. Composite (a merge of all six recordings) was significantly lower in the TS-group, p<0.05. In the TS group high total body weight was related to worse outcome on tests SO5, SO6, and composite, while total bone mass, age, height, or waist showed no significant association with balance scores. Our findings indicate that TS could have an increased risk for falling due to impaired ability to manage complex coordination tasks.

  • 27.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 2½-year-old Swedish children2006In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 95, no 3, p. 603-608Article in journal (Refereed)
    Abstract [en]

    We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2½ years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2½-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (≤2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of 1 year (odds ratio 2·6) represented a risk for GADA, and maternal coeliac disease (odds ratio 2·9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6·0 for positivity for at least one autoantibody at 1 and 2½ years of age. The induction of autoantibodies by the age of 2½ years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of β-cell autoantibodies in 2½-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of 1 year.

  • 28.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Waarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children2011In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, no 7, p. 604-610Article in journal (Refereed)
    Abstract [en]

    A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1–3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9–29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life.

  • 29.
    Wahlberg Topp, Jeanette
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Ekman, Bertil
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Nystrom, Lennarth
    Umeå University, Sweden.
    Hanson, Ulf
    Uppsala University, Sweden.
    Persson, Bengt
    Karolinska Institute, Sweden.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Gestational diabetes: Glycaemic predictors for fetal macrosomia and maternal risk of future diabetes2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 114, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate how glucose levels at diagnosis of gestational diabetes (GDM) are associated with infant birth weight and long-term risk of manifest diabetes mellitus in the mother. Methods: In a case control study GDM pregnancies (n = 2085) were compared with non-GDM pregnancies matched for day of delivery and obstetric unit (n = 3792). GDM was defined as capillary blood glucose (cB-glucose) &gt;9.0 mmol/l (plasma glucose &gt;10.0 mmol/l) after a 75 g oral glucose tolerance test (OGTT). The GDM cohort were followed up 8.5-13.5 yrs after initial diagnosis with a questionnaire, answered by 1324 GDM women (65%). Results: GDM women had higher mean infant birth-weight compared with controls (3682 g vs. 3541 g, P &lt; 0.001). In multiple linear regression analysis, birth weight was positively correlated to fasting cB-glucose at GDM diagnosis (P &lt; 0.001), increased week of gestation (P &lt; 0.001) and BMI before pregnancy (P &lt; 0.003), while 2 h OGTT cB-glucose values &gt;= 9.0 mmol/l were not related. Infants born to mothers with fasting cB-glucose &gt;= 4.5 mmol/l had no increased mean birth-weight or macrosomia (&gt;= 4500 g) compared to controls. In the follow up 334/1324 women (25%) of the GDM women had developed diabetes, 215 type 2 diabetes, 46 type 1 diabetes and 72 unclassified diabetes. In logistic regression fasting cB-glucose and 2 h OGTT cB-glucose at diagnosis of GDM as well as BMI &gt;25 and origin outside Europe were risk factors for manifest diabetes. Conclusions: Fasting blood glucose at diagnosis of GDM gives important information besides 2 h OGTT glucose about pregnancy outcome and future risk for maternal diabetes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 30.
    Wahlberg Topp, Jeanette
    et al.
    Department of Medical Cell Biology, Uppsala University, Sweden.
    Korsgren, Olle
    Department of Medical Cell Biology, Uppsala University, Sweden..
    Welsh, Nils
    Department of Medical Cell Biology, Uppsala University, Sweden..
    Jansson, Leif
    Department of Medical Cell Biology, Uppsala University, Sweden..
    Evidence of a negative feedback system regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants.1998In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 66, no 10, p. 1392-1394Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the present study was to investigate the long-term regulation of pancreatic beta-cell volume after pancreas transplantation into adult rats.

    METHODS: A syngeneic pancreaticoduodenal transplantation was made in normoglycemic Wistar-Furth rats. By this means, the recipients doubled their pancreatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insulin from both the native and transplanted pancreata, and in the native pancreas of age-matched Wistar-Furth rats that did not receive transplants.

    RESULTS: No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and transplanted pancreas when compared with that of age-matched controls. However, the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pancreas in control animals. No signs of increased apoptosis in any of the glands could be seen during the first postoperative week or after 9 months.

    CONCLUSIONS: These findings provide evidence of a negative feedback system, which regulates the total beta-cell volume to the levels seen in age-matched rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished replicatory rate of the beta-cells.

  • 31.
    Wahlberg Topp, Jeanette
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Tillmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekman, Bertil
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Effects of prolactin on platelet activation and blood clotting2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 221-228Article in journal (Refereed)
    Abstract [en]

    Increased levels of prolactin often coincide with an increased risk for thromboembolic events, but it is unclear whether a direct causal relation exists. Our aim was to examine the effect of prolactin on platelet function. In addition to using recombinant prolactin for experiments in vitro, we analyzed platelet function by flow cytometry in a group of 13 females with hyperprolactinaemia and 18 healthy female controls. Platelet activation was measured by P-selectin expression and by the amount of platelet-bound fibrinogen after stimulation with adenosine diphosphate (ADP), collagen-related peptide and the protease activated receptor (thrombin receptor) (PAR)-activating peptides PAR4-AP and PAR1-AP. Free oscillation rheometry was used to measure clotting time in whole blood. No significant effect on platelet activation or clotting time could be seen in in vitro experiments by adding recombinant prolactin. However, significantly lower P-selectin expression was found in the hyperprolactinemic group when platelets were activated by ADP (5 and 10 mu M) or PAR4-AP. The expression of fibrinogen did not differ between the two groups for any of the activators used. For all samples, inverse significant correlations between P-selectin expression and prolactin concentration were found for both 5 mu M ADP (r = 0.61, p andlt; 0.01), 10 mu M ADP (r = -0.62, p andlt; 0.001) and PAR4-AP (r = -0.69, p andlt; 0.001). Thrombin cleavage of recombinant prolactin resulting in a 16 kDa C-terminal fragment did not alter the P-selectin expression upon activation. We found an indirect inhibitory effect of prolactin on platelets in hyperprolactinemic patients, suggesting that prolactin might have a protective role in thromboembolic disease.

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