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  • 1.
    Acerini, Carlo L.
    et al.
    University of Cambridge, England.
    Wac, Katarzyna
    University of Geneva, Switzerland.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lehwalder, Dagmar
    Merck KGaA, Germany.
    Optimizing Patient Management and Adherence for children receiving Growth Hormone2017In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 8, article id 313Article in journal (Refereed)
    Abstract [en]

    Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

  • 2.
    Kvernebo-Sunnergren, Kjersti
    et al.
    Ryhov Cty Hosp, Sweden; Univ Gothenburg, Sweden.
    Ankarberg-Lindgren, Carina
    Univ Gothenburg, Sweden.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Andersson, Mats X.
    Univ Gothenburg, Sweden.
    Samuelsson, Lena
    Sahlgrens Univ Hosp, Sweden.
    Lovmar, Lovisa
    Sahlgrens Univ Hosp, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sweden.
    Hyperestrogenism Affects Adult Height Outcome in Growth Hormone Treated Boys With Silver-Russell Syndrome2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 780Article in journal (Refereed)
    Abstract [en]

    Background: Intrauterine growth retardation and short stature are common features in Silver-Russell syndrome (SRS). Despite recombinant growth hormone (rGH) treatment, poor pubertal height gain, affecting adult height (AH), is common. This study investigated whether growth patterns and estrogen concentrations are associated with AH outcome in rGH treated SRS males. Methods: In this retrospective longitudinal single-center study, 11 males with SRS were classified as non-responders (NR = 6) or responders (R = 5), depending on AH adjusted for midparental height. Epigenetic analysis and longitudinal growth measures, including bone age, rGH related parameters, pubertal development, gonadotropins and estrogen concentrations, were analyzed until AH. Results: Pubarche before 9 years was only observed in one NR. At 10 years of age, there was no difference in gonadotropins between NR and R. However, estradiol (E2) concentrations at 10 years of age showed a strong association to AH adjusted for MPH (r = -0.78, p amp;lt; 0.001). Serum E2 (pmol/L) was significantly higher in NR at ages 10 years [median (range) 2 (amp;lt;2-5) vs. amp;lt;2 (amp;lt;2)], 12 years [23 (10-57) vs. 2 (amp;lt;2-2)] and 14 years [77 (54-87) vs. 24 (amp;lt;2-38)] but not at 16 years. Birth weight standard deviation score (SDS) was lower in NR [-4.1 (-4.7 to -2.1) vs. -2.7 (-3.3 to -1.7)]. Weight gain (SDS) until pubertal onset was greater in NR [2.4 (1.4-3.5) vs. 0.8 (-0.4 to 1.7)] and pubertal height gain (SDS) was lower in NR [-1.0 (-2.7-0.4) vs. 0.1 (-0.1 to 1.1)]. At AH, a number of NR and R had high E2 concentrations and small testes. Conclusion: Increased E2 concentrations at age 10, 12, and 14 years were associated to less pubertal height gain, thus affecting AH. Due to the small number of patients, the results need to be confirmed in larger cohorts. The finding of impaired testicular development stresses the need of hormonal evaluation as a complement to clinical and radiological assessment when predicting AH in males with SRS.

  • 3.
    Lindenberger, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Reduced Venous Compliance in Young Women with Type 1 Diabetes - Further Aggravated by Prolonged Elevated Levels of HbA1c2016In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 7, no 126Article in journal (Refereed)
    Abstract [en]

    Background: Young patients with diabetes present with reduced compensatory responses to hypovolemic stress. Less compliant veins could be a contributing factor, since roughly two-thirds of the blood volume resides in the venous system as a blood reservoir, adjusting proper venous inflow to the heart. The aim of this study was to measure venous compliance and lower limb blood pooling during hypovolemic stress, and to correlate them to indices of diabetes severity and glucose control. Methods: Fifteen young women with type 1 diabetes (DW) and 18 healthy age-matched women (C) were subjected to lower body negative pressure (LBNP) (11-44 mmHg), creating hypovolemic stress. Lower limb blood pooling was measured with strain gage technique and venous compliance calculated as the relationship between Delta V/Delta P. Results: DW presented with reduced blood pooling (e.g., blood pooling during LBNP of 44 mmHg, DW, 1.69 +/- 0.10; C, 2.10 +/- 0.08 (ml/100 ml), and P = 0.003). Calculated venous compliance was also reduced in DW (e.g., compliance at 20 mmHg, DW, 0.046 +/- 0.003; C, 0.059 +/- 0.002 (ml/100 ml/mmHg), and P = 0.002). A progressive reduction in both venous compliance (P amp;lt; 0.007) and blood pooling (P amp;lt; 0.005) was seen with increasing level of HbA(1c), and furthermore, less strongly associated with presence of microvascular disease (signs of retinopathy). Conclusion: Women with type 1 diabetes present with both reduced venous compliance and blood pooling. The reductions were particularly present in patients with long-standing poor glycemic control.

  • 4.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala Univ, Sweden.
    Szakacs, Attila
    Univ Gothenburg, Sweden.
    Hallbook, Tove
    Univ Gothenburg, Sweden.
    Darin, Niklas
    Univ Gothenburg, Sweden.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Unexpected Fat Distribution in Adolescents With Narcolepsy2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 728Article in journal (Refereed)
    Abstract [en]

    Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

  • 5.
    Tababi, Mouna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Hypoxia Signaling and Circadian Disruption in and by Pheochromocytoma2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 612Article, review/survey (Refereed)
    Abstract [en]

    Disruption of the daily (i.e., circadian) rhythms of cell metabolism, proliferation and blood perfusion is a hallmark of many cancer types, perhaps most clearly exemplified by the rare but detrimental pheochromocytomas. These tumors arise from genetic disruption of genes critical for hypoxia signaling, such as von Hippel-Lindau and hypoxia-inducible factor-2 or cellular metabolism, such as succinate dehydrogenase, which in turn impacts on the cellular circadian clock function by interfering with the Bmal1 and/or Clock transcription factors. While pheochromocytomas are often nonmalignant, the resulting changes in cellular physiology are coupled to de-regulated production of catecholamines, which in turn disrupt circadian blood pressure variation and therefore circadian entrainment of other tissues. In this review we thoroughly discuss the molecular and physiological interplay between hypoxia signaling and the circadian clock in pheochromocytoma, and how this underlies endocrine disruption leading to loss of circadian blood pressure variation in the affected patients. We furthermore discuss potential avenues for targeting these tumor-specific pathophysiological mechanisms therapeutically in the future.

  • 6.
    Thorsell, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mathe, Aleksander A.
    Karolinska Institute, Sweden.
    Neuropeptide Y in Alcohol Addiction and Affective Disorders2017In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 8, article id 178Article, review/survey (Refereed)
    Abstract [en]

    Neuropeptide Y (NPY), a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS), as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptides regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor subtypes, may be attractive targets for treatment development for affective disorders, as well as for alcohol use disorders.

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