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Adriana J van Ballegooijen Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Marjolein Visser Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Marieke B Snijder Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Jacqueline M Dekker Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Giel Nijpels Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Coen D A Stehouwer Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Michaela Diamant Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Ingeborg A Brouwer Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Objective

A disturbed vitamin D–parathyroid hormone (PTH)–calcium axis may play a role in the pathogenesis of heart failure. Therefore, we investigated whether lower 25-hydroxyvitamin D (25(OH)D) and higher PTH are cross sectionally and after 8 years of follow-up associated with higher B-type natriuretic peptide (BNP) levels in older men and women.

Design and methods

We measured baseline 25(OH)D, PTH, and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was available in 2007–2009 in 278 subjects. Subjects were categorized according to season- and sex-specific quartiles of 25(OH)D and PTH at baseline. We studied the association of 25(OH)D and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Analyses were stratified by kidney function estimated glomerular filtration rate (eGFR; ≤60 ml/min per 1.73 m2) because of significant interaction.

Results

At baseline, subjects had a mean age of 69.9±6.6 years, mean 25(OH)D level was 52.2±19.5 nmol/l and mean PTH 6.1±2.4 pmol/l. Cross sectionally, 25(OH)D was associated with BNP in subjects with impaired kidney function (eGFR ≤60 ml/min) only. The association attenuated after adjustment for PTH. PTH was cross sectionally associated with BNP, also in subjects with impaired kidney function only: regression coefficient of highest quartile 9.9 pmol/l (95% confidence interval 2.5, 17.4) with a significant trend across quartiles. Neither 25(OH)D nor PTH was associated with BNP in longitudinal analyses.

Conclusion

This study showed overall no strong association between 25(OH)D and BNP. However, PTH was associated with BNP in subjects with impaired kidney function and may point to a potential role in myocardial function.

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L Johnsen Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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N B Lyckegaard Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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P Khanal Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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B Quistorff Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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K Raun Diabetes and Obesity Pharmacology, Novo Nordisk A/S, Måløv, Denmark

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M O Nielsen Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Objective

We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming.

Design

Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood).

Methods

Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE).

Results

In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.

Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.

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Paweł Komarnicki Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Paweł Gut Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Jan Musiałkiewicz Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Maja Cieślewicz Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Adam Maciejewski Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Prachi Patel Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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George Mastorakos Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Marek Ruchała Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland

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Introduction

Neuroendocrine tumors (NETs) are rare neoplasms that occur in various locations throughout the body. Despite their usually benign character, they might manifest with distant metastases. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) has previously been described as a useful biomarker in diagnosing carcinoid heart disease (CHD), a common advanced NETs manifestation. We observed plasma concentrations of NT-proBNP in metastatic midgut NETs over a 4-year period.

Objectives

We aimed to explore NT-proBNP concentrations in states of varying levels of cell proliferation and disease status. Our goal was to investigate NT-proBNP’s role in predicting disease progression in relation to previous research and up-to-date scientific guidelines.

Patients and methods

We performed a retrospective multivariate analysis of NT-proBNP concentrations in 41 midgut NETs patients treated with somatostatin analogs, all with liver metastases. NT-proBNP concentrations were measured in every patient across 16 evenly distanced time points over a 48-month period and were compared to variables such as sex, age, grading, Ki-67, primary tumor location, and CT findings.

Results

NT-proBNP concentrations correlated positively with higher liver tumor burden, higher grading, high Ki-67 levels, and with progressive disease in CT. There were no differences in NT-proBNP levels with regard to primary location (ileum vs jejunum), sex, and age.

Conclusion

We conclude that NT-proBNP is a useful analyte for monitoring NETs progression, due to its increased concentration in scenarios implying increased cellular proliferation. These long-term follow-up results align with previous findings and suggest an additional role for NT-proBNP in diagnostic algorithms, beyond a CHD biomarker.

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Eng-Loon Tng Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Yee Sian Tiong Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Aye Thida Aung Department of Medicine, Level 8, Tower A, Ng Teng Fong General Hospital, Singapore

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Nicole Ya Yuan Chong Department of Medicine, National University Hospital, Singapore

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Zhemin Wang Department of Medicine, National University Hospital, Singapore

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Background

Evidence on the efficacy and safety of anticoagulation in preventing stroke and thromboembolic events in people with thyrotoxic atrial fibrillation is scarce.

Objective

We evaluated the efficacy and safety of anticoagulation in people with thyrotoxic atrial fibrillation.

Methods

Our study protocol was published in the International Prospective Register of Systematic Reviews (registration no. CRD42020222782). Four databases and two systematic review registers were searched through 25 November 2020 for interventional and observational studies comparing anticoagulation therapy with active comparators, placebo, or no treatment in people with thyrotoxic atrial fibrillation. Random-effects meta-analysis and sensitivity analysis were performed. Quality of evidence was described using the GRADE framework.

Results

In the study, 23,145 records were retrieved. One randomized controlled trial and eight cohort studies were ultimately included. Effect estimates on the efficacy and safety of anticoagulation were extracted. Meta-analysis using the inverse variance and random-effects methods was conducted on four cohort studies with 3443 participants and 277 events. Anticoagulation in people with thyrotoxic atrial fibrillation reduced the risk of ischemic stroke and systemic thromboembolism by 3% (95% CI: 1–6%). Warfarin may prevent ischemic stroke in people with thyrotoxic atrial fibrillation if the CHA2DS2-VASc score exceeds 1 and when atrial fibrillation persists beyond 7 days. Direct oral anticoagulants may be associated with fewer bleeding events than warfarin.

Conclusions

Anticoagulation prevents ischemic stroke and systemic thromboembolism in people with thyrotoxic atrial fibrillation. Direct oral anticoagulants may be associated with fewer bleeding events.

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Robert A Hart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Robin C Dobos NSW Department of Primary Industries, Armidale, New South Wales, Australia

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Linda L Agnew Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Neil A Smart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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James R McFarlane Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12 ng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5 min after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.

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Kristin Viste Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Marianne A Grytaas Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Melissa D Jørstad Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Dag E Jøssang Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Eivind N Høyden Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Solveig S Fotland Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Dag K Jensen Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Kristian Løvås Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Hrafnkell Thordarson Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Bjørg Almås Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Gunnar Mellgren Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway

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Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedure may enhance the success rate. We invited 21 consecutive patients to participate in a study with intra-procedural point of care cortisol analysis. When this assay showed nonrepresentative sampling, new samples were drawn after redirection of the catheter. The study patients were compared using the 21 previous procedures. The intra-procedural cortisol assay increased the success rate from 10/21 patients in the historical cohort to 17/21 patients in the study group. In four of the 17 successful procedures, repeated samples needed to be drawn. Successful sampling at first attempt improved from the first seven to the last seven study patients. Point of care cortisol analysis during AVS improves success rate and reduces the need for reexaminations, in accordance with previous studies. Successful AVS is crucial when deciding which patients with PA will benefit from surgical treatment.

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Henri Honka Turku PET Centre, University of Turku, Turku, Finland

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Jukka Koffert Turku PET Centre, University of Turku, Turku, Finland
Department of Gastroenterology, Turku University Hospital, Turku, Finland

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Saila Kauhanen Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland

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Nobuyuki Kudomi Faculty of Medicine, Kagawa University, Kagawa, Japan

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Saija Hurme Department of Biostatistics, University of Turku, Turku, Finland

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Andrea Mari Institute of Neuroscience, National Research Council, Padua, Italy

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Andreas Lindqvist Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Nils Wierup Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Riitta Parkkola Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland

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Leif Groop Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Pirjo Nuutila Turku PET Centre, University of Turku, Turku, Finland
Department of Endocrinology, Turku University Hospital, Turku, Finland

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Aims/hypothesis

The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance.

Methods

A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls.

Results

Bariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test.

Conclusions/interpretation

Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.

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Milène Tetsi Nomigni INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Sophie Ouzounian INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Alice Benoit INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Jacqueline Vadrot INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Frédérique Tissier INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Sylvie Renouf INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Hervé Lefebvre INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Sophie Christin-Maitre INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Estelle Louiset INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France

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Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.

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P R van Dijk Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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S J J Logtenberg Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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K H Groenier Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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N Kleefstra Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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H J G Bilo Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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H J Arnqvist Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH–IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 μg/l (95% CI −0.94, 21.7 μg/l; P=0.06) and during s.c. insulin treatment was −2.2 μg/l (95% CI −13.5, 9.2 μg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 μg/l (95% CI −3.1, 28.5 μg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to −100.7 μg/l (95% CI −143.0, −58.3 μg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH–IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.

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Jung Soo Lim Department of Internal Medicine, Institute of Evidence-Based Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, South Korea

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Seung-Eun Lee Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea

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Jung Hee Kim Department of Internal Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, South Korea

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Jae Hyeon Kim Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea

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The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korean Endocrine Society
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Purpose

To evaluate the clinical characteristics and prognostic factors in patients with adrenocortical carcinoma (ACC) in South Korea.

Methods

A nationwide, registry-based survey was conducted to identify pathologically proven ACC at 25 tertiary care centers in South Korea between 2000 and 2014. Cox proportional hazard model and log-rank test were adopted for survival analysis.

Results

Two hundred four patients with ACC were identified, with a median follow-up duration of 20 months (IQR 5–52 months). The median age at diagnosis was 51.5 years (IQR 40–65.8 years), and ACC was prevalent in women (n = 110, 53.9%). Abdominal pain was the most common clinical symptom (n = 70, 40.2%), and ENSAT stage 2 was most common (n = 62, 30.4%) at the time of diagnosis. One hundred sixty-nine patients underwent operation, while 17 were treated with other modalities. The remission rate was 48%, and median recurrence-free survival time was 46 months. Estimated 5-year recurrence-free rate was 44.7%. There were more women, large tumor, atypical mitosis, venous invasion, and higher mitotic count in cancer recurrence group. Estimated 5-year overall survival and disease-specific survival rates were 64.5 and 70.6%, respectively. Higher ENSAT stage and advanced pathologic characteristics were risk factors for all-cause mortality of ACC. Large tumor size and cortisol-secreting tumor were additional risk factors for ACC-specific death.

Conclusions

We report the first epidemiologic study regarding ACC in an Asian population. ENSAT stage 4; lymph node involvement; non-operative group; and invasion of vein, sinusoid, or capsule were associated with an increased risk for all-cause mortality.

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