Clinical Endocrinology & Metabolism

Case Reports       Fifty Years After the First Description, MEN 2B Syndrome Diagnosis Is Still Late: Descriptions of Two Recent Cases     Rossella Elisei; Antonio Matrone; Laura Valerio; Eleonora Molinaro; Laura Agate ...   Despite the importance of an early diagnosis for the cure of thyroid cancer, diagnosis of MEN 2B is still difficult in nonreferral centers, thus threatening the definitive cure of patients.     Massive Ovarian Growth in a Woman With Severe Insulin-Resistant Polycystic Ovary Syndrome Receiving GnRH Analogue     Prapti Singh; Ariela Agress; Vanessa Kasarah Madrigal; Clara Magyar ; Nora Ostrzega ...   A woman with PCOS and hyperinsulinemia on a GnRH analogue demonstrated ovarian growth and folliculogenesis with confirmed granulosa cell proliferation by Ki-67. Insulin may be a granulosa cell mitogen.     Combined Pituitary Hormone Deficiency Caused by a Synonymous HESX1 Gene Mutation     Eduarda Coutinho; Carla Maria Brandão; Manuel Carlos Lemos   A novel synonymous HESX1 mutation affecting RNA splicing in a patient with combined pituitary hormone deficiency alerts to the need to carefully investigate all apparently silent genetic variants.       Meta-Analysis       Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies     Tiziana Feola; Alessia Cozzolino; Ilaria Simonelli ; Emilia Sbardella; Carlotta Pozza ...   Independently of disease control, pegvisomant used in monotherapy or combined with SSAs seems to improve glucose metabolism, reducing FPG, HbA1c, FPI, and HOMA-I.       Mini-Reviews       New Avenues in the Regulation of Gallbladder Motility—Implications for the Use of Glucagon-Like Peptide–Derived Drugs     Ida M Gether ; Christina Nexøe-Larsen; Filip K Knop   Recent studies have suggested that bile acids and GLP-2 terminate cholecystokinin-induced gallbladder contraction, and GLP-1 receptor agonist treatment decelerates gallbladder refilling.     Clinical and Pathological Aspects of Silent Pituitary Adenomas     Juliana Drummond; Federico Roncaroli; Ashley B Grossman ; Márta Korbonits   We present a concise review of the clinical and pathological aspects of silent pituitary adenomas in view of the new World Health Organization classification of pituitary adenomas.     Diagnosis and Management of Anabolic Androgenic Steroid Use     Bradley D Anawalt   AAS use suppresses gonadal function. Many AAS users return to normal gonadal function after discontinuation of AAS, but some might benefit from medical therapy.     Why Do Normal Children Have Acromegalic Levels of IGF-I During Puberty?     Anders Juul; Niels E Skakkebæk   We hypothesized that the acromegalic levels of GH and IGF-I seen in normal puberty are needed, not only for optimal final height, but also primarily to secure genital growth.     Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes     Rossana Calderon Moreno; Ana Navas-Acien; Esteban Escolar; David M Nathan ; Jonathan Newman ...   This review summarizes the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related cardiovascular disease, supported by the salutary effects of chelation in TACT.       Reports and Recommendations       Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee     Enrico Carmina; Ricardo Azziz; Wilma Bergfeld; Héctor F Escobar-Morreale; Walter Futterweit ...   The AE-PCOS Society appointed an expert task force to determine the current state of knowledge and provide evidence-based recommendations regarding female pattern hair loss.       Clinical Research Articles       Statin Treatment Decreases Mitochondrial Respiration But Muscle Coenzyme Q10 Levels Are Unaltered: The LIFESTAT Study     Tine Lovsø Dohlmann; Thomas Morville; Anja Birk Kuhlman ; Karoline Maise Chrøis; Jørn Wulff Helge ...   Mitochondrial respiratory capacity was assessed in skeletal muscle from statin-treated patients and complex II–linked respiration was reduced compared with that in well-matched control subjects.     Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1–Renal Axis in Man     Ali Asmar; Per K Cramon; Lene Simonsen; Meena Asmar ; Charlotte M Sorensen ...   The current study supports the existence of a GLP-1–mediated gut-renal axis for urinary sodium excretion in healthy participants as a mechanism contributing to extracellular volume regulation.     Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study     Sema Ciftci Dogansen; Ugur Cikrikcili; Gonca Oruk; Nilufer Ozdemir Kutbay ; Seher Tanrikulu ...   Dopamine agonist-induced impulse control disorder (ICD) in prolactinomas was assessed. Prevalence of ICD was 17%. ICD was more common in male patients with a history of smoking, alcohol use, or gambling.     Impact of USP8 Gene Mutations on Protein Deregulation in Cushing Disease     Isabel Weigand; Lisanne Knobloch; Jörg Flitsch; Wolfgang Saeger ; Camelia M Monoranu...   We provide a correlation between ubiquitin-specific peptidase 8 (USP8) mutations and the expression of key proteins in corticotroph tumors, suggesting these proteins to be USP8 substrates and potential treatment targets against Cushing disease.     Insulin Reduces Reaction of Follicular Granulosa Cells to FSH Stimulation in Women With Obesity-Related Infertility During IVF     Pei Xu; Bao-Yi Huang; Jia-Hui Zhan; Man-Ting Liu; Yang Fu ...   Obesity inhibits FSH receptor (FSHR) expression and estradiol production. Obese human chorionic gonadotropins and insulin resistance-modeled cells and compound 21 as an inhibitor of glycogen synthase kinase 3β could increase FSHR protein by the upregulation of β-catenin transcriptional activity.     High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease     George J Kahaly; Christian Wüster; Paul D Olivo; Tanja Diana   We demonstrate, for the first time, that dilution analysis of TSH receptor antibody levels markedly differentiates Graves thyroidal disease only vs Graves thyroidal and orbital disease.     Obstructive Sleep Apnea Is Associated With Altered Glycemic Patterns in Pregnant Women With Obesity     Sarah S Farabi; Linda A Barbour; Kristy Heiss; Nicole M Hirsch ; Emily Dunn ...   Obstructive sleep apnea, patterns of glycemia, and insulin action were measured in pregnant women with obesity. Obstructive sleep apnea was associated with 24-hour glycemia and insulin resistance.     Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients     Esben Thyssen Vestergaard; Astrid Johanneson Hjelholt; Rune E Kuhre; Niels Møller ; Pierre Larraufie ...   This study shows that acipimox treatment increases GLP-1 concentrations in healthy overweight and hypopituitary otherwise healthy subjects. GLP-1 and FFA levels correlated inversely.     Maternal BMI, Peripheral Deiodinase Activity, and Plasma Glucose: Relationships Between White Women in the HAPO Study     James E Haddow; Boyd E Metzger; Geralyn Lambert-Messerlian; Elizabeth Eklund ; Donald Coustan ...   Among euthyroid women, higher BMI is associated with higher T3 via peripheral conversion of T4 to T3 (deiodinase). T3 raises average glucose levels and probably contributes to GDM.     Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D     Petros Katsogiannos; Prasad G Kamble; Gretha J Boersma; F Anders Karlsson ; Per Lundkvist ...   A randomized study to explore the relationship between early changes in whole-body and adipose tissue metabolism showed no change in adipose insulin sensitivity despite reduction in adipocyte size.     11-Oxygenated C19 Steroids Do Not Decline With Age in Women     Aya T Nanba; Juilee Rege; Jianwei Ren; Richard J Auchus ; William E Rainey ...   This study of 100 pre- and 100 postmenopausal women shows that unlike other androgens, the adrenal 11-oxygenated C19 steroids do not decline with aging.     PDE5 Inhibition Stimulates Tie2-Expressing Monocytes and Angiopoietin-1 Restoring Angiogenic Homeostasis in Diabetes     Mary Anna Venneri; Federica Barbagallo; Daniela Fiore; Rita De Gaetano ; Elisa Giannetta ...   Tie2-expressing monocytes and Ang-1 are novel biomarkers linking chronic inflammation to vascular repair impairment in diabetes; their expression can be modulated by PDE5i.     Endoscopic Ultrasound-Guided Radiofrequency Ablation: A New Therapeutic Approach for Pancreatic Neuroendocrine Tumors     Kira Oleinikov; Alain Dancour; Julia Epshtein; Ariel Benson ; Haggi Mazeh ...   The initial experience with endoscopic ultrasound-guided radiofrequency ablation for functional and nonfunctional pancreatic neuroendocrine tumors was found to be a safe and feasible therapeutic modality in a selected cohort of patients with small tumors.     Resting Energy Expenditure and Metabolic Adaptation in Adolescents at 12 Months After Bariatric Surgery     Lisa Chu; Alissa Steinberg; Michael Mehta; Carley O’Kane ; Alene Toulany ...   REE was measured in adolescents who had undergone bariatric surgery. The REE was 25% lower at 12M after surgery, and a negative metabolic adaptation had occurred.     How To Identify Familial Premature Myocardial Infarction: Comparing Approaches To Identify Familial Hypercholesterolemia     Sabina Beheshti ; Christian M Madsen; Anette Varbo; Børge G Nordestgaard   FH criteria were applied for identification of familial premature myocardial infarction in individuals from the general population and identified a maximum of 13% of cases, leaving 87% undetected.     Metformin Triggers PYY Secretion in Human Gut Mucosa     Emily W Sun; Alyce M Martin; David A Wattchow; Dayan de Fontgalland ; Philippa Rabbitt...   We demonstrate that the first-line diabetes therapy metformin triggers the secretion of the anorectic gut hormone peptide YY from human ex vivo ileum and colon and the mechanism underlying this.     Association of Cardiovascular Autonomic Dysfunction With Peripheral Arterial Stiffness in Patients With Type 1 Diabetes     Lía Nattero-Chávez; Sandra Redondo López; Sara Alonso Díaz; Marta Garnica Ureña; Elena Fernández-Durán ...   In patients with type 1 diabetes, peripheral arterial stiffness defined by the ABI is associated with cardiovascular neuropathy independent of the presence of peripheral arterial disease.     Bile Modulates Secretion of Incretins and Insulin: A Study of Human Extrahepatic Cholestasis     Teresa Mezza; Simona Moffa; Pietro Manuel Ferraro; Giuseppe Quero ; Umberto Capece...   Acute alteration in bile flow in nondiabetic humans is associated with hyperglycemia, impaired insulin secretion capacity, increased glucagon and GLP-1 secretion, and a reduction in GIP secretion.     Central Precocious Puberty as a Presenting Sign of Nonclassical Congenital Adrenal Hyperplasia: Clinical Characteristics     Bar Neeman; Rachel Bello; Liora Lazar; Moshe Phillip ; Liat de Vries   Girls presenting with CPP underwent GnRH and ACTH tests. NCCAH was found in 4.8% of girls with CPP. No single parameter could differentiate between NCCAH and idiopathic CPP.     Climacteric Status at the Age of 46: Impact on Metabolic Outcomes in Population-Based Study     Susanna Savukoski; Hannele Mäkelä; Juha Auvinen; Jari Jokelainen ; Katri Puukka ...   Cardiovascular disease -associated risk factors were investigated in women, in relation to climacterium status at the age of 46, finding mainly adverse changes in climacteric women.     Leukocyte Telomere Length and Risk of Papillary Thyroid Carcinoma     Ji Li; Changming An; Haitao Zheng; Tianshui Lei ; Nasha Zhang ...   We report that telomere length contributes to predisposition to papillary thyroid cancer (PTC). There is a reverse U-shaped association between telomere length and PTC risk.     Contribution of Liver Fat to Weight Loss–Induced Changes in Serum Hepatokines: A Randomized Controlled Trial     Ine Telgenkamp; Yvo H A M Kusters; Casper G Schalkwijk; Alfons J H M Houben ; M Eline Kooi ...   In a randomized, controlled weight-loss intervention trial, the change in serum IGF1—but not IGFBP1, SHBG, FGF21, fetuin A, and fetuin B—was mediated by the change in intrahepatic triglyceride content.     Changes of Vitamin D-Binding Protein, and Total, Bioavailable, and Free 25-Hydroxyvitamin D in Transgender People     Hailing Chen; Chantal M Wiepjes; Natasja M van Schoor; Annemieke C Heijboer ; Renate T de Jongh ...   DBP tended to increase in transwomen, but not in transmen. Total, bioavailable, and free 25(OH)D did not change. Total 25(OH)D was well correlated with bioavailable and free 25(OH)D.     Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study     Christine E Hofmann ; Paul Harmatz; Jerry Vockley; Wolfgang Högler; Hideki Nakayama...   Most infants and young children with hypophosphatasia, treated with asfotase alfa, showed improved skeletal manifestations, respiratory function, and growth within 1 year, maintained up to 6 years.     Quality of Life in Hypoparathyroidism Improves With rhPTH(1-84) Throughout 8 Years of Therapy     Gaia Tabacco; Yu-Kwang Donovan Tay; Natalie E Cusano; John Williams ; Beatriz Omeragic ...   rhPTH(1-84) improves QOL in hypoparathyroid patients especially in those with reduced baseline scores, shorter duration of disease, and in those whose conventional therapy requirements decreased.     Altered Thyroid Function and Structure in Children and Adolescents Who Are Overweight and Obese: Reversal After Weight Loss     Maria Rosaria Licenziati; Giuliana Valerio; Ilaria Vetrani ; Gaetano De Maria; Fabrizia Liotta ...   Obese children show alterations of thyroid structure and function that ameliorate or even normalize after significant weight loss. This underlies its functional nature.     Enteroendocrine Connections in Congenital Isolated GH Deficiency Due to a GHRH Receptor Gene Mutation     Alécia A Oliveira-Santos; Roberto Salvatori; Monica C Nogueira; Ana C Bueno ; Cynthia S Barros-Oliveira ...   In response to a mixed meal, subjects with isolated GH deficiency have blunted ghrelin suppression and secrete more GLP-1.     Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later     Nina Kaseva; Marja Vääräsmäki; Jouko Sundvall ; Hanna-Maria Matinolli; Marika Sipola ...   We measured cardiometabolic markers in offspring of mothers with GDM, prepregnancy overweight, and controls. GDM was, unlike maternal overweight, linked with unhealthier cardiometabolic profiles.     Timing Modulates the Effect of Sleep Loss on Glucose Homeostasis     Britta Wilms; Rodrigo Chamorro; Manfred Hallschmid; Denisa Trost ; Nelli Forck ...   We analyzed the timing of sleep loss on glucose homeostasis. Sleep loss per se impairs glucose homeostasis, whereas early-morning sleep loss further compromises α-cell and HPA axis activity.     Depression Over the Lifespan in a Population-Based Cohort of Women With Polycystic Ovary Syndrome: Longitudinal Analysis     Eleni A Greenwood; Kristine Yaffe; Melissa F Wellons; Marcelle I Cedars ; Heather G Huddleston   In a population-based cohort of 1127 women, depression scores were higher across the lifespan in women with polycystic ovary syndrome (PCOS) however declined with aging in a trajectory similar to that in women without PCOS.     Effects of Estrogen Therapies on Outcomes in Turner Syndrome: Assessment of Induction of Puberty and Adult Estrogen Use     Antoinette Cameron-Pimblett; Melanie C Davies; Elizabeth Burt; Vikram Sinai Talaulikar ; Clementina La Rosa ...   We assessed the association between the timing of induction of puberty or type of estrogen replacement therapy preparations on health outcomes in adults with Turner syndrome.     Exome Sequencing Reveals the POLR3H Gene as a Novel Cause of Primary Ovarian Insufficiency     Monica M Franca; Xingfa Han; Mariana F A Funari; Antonio M Lerario ; Mirian Y Nishi ...   This study revealed the first POLR3H mutation in two unrelated families with POI. The animal model showed delayed pubertal development and decreased fertility.     Mild Physiologic Hyperglycemia Induces Hepatic Insulin Resistance in Healthy Normal Glucose-Tolerant Participants     Devjit Tripathy; Aurora Merovci; Rita Basu; Muhammad Abdul-Ghani ; Ralph A DeFronzo   This study examined the effect of mild physiologic hyperglycemia (40 mg/dL) for 48 hours in healthy glucose-tolerant participants with and without FH of type 2 diabetes.     Functional Genetic Variation in the Anti-Müllerian Hormone Pathway in Women With Polycystic Ovary Syndrome     Lidija K Gorsic; Matthew Dapas; Richard S Legro; M Geoffrey Hayes ; Margrit Urbanek   Functional characterization of genetic variation in AMH and its cognate receptor, AMHR2, in women with PCOS provides strong evidence for the role of impaired AMH signaling in the pathology of PCOS.     Associations of Outdoor Temperature, Bright Sunlight, and Cardiometabolic Traits in Two European Population-Based Cohorts     Raymond Noordam; Ashna Ramkisoensing; Nellie Y Loh ; Matt J Neville; Frits R Rosendaal ...   Outdoor temperature and sunlight were studied in relationship to cardiometabolic traits, and it was found that specifically outdoor sunlight showed beneficial associations with insulin resistance.     Individuals With Prediabetes Display Different Age-Related Pathophysiological Characteristics     Teresa Vanessa Fiorentino; Elisabetta Pedace; Elena Succurro; Francesco Andreozzi ; Maria Perticone ...   A total of 1418 subjects underwent an OGTT to evaluate glucose tolerance, insulin secretion, and sensitivity. We found different age-related metabolic phenotypes among subjects with IFG or IGT.     Truncating RAX Mutations: Anophthalmia, Hypopituitarism, Diabetes Insipidus, and Cleft Palate in Mice and Men     Cécile Brachet; Elena A Kozhemyakina; Emese Boros; Claudine Heinrichs ; Irina Balikova...   Homozygous truncating RAX mutations in a child, not only cause anophthalmia, but also hypopituitarism, diabetes insipidus, and cleft lip and palate, similar to the Rax knock-out mouse endocrine phenotype.     Risk of Incident Dementia According to Metabolic Health and Obesity Status in Late Life: A Population-Based Cohort Study     Ji-Yeon Lee; Kyungdo Han; Eugene Han; Gyuri Kim ; Hanna Cho ...   This large, population-based study analyzed 5,669,488 adults >60 years old and found that the metabolically healthy obese phenotype in late life is associated with lower risk of overall dementia.     Separate and Combined Effects of GIP and GLP-1 Infusions on Bone Metabolism in Overweight Men Without Diabetes     Natasha Chidekel Bergmann; Asger Lund; Lærke Smidt Gasbjerg; Niklas Rye Jørgensen ; Lene Jessen ...   In overweight men, infusion of GIP and GLP-1 decreased bone resorption, and coinfusion of the two incretins had partially additive effects on bone resorption.     Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity     Maria Caterina De Rosa; Alessandra Chesi; Shana McCormack ; Justin Zhou; Benjamin Weaver ...   This study identifies pathogenic variants in the MC4R gene in children with severe early-onset obesity from African American race and Latino ancestry.       Commentary       Genetic Testing for the Child With Short Stature—Has the Time Come To Change Our Diagnostic Paradigm?     Andrew Dauber   Genetic testing is rapidly becoming a primary means of diagnosis for patients with short stature.       Corrections       CORRIGENDUM FOR “Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men”         ERRATUM FOR “PTHrP-Mediated Hypercalcemia: Causes and Survival in 138 Patients”

Print Abstracts—Full Content Online Only         Clinical Research Articles       Impact of Pubertal Maturation and Chronologic Age on Sex Steroids in Peripubertal Girls     Frank M Biro; Bin Huang; Donald Walt Chandler; Cecily L Fassler; Susan M Pinney   Sex steroid levels were followed longitudinally in a group of peripubertal girls. Age and puberty made unique contributions to estrogen levels.     Disparate Effect of Aromatization on the Central Regulation of GH Secretion by Estrogens in Men and Postmenopausal Women     Vita Birzniece; Mark McLean; Navneeta Reddy; Ken K Y Ho   Aromatase inhibition significantly reduced GH secretion and circulating estradiol in men but not postmenopausal women, indicating that estrogen is unlikely to mediate GH secretion in menopause.     Long-Term Outcome of Primary Bilateral Macronodular Adrenocortical Hyperplasia After Unilateral Adrenalectomy     Andrea Osswald; Marcus Quinkler; Guido Di Dalmazi; Timo Deutschbein ; German Rubinstein ...   Unilateral adrenalectomy in primary bilateral macronodular adrenocortical hyperplasia leads to a lower rate of adrenal insufficiency but also to less sufficient biochemical control of hypercortisolism.     Assessment of a Multidisciplinary Intervention in Patients With BMI ≥35 kg/m2 and Recently Diagnosed Type 2 Diabetes     Ana Cristina García-Ulloa; Victoria Landa-Anell; Marco Melgarejo-Hernández ; Andrea Villegas-Narvaez; Luz Elena Urbina-Arronte ...   The Center of Comprehensive Care for the Patient with Diabetes achieves metabolic control in short and intermediate terms. Results show no difference at 1 year in a cohort of patients with obesity.     Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome     Ayca Erkin-Cakmak; Yasmin Bains; Russell Caccavello ; Susan M Noworolski; Jean-Marc Schwarz ...   Nine days of isocaloric fructose restriction in children with obesity and metabolic syndrome reduced d-lactate levels, de novo lipogenesis, and liver fat content while improving insulin sensitivity.     Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease     Rae-Chi Huang; Karen A Lillycrop; Lawrence J Beilin ; Keith M Godfrey; Denise Anderson...   An estimate of biological age determined from peripheral blood DNA from ∼1000 adolescents may refine prediction of cardiovascular risk above and beyond traditional risk factors.     Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes     Fang Fang; Meng-Yu Lai; Jing-Jing Huang; Mei Kang ; Ming-Ming Ma ...   Enhanced hippocampal functional connectivity occurring prior to structural changes was found in young adults with T2DM, suggesting an adaptive brain compensation to counteract cognitive decrements.     Association Between Age at Natural Menopause and Risk of Type 2 Diabetes in Postmenopausal Women With and Without Obesity     Jiajia Jiang; Jia Cui; Anping Wang; Yiming Mu ; Yuxiang Yan ...   Postmenopausal obesity status may influence the association between age at natural menopause and the development of T2DM.