Journal of Clinical Endocrinology and Metabolism : JCEM




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SGLT2 Inhibitor–Induced Low-Grade Ketonemia Ameliorates Retinal Hypoxia in Diabetic Retinopathy—A Novel Hypothesis

Sunder Mudaliar, Christopher Hupfeld, Daniel L Chao

doi : 10.1210/clinem/dgab050

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1235–1244

Diabetic retinopathy (DR) is a well-recognized microvascular complication of diabetes. Growing evidence suggests that, in addition to retinal vascular damage, there is significant damage to retinal neural tissue in DR. Studies reveal neuronal damage before clinically evident vascular lesions and DR is now classified as a neurovascular complication. Hyperglycemia causes retinal damage through complex metabolic pathways leading to oxidative stress, inflammation, vascular damage, capillary ischemia, and retinal tissue hypoxia. Retinal hypoxia is further worsened by high oxygen consumption in the rods. Persistent hypoxia results in increases in vascular endothelial growth factor (VEGF) and other pro-angiogenic factors leading to proliferative DR/macular edema and progressive visual impairment. Optimal glucose control has favorable effects in DR. Other treatments for DR include laser photocoagulation, which improves retinal oxygenation by destroying the high oxygen consuming rods and their replacement by low oxygen consuming glial tissue. Hypoxia is a potent stimulator of VEGF, and intravitreal anti-VEGF antibodies are effective in regressing macular edema and in some studies, retinal neovascularization. In this review, we highlight the complex pathophysiology of DR with a focus on retinal oxygen/fuel consumption and hypoxic damage to retinal neurons. We discuss potential mechanisms through which sodium-glucose cotransporter 2 (SGLT2) inhibitors improve retinal hypoxia—through ketone bodies, which are energetically as efficient as glucose and yield more ATP per molecule of oxygen consumed than fat, with less oxidative stress. Retinal benefits would occur through improved fuel energetics, less hypoxia and through the anti-inflammatory/oxidative stress effects of ketone bodies. Well-designed studies are needed to explore this hypothesis.

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Menopausal Hormone Therapy and Cardiovascular Disease: The Role of Formulation, Dose, and Route of Delivery

Chrisandra L Shufelt, JoAnn E Manson

doi : 10.1210/clinem/dgab042

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1245–1254

This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery.

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Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes 

Jingya Wang, Jennifer M Cooper, Krishna Gokhale, Dionisio Acosta-Mena, Samir Dhalla, Nathan Byne, Joht Singh Chandan, Astha Anand, Kelvin Okoth, Anuradhaa Subramanian, Mansoor N Bangash, Thomas Jackson, Dawit Zemedikun, Tom Taverner, Wasim Hanif, Sandip Ghosh, Parth Narendran, Konstantinos A Toulis, Abd A Tahrani, Rajendra Surenthirakumaran, Nicola J Adderley, Shamil Haroon, Kamlesh Khunti, Christopher Sainsbury, G Neil Thomas, Krishnarajah Nirantharakumar

doi : 10.1210/clinem/dgab067

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1255–1268

Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.

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Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes 

Evdoxia Bletsa, Sebastien Filippas-Dekouan, Christina Kostara, Panagiotis Dafopoulos, Aikaterini Dimou, Eleni Pappa, Styliani Chasapi, Georgios Spyroulias, Anastasios Koutsovasilis, Eleni Bairaktari, Ele Ferrannini, Vasilis Tsimihodimos

doi : 10.1210/clinem/dgab086

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1269–1283

Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate.

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Cardiovascular Disease in Patients With Primary and Secondary Adrenal Insufficiency and the Role of Comorbidities

Kanchana Ngaosuwan, Desmond G Johnston, Ian F Godsland, Jeremy Cox, Azeem Majeed, Jennifer K Quint, Nick Oliver, Stephen Robinson

doi : 10.1210/clinem/dgab063

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1284–1293

Mortality studies have established that cardiovascular disease is the leading cause of death in patients with adrenal insufficiency and the risk is greater than that observed in individually matched controls.

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Improvement in A1c Levels in Early Adulthood in the T1D Exchange: Impact of Racial, Socioeconomic, and Clinical Factors

Elena Toschi, Ryan J Bailey, Kellee M Miller, Peter M Calhoun

doi : 10.1210/clinem/dgab077

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1294–1302

Glycemic control in adolescents with type 1 diabetes is poor; yet, it typically improves during early adulthood. Factors related to improvement of glycemic control are unclear.

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Vertebral Fracture Assessment in Postmenopausal Women With Postsurgical Hypoparathyroidism

Cristiana Cipriani, Salvatore Minisola, John P Bilezikian, Davide Diacinti, Luciano Colangelo, Valentina Piazzolla, Maurizio Angelozzi, Luciano Nieddu, Jessica Pepe, Daniele Diacinti

doi : 10.1210/clinem/dgab076

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1303–1311

Hypoparathyroidism is a rare endocrine disorder whose skeletal features include suppression of bone turnover and greater volume and width of the trabecular compartment. Few and inconsistent data are available on the prevalence of vertebral fractures (VF).

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Differential Mitochondrial Gene Expression in Adipose Tissue Following Weight Loss Induced by Diet or Bariatric Surgery 

Birgitta W van der Kolk, Maheswary Muniandy, Dorota Kaminska, Marcus Alvarez, Arthur Ko, Zong Miao, Armand Valsesia, Dominique Langin, Maija Vaittinen, Mirva P??kk?nen, Riikka Jokinen, Sanna Kaye, Sini Heinonen, Kirsi A Virtanen, Daniel P Andersson, Ville M?nnist?, Wim H Saris, Arne Astrup, Mikael Rydén, Ellen E Blaak, P?ivi Pajukanta, Jussi Pihlajam?ki, Kirsi H Pietil?inen

doi : 10.1210/clinem/dgab072

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1312–1324

Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.

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Statins Decrease the Risk of Orbitopathy in Newly Diagnosed Patients with Graves Disease

Anton Nilsson, Kleoniki Tsoumani, Tereza Planck

doi : 10.1210/clinem/dgab070

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1325–1332

The aim of this study was to examine the effect of statins and other lipid-lowering agents on the development of Graves orbitopathy (GO) in patients with newly diagnosed Graves disease (GD).

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Identification and Clinical Associations of 3 Forms of Circulating T-cadherin in Human Serum 

Shiro Fukuda, Shunbun Kita, Kazuya Miyashita, Masahito Iioka, Jun Murai, Tadashi Nakamura, Hitoshi Nishizawa, Yuya Fujishima, Jun Morinaga, Yuichi Oike, Norikazu Maeda, Iichiro Shimomura

doi : 10.1210/clinem/dgab066

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1333–1344

T-cadherin (T-cad) is a glycosylphosphatidylinositol (GPI)-anchored cadherin that mediates adiponectin to induce exosome biogenesis and secretion, protect cardiovascular tissues, promote muscle regeneration, and stimulate therapeutic heart protection by transplanted mesenchymal stem cells. CDH13, the gene locus of T-cad, affects plasma adiponectin levels most strongly, in addition to affecting cardiovascular disease risk and glucose homeostasis. Recently, it has been suggested that T-cad exists in human serum, although the details are still unclear.

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Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial 

Matthew C Riddle, Hertzel C Gerstein, Denis Xavier, William C Cushman, Lawrence A Leiter, Peter J Raubenheimer, Charles M Atisso, Sohini Raha, Oralee J Varnado, Manige Konig, Mark Lakshmanan, Edward Franek

doi : 10.1210/clinem/dgab065

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1345–1351

Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.

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Total and Central Adiposity Are Associated With Age at Gonadarche and Incidence of Precocious Gonadarche in Boys

Ana Pereira, Alexander S Busch, Fernanda Solares, Ingrid Baier, Camila Corvalan, Veronica Mericq

doi : 10.1210/clinem/dgab064

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1352–1361

A close link between body mass index (BMI) and female pubertal onset is well established. However, observations in boys remain inconclusive.

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In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover

Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

doi : 10.1210/clinem/dgab061

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1362–1376

Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

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Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL) 

Sharon H Chou, Elle M Murata, Cindy Yu, Jacqueline Danik, Gregory Kotler, Nancy R Cook, Vadim Bubes, Samia Mora, Paulette D Chandler, Deirdre K Tobias, Trisha Copeland, Julie E Buring, JoAnn E Manson, Meryl S LeBoff

doi : 10.1210/clinem/dgaa981

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1377–1388

Although observational studies show inverse associations between vitamin D status and body weight/adiposity, there are few large randomized controlled trials (RCTs) investigating this relationship.

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The Age-Dependent Changes of the Human Adrenal Cortical Zones Are Not Congruent

Yuta Tezuka, Nanako Atsumi, Amy R Blinder, Juilee Rege, Thomas J Giordano, William E Rainey, Adina F Turcu

doi : 10.1210/clinem/dgab007

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1389–1397

While previous studies indicate that the zonae reticularis (ZR) and glomerulosa (ZG) diminish with aging, little is known about age-related transformations of the zona fasciculata (ZF).

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Impaired Suppression of Glucagon in Obese Subjects Parallels Decline in Insulin Sensitivity and Beta-Cell Function

Xi Chen, Enrique Maldonado, Ralph A DeFronzo, Devjit Tripathy

doi : 10.1210/clinem/dgab019

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1398–1409

To examine the relationship between plasma glucagon levels and insulin sensitivity and insulin secretion in obese subjects.

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Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

Dong Chen, Yawen Tan, Zhichao Li, Wujiao Li, Lei Yu, Wei Chen, Yuchen Liu, Lisa Liu, Liangfeng Guo, Weiren Huang, Yongsheng Zhao

doi : 10.1210/clinem/dgab020

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1410–1426

Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors.

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Maternal Oxidative Stress Biomarkers in Pregnancy and Child Growth from Birth to Age 6

Olufunmilayo Arogbokun, Emma Rosen, Alexander P Keil, Ginger L Milne, Emily Barrett, Ruby Nguyen, Nicole R Bush, Shanna H Swan, Sheela Sathyanarayana, Kelly K Ferguson

doi : 10.1210/clinem/dgab018

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1427–1436

Maternal oxidative stress in pregnancy can arise through a multitude of sources and may have lifelong consequences for the child. Animal studies suggest that prenatal oxidative stress may contribute to metabolic dysfunction and excessive weight gain in the offspring. However, this relationship has been studied minimally in humans.

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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans

Emmani B M Nascimento, Michiel P B Moonen, Carlijn M E Remie, Karim Gariani, Johanna A J?rgensen, Gert Schaart, Joris Hoeks, Johan Auwerx, Wouter D van Marken Lichtenbelt, Patrick Schrauwen

doi : 10.1210/clinem/dgaa960

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1437–1447

Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance.

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18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients

Xin He, Elaine M Caoili, Anca M Avram, Barbra S Miller, Tobias Else

doi : 10.1210/clinem/dgab005

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1448–1459

Adrenal tumors in noncancer patients are common.

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A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome

Marietta Rottenkolber, Christina Gar, Cornelia Then, Lorena Wanger, Vanessa Sacco, Friederike Banning, Anne L Potzel, Stefanie Kern-Matschilles, Claudia Nevinny-Stickel-Hinzpeter, Harald Grallert, Nina Hesse, Jochen Seissler, Andreas Lechner

doi : 10.1210/clinem/dgab057

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1460–1471

Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we re-evaluated this hypothesis.

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Robust Neutralizing Antibodies to SARS-CoV-2 Develop and Persist in Subjects with Diabetes and COVID-19 Pneumonia 

Stefania Dispinseri, Vito Lampasona, Massimiliano Secchi, Andrea Cara, Elena Bazzigaluppi, Donatella Negri, Cristina Brigatti, Maria Franca Pirillo, Ilaria Marzinotto, Martina Borghi, Patrizia Rovere-Querini, Cristina Tresoldi, Fabio Ciceri, Marina Scavini, Gabriella Scarlatti, Lorenzo Piemonti

doi : 10.1210/clinem/dgab055

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1472–1481

Demonstrating the ability to mount a neutralizing antibody response to SARS-CoV-2 in the presence of diabetes is crucial to understand COVID-19 pathogenesis, reinfection potential, and vaccine development.

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Genotype-Phenotype Correlation in Fibrous Dysplasia/McCune-Albright Syndrome

Maria Zhadina, Kelly L Roszko, Raya E S Geels, Luis F de Castro, Michael T Collins, Alison M Boyce

doi : 10.1210/clinem/dgab053

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1482–1490

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood.

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Long-term Effect of Aromatase Inhibition in Aromatase Excess Syndrome

Gerhard Binder, Akie Nakamura, Roland Schweizer, Tsutomu Ogata, Maki Fukami, Keisuke Nagasaki

doi : 10.1210/clinem/dgab054

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1491–1500

Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens.

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Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals

Sriram Gubbi, Ranganath Muniyappa, Susmeeta T Sharma, Shivraj Grewal, Raven McGlotten, Lynnette K Nieman

doi : 10.1210/clinem/dgab046

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1501–1515

Increased tissue cortisol availability has been implicated in abnormal glucose and fat metabolism in patients with obesity, metabolic syndrome, and type 2 diabetes (T2DM). Our objective was to evaluate whether blockade of glucocorticoid receptor (GR) with mifepristone ameliorates insulin resistance (IR) in overweight/obese subjects with glucose intolerance.

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Characterization and Proteomic Analysis of Endometrial Stromal Cell–Derived Small Extracellular Vesicles

Chia-Yi Hsu, Tsung-Hua Hsieh, Hsiao-Yun Lin, Chi-Yu Lu, Hui-Wen Lo, Ching-Chou Tsai, Eing-Mei Tsai

doi : 10.1210/clinem/dgab045

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1516–1529

Small extracellular vesicles (sEVs) have emerged as modulators of the disease microenvironment, thereby supporting disease progression. However, the potential role of EVs and their content to the pathophysiology of endometriosis remain unclear.

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Approach to the Virilizing Girl at Puberty 

Maristella Santi, Stefanie Graf, Mazen Zeino, Martine Cools, Koen Van De Vijver, Mafalda Trippel, Nijas Aliu, Christa E Flück

doi : 10.1210/clinem/dgaa948

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages 1530–1539

Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as “premature adrenarche.” It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene.

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Metastatic Pheochromocytomas and Abdominal Paragangliomas 

Dan Granberg, Carl Christofer Juhlin, Henrik Falhammar

doi : 10.1210/clinem/dgaa982

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e1937–e1952

Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behavior.

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Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review

Jordan E Perlman, Philip C Johnston, Ferdinand Hui, Guy Mulligan, Robert J Weil, Pablo F Recinos, Divya Yogi-Morren, Roberto Salvatori, Debraj Mukherjee, Gary Gallia, Laurence Kennedy, Amir H Hamrahian

doi : 10.1210/clinem/dgab012

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e1953–e1967

Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases.

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The Role of Metabolic Syndrome and its Components in Incident Fracture: A 15-Year Follow-Up Among the Iranian Population

Atieh Amouzegar, Samaneh Asgari, Fereidoun Azizi, Amir Abbas Momenan, Mohammadreza Bozorgmanesh, Farzad Hadaegh

doi : 10.1210/clinem/dgab023

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e1968–e1983

The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate.

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Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease

Daniel I Weiman, Farid H Mahmud, Antoine B M Clarke, Esther Assor, Charlotte McDonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Margaret A Marcon, CD-DIET Study Group

doi : 10.1210/clinem/dgaa977

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e1984–e1992

Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD.

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Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes

Emilia Huvinen, Anna-Kaisa Tuomaala, Paula H Bergman, Jelena Meinil?, Tuija Tammelin, Janne Kulmala, Elina Engberg, Saila B Koivusalo

doi : 10.1210/clinem/dgaa979

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e1993–e2004

Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown.

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Dyslipidemia, Insulin Resistance, Ectopic Lipid Accumulation, and Vascular Function in Resistance to Thyroid Hormone ? 

Carla Moran, Carmel M McEniery, Nadia Schoenmakers, Catherine Mitchell, Alison Sleigh, Laura Watson, Greta Lyons, Keith Burling, Peter Barker, Krishna Chatterjee

doi : 10.1210/clinem/dgab002

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2005–e2014

In resistance to thyroid hormone due to mutations in thyroid hormone receptor ?, peripheral tissues are variably refractory to the action of circulating thyroid hormones. We evaluated parameters contributing to atherosclerotic risk in this disorder.

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Cardiometabolic Profile of Different Body Composition Phenotypes in Children

Yi Ying Ong, Jonathan Y Huang, Navin Michael, Suresh Anand Sadananthan, Wen Lun Yuan, Ling-Wei Chen, Neerja Karnani, S Sendhil Velan, Marielle V Fortier, Kok Hian Tan, Peter D Gluckman, Fabian Yap, Yap-Seng Chong, Keith M Godfrey, Mary F-F Chong, Shiao-Yng Chan, Yung Seng Lee, Mya-Thway Tint, Johan G Eriksson

doi : 10.1210/clinem/dgab003

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2015–e2024

Cardiometabolic profiles of different body composition phenotypes are poorly characterized in young children, where it is well established that high adiposity is unfavorable, but the role of lean mass is unclear.

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Postconvalescent SARS-CoV-2 IgG and Neutralizing Antibodies are Elevated in Individuals with Poor Metabolic Health 

Sabrina E Racine-Brzostek, He S Yang, Gwendolyne A Jack, Zhengming Chen, Amy Chadburn, Thomas J Ketas, Erik Francomano, P J Klasse, John P Moore, Kathleen A McDonough, Roxanne C Girardin, Alan P Dupuis, II, Anne F Payne, Lucy X Ma, Jacob Sweeney, Elaine Zhong, Jim Yee, Melissa M Cushing, Zhen Zhao

doi : 10.1210/clinem/dgab004

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2025–e2034

Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess.

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Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality

Marie Helene Schernthaner-Reiter, Christina Siess, Alexander Micko, Christian Zauner, Stefan Wolfsberger, Christian Scheuba, Philipp Riss, Engelbert Knosp, Alexandra Kautzky-Willer, Anton Luger, Greisa Vila

doi : 10.1210/clinem/dgab058

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2035–e2046

Cushing syndrome (CS) results in significant morbidity and mortality.

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Lactation Induction in a Transgender Woman Wanting to Breastfeed: Case Report

Rachel Wamboldt, Shirley Shuster, Bikrampal S Sidhu

doi : 10.1210/clinem/dgaa976

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2047–e2052

Breastfeeding is known to have many health and wellness benefits to the mother and infant; however, breastfeeding in trans women has been greatly under-researched.

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Prevalence and Features of Impaired Glucose Tolerance in Young Underweight Japanese Women

Motonori Sato, Yoshifumi Tamura, Takashi Nakagata, Yuki Someya, Hideyoshi Kaga, Nozomu Yamasaki, Mai Kiya, Satoshi Kadowaki, Daisuke Sugimoto, Hiroaki Satoh, Ryuzo Kawamori, Hirotaka Watada

doi : 10.1210/clinem/dgab052

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2053–e2062

In Japan, while it is known that underweight women over the age of 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we investigate the prevalence and features of impaired glucose tolerance (IGT) in young underweight Japanese women.

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Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia 

Deborah P Merke, Ashwini Mallappa, Wiebke Arlt, Aude Brac de la Perriere, Angelica Lindén Hirschberg, Anders Juul, John Newell-Price, Colin G Perry, Alessandro Prete, D Aled Rees, Nicole Reisch, Nike Stikkelbroeck, Philippe Touraine, Kerry Maltby, F Peter Treasure, John Porter, Richard J Ross

doi : 10.1210/clinem/dgab051

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2063–e2077

Standard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes.

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Dietary Pattern Trajectories from Youth to Adulthood and Adult Risk of Impaired Fasting Glucose: A 31-year Cohort Study

Feitong Wu, Katja Pahkala, Markus Juonala, Suvi P Rovio, Matthew A Sabin, Tapani R?nnemaa, Marie-Jeanne Buscot, Kylie J Smith, Satu M?nnist?, Antti Jula, Terho Lehtim?ki, Nina Hutri-K?h?nen, Mika K?h?nen, Tomi Laitinen, Jorma S A Viikari, Olli T Raitakari, Costan G Magnussen

doi : 10.1210/clinem/dgab044

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2078–e2086

The influence of dietary pattern trajectories from youth to adulthood on adult glucose metabolism is unknown.

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Adrenal Venous Sampling in Young Patients with Primary Aldosteronism. Extravagance or Irreplaceable?

Eleftheria Gkaniatsa, Augustinas Sakinis, Magnus Palmér, Andreas Muth, Penelope Trimpou, Oskar Ragnarsson

doi : 10.1210/clinem/dgab047

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2087–e2095

Current clinical guidelines suggest that adrenal venous sampling (AVS) may not be mandatory in young patients with primary aldosteronism (PA) and a solitary adrenal adenoma on imaging.

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Daytime Napping Duration Is Positively Associated With Risk of Hyperuricemia in a Chinese Population

Yanjiao Wang, Yongli Zeng, Xuehui Zhang, Qiong Meng, Fei Mi, Songmei Wang, Fang Xu, Yan Sun, Yuemei Feng, Jianzhong Yin

doi : 10.1210/clinem/dgab043

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2096–e2105

Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia.

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Association of Diabetes Subgroups With Race/Ethnicity, Risk Factor Burden and Complications: The MASALA and MESA Studies 

Michael P Bancks, Alain G Bertoni, Mercedes Carnethon, Haiying Chen, Mary Frances Cotch, Unjali P Gujral, David Herrington, Alka M Kanaya, Moyses Szklo, Dhananjay Vaidya, Namratha R Kandula

doi : 10.1210/clinem/dgaa962

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2106–e2115

There are known disparities in diabetes complications by race and ethnicity. Although diabetes subgroups may contribute to differential risk, little is known about how subgroups vary by race/ethnicity.

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Effect of a Multifactorial Intervention on Fracture in Patients With Type 2 Diabetes: Subanalysis of the J-DOIT3 Study 

Takayoshi Sasako, Kohjiro Ueki, Kana Miyake, Yukiko Okazaki, Yasuhiro Takeuchi, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki

doi : 10.1210/clinem/dgab013

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2116–e2128

To evaluate the effects of an intensified multifactorial intervention and patient characteristics on the incidence of fractures comorbid with type 2 diabetes.

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Relationship of Preoperative Thyroid Dysfunction to Clinical Outcomes in Pediatric Cardiac Surgery

Morgan L Brown, Luis G Quinonez, Steven J Staffa, James A DiNardo, Ari J Wassner

doi : 10.1210/clinem/dgab040

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2129–e2136

Thyroid function may be assessed in children before cardiac surgery because of concerns that hypothyroidism or thyrotoxicosis might adversely affect cardiac function perioperatively. However, the relationship between preoperative thyroid dysfunction and surgical outcomes is unknown.

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Serum Follistatin Is Increased in Thyroid Cancer and Is Associated With Adverse Tumor Characteristics in Humans

Grigorios Panagiotou, Wael Ghaly, Jagriti Upadhyay, Kalliopi Pazaitou-Panayiotou, Christos S Mantzoros

doi : 10.1210/clinem/dgab041

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2137–e2150

Obesity and classical growth factors are associated with thyroid cancer (TC). However, less is known regarding novel hormones such as follistatins and activins. We hypothesized that serum follistatin but not activins would be increased in TC.

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Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS

Sarah E Hoover, Barbara A Gower, Yenni E Cedillo, Paula C Chandler-Laney, Sarah E Deemer, Amy M Goss

doi : 10.1210/clinem/dgab028

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2151–e2161

Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin.

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Potassium Concentration in Initial Fluid Therapy and In-Hospital Mortality of Patients with Diabetic Ketoacidosis

Akira Okada, Hayato Yamana, Kojiro Morita, Yukihito Sato, Satoko Yamaguchi, Kayo Ikeda Kurakawa, Nobuaki Michihata, Hiroki Matsui, Kiyohide Fushimi, Masaomi Nangaku, Toshimasa Yamauchi, Hideo Yasunaga, Takashi Kadowaki

doi : 10.1210/clinem/dgab029

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2162–e2175

Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality.

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Genetic Profiling of Orbital Fibroblasts from Patients with Graves’ Orbitopathy

Giovanna Rotondo Dottore, Ilaria Bucci, Giulia Lanzolla, Iacopo Dallan, Angela Sframeli, Liborio Torregrossa, Giamberto Casini, Fulvio Basolo, Michele Figus, Marco Nardi, Claudio Marcocci, Michele Marin?

doi : 10.1210/clinem/dgab035

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2176–e2190

Graves’ orbitopathy (GO) is an autoimmune disease that persists when immunosuppression is achieved. Orbital fibroblasts from GO patients display peculiar phenotypes even if not exposed to autoimmunity, possibly reflecting genetic or epigenetic mechanisms, which we investigated here.

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Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L

Nicole Lafontaine, Purdey J Campbell, Juan E Castillo-Fernandez, Shelby Mullin, Ee Mun Lim, Phillip Kendrew, Michelle Lewer, Suzanne J Brown, Rae-Chi Huang, Phillip E Melton, Trevor A Mori, Lawrence J Beilin, Frank Dudbridge, Tim D Spector, Margaret J Wright, Nicholas G Martin, Allan F McRae, Vijay Panicker, Gu Zhu, John P Walsh, Jordana T Bell, Scott G Wilson

doi : 10.1210/clinem/dgaa975

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2191–e2202

Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited.

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Glucose Metabolism After Pancreatectomy: Opposite Extremes Between Pancreaticoduodenectomy and Distal Pancreatectomy 

Fumimaru Niwano, Naru Babaya, Yoshihisa Hiromine, Ippei Matsumoto, Keiko Kamei, Shinsuke Noso, Yasunori Taketomo, Yoshifumi Takeyama, Yumiko Kawabata, Hiroshi Ikegami

doi : 10.1210/clinem/dgab036

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2203–e2214

The rate of glucose metabolism changes drastically after partial pancreatectomy.

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Impaired Immune Function in Patients With Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study

Giulia Puliani, Valeria Hasenmajer, Francesca Sciarra, Federica Barbagallo, Emilia Sbardella, Riccardo Pofi, Daniele Gianfrilli, Elisabetta Romagnoli, Mary Anna Venneri, Andrea M Isidori

doi : 10.1210/clinem/dgab038

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2215–e2227

Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism.

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Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men

Mai Kiya, Yoshifumi Tamura, Kageumi Takeno, Yuki Someya, Saori Kakehi, Motonori Sato, Nozomu Yamasaki, Satoshi Kadowaki, Ruriko Suzuki, Yasuhiko Furukawa, Daisuke Sugimoto, Hideyoshi Kaga, Takashi Funayama, Miho Nishitani-Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Hiroaki Satoh, Ryuzo Kawamori, Hirotaka Watada

doi : 10.1210/clinem/dgab037

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2228–e2238

Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians.

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Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum

Alexandra H?pfinger, Martin Berghoff, Thomas Karrasch, Andreas Schmid, Andreas Sch?ffler

doi : 10.1210/clinem/dgaa983

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2239–e2250

Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain.

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Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study

Andreas Ebbehoj, Kirstine Stochholm, Sarah Forslund Jacobsen, Christian Trolle, Peter Jepsen, Maciej Grzegorz Robaczyk, ?se Krogh Rasmussen, Ulla Feldt-Rasmussen, Reimar Wernich Thomsen, Esben S?ndergaard, Per L?gstrup Poulsen

doi : 10.1210/clinem/dgaa965

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2251–e2261

Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare catecholamine-secreting tumors but recent studies suggest increasing incidence. Traditionally, PPGL are described to present with paroxysmal symptoms and hypertension, but existing data on clinical presentation of PPGL come from referral centers.

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Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules

Susmita Dutta, Soham Tarafdar, Pradip Mukhopadhyay, Nitai P Bhattacharyya, Sujoy Ghosh

doi : 10.1210/clinem/dgab030

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2262–e2270

Molecular testing is increasingly used to identify malignancy in thyroid nodules (especially indeterminate category). Measurement of cell-free DNA (cfDNA) levels from plasma has been useful in diagnosis of cancers of other organs/tissues; herein we analyze cfDNA levels in patients with thyroid nodules to explore the possibility of establishing a cutoff for identification of malignancy.

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Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes 

Praveer Sihota, Ram Naresh Yadav, Ruban Dhaliwal, Jagadeesh Chandra Bose, Vandana Dhiman, Deepak Neradi, Shailesh Karn, Sidhartha Sharma, Sameer Aggarwal, Vijay G Goni, Vishwajeet Mehandia, Deepak Vashishth, Sanjay Kumar Bhadada, Navin Kumar

doi : 10.1210/clinem/dgab027

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2271–e2289

Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue’s material properties obtained from individuals with diabetes and known fragility fracture status.

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Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition 

Maik Pietzner, Kathrin Budde, Malte Rühlemann, Henry V?lzke, Georg Homuth, Frank U Weiss, Markus M Lerch, Fabian Frost

doi : 10.1210/clinem/dgaa961

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2290–e2298

Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota.

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Paraneoplastic Secretion of Multiple Phosphatonins From a Deep Fibrous Histiocytoma Causing Oncogenic Osteomalacia 

Melvin Khee Shing Leow, Shaillay Dogra, Xiaojia Ge, Khoon Leong Chuah, Huiling Liew, Kelvin Siu Hoong Loke, Craig McFarlane

doi : 10.1210/clinem/dgaa964

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2299–e2308

Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor.

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Association Between Obstructive Sleep Apnea and Metabolic Abnormalities in Patients With Hypertrophic Cardiomyopathy 

Juan Wang, Haobo Xu, Jiansong Yuan, Chao Guo, Fenghuan Hu, Weixian Yang, Lei Song, Xiaoliang Luo, Rong Liu, Jingang Cui, Shengwen Liu, Yushi Chun, Shubin Qiao

doi : 10.1210/clinem/dgab015

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2309–e2321

Metabolic abnormalities have been associated with long-term cardiac mortality in patients with hypertrophic cardiomyopathy (HCM). Obstructive sleep apnea (OSA) is a risk factor for metabolic abnormalities in general populations, but association between OSA and metabolic abnormalities in HCM is still undefined. This study aimed to investigate the relationship between OSA and metabolic dysfunction in a large series of patients with HCM.

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Generation of ? Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene 

Silvia Pellegrini, Giovanni B Pipitone, Alessandro Cospito, Fabio Manenti, Gaia Poggi, Marta T Lombardo, Rita Nano, Gianvito Martino, Maurizio Ferrari, Paola Carrera, Valeria Sordi, Lorenzo Piemonti

doi : 10.1210/clinem/dgaa986

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2322–e2333

Maturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by ? cell failure. Induced pluripotent stem cells can differentiate into functional ? cells. Thus, ? cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy.

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A Set of Markers Related to Viral Infection Has a Sex-sensitive Prognostic Value in Papillary Thyroid Carcinoma

Dongyi Wan, Xin Yang, Ganxun Li, Yaying Du, Jing Cao, Yuan Gao, Zhiping Shu, Yu Zhou, Xiao Wei, Rong Guo, Runhua Zhang, Guopeng Zhang

doi : 10.1210/clinem/dgaa990

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2334–e2346

Although the incidence of papillary thyroid carcinoma (PTC) is significantly higher in females than in males, the prognosis of male PTC is more unfavorable. However, the cause of higher malignancy of PTC in male patients remains unclear.

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Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study 

Austin G Stack, David Han, Ronald Goldwater, Susanne Johansson, Nalina Dronamraju, Jan Oscarsson, Eva Johnsson, Joanna Parkinson, Fredrik Erlandsson

doi : 10.1210/clinem/dgaa748

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2347–e2356

Combining a sodium-glucose cotransporter 2 inhibitor with a xanthine oxidase inhibitor (XOI) and a urate transporter 1 (URAT1) inhibitor may enhance serum uric acid (sUA) lowering. However, concerns exist regarding high urinary UA (uUA) excretion rates and subsequent crystallization in renal tubules.

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From the Tip to the Iceberg Below—Evolving Our Molecular Understanding of Thyroid Nodules 

Erik K Alexander

doi : 10.1210/clinem/dgab087

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2357–e2358

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Correction of the Gene Defect in Cystic Fibrosis: Is It Too Late for Bone? 

Vin Tangpricha

doi : 10.1210/clinem/dgab074

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2359–e2361

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Diabetes Remission After Gastric Bypass: To Be or Not to Be Dependent on Weight Loss

Helen Lawler, Marzieh Salehi

doi : 10.1210/clinem/dgab008

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2362–e2364

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New Data to Challenge Gender-affirming Hormone Therapy Prescribing Practice

Tamar Reisman, Joshua D Safer

doi : 10.1210/clinem/dgab006

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2365–e2366

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The Use of IGF-I to Monitor Long-Acting Growth Hormone Therapy—Timing is an Art… 

Martin Bidlingmaier, Katharina Schilbach

doi : 10.1210/clinem/dgab016

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2367–e2369

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The Intriguing Intersection of Type 2 Diabetes, Obesity-Related Insulin Resistance, and Osteoarthritis 

David Bradley

doi : 10.1210/clinem/dgab009

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2370–e2372

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Does Early Identification of Central Congenital Hypothyroidism Result in Improved Outcomes?

Malcolm David Cairns Donaldson, Scott Dennis Grosse

doi : 10.1210/clinem/dgab059

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2373–e2375

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Letter to the Editor from Watanabe et al: “Long-term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study”

Hirotaka Watanabe, Mitsuyoshi Takahara, Naoto Katakami, Iichiro Shimomura

doi : 10.1210/clinem/dgab082

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2376–e2377

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Letter to the Editor from Chenyun Miao, et al: “Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome”

Chenyun Miao, Xiaojie Fang, Qin Zhang

doi : 10.1210/clinem/dgab021

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Pages e2378–e2379

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Corrigendum to: “Generation of ? Cells From iPSC of a MODY8 Patient With a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene” 

doi : 10.1210/clinem/dgab048

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 5, May 2021, Page e2380

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