Journal of Clinical Endocrinology and Metabolism : JCEM




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Proper Care of Transgender and Gender Diverse Persons in the Setting of Proposed Discrimination: A Policy Perspective* 

Abby Walch, Caroline Davidge-Pitts, Joshua D Safer, Ximena Lopez, Vin Tangpricha, Sean J Iwamoto

doi : 10.1210/clinem/dgaa816

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 305–308

Transgender and gender diverse (TGD) individuals face significant barriers to accessing health care. Recent introductions of regulatory policies at state and federal levels raise concerns over the politicization of gender-affirming health care, the risks of further restricting access to quality care, and the potential criminalization of healthcare professionals who care for TGD patients. The Endocrine Society and the Pediatric Endocrine Society have published several news articles and comments in the last couple of years supporting safe and effective gender-affirming interventions as outlined in the 2017 Endocrine Society’s Clinical Practice Guidelines. The Endocrine Society Position Statement on Transgender Health also acknowledges the rapid expansion in understanding the biological underpinning of gender identity and the need for increased funding to help close gaps in knowledge about the optimal care of TGD individuals. This Policy Perspective affirms these principles in the context of pending and future legislation attempting to discriminate against TGD patients while also stressing the need for science and health care experts to inform health policies.

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Skeletal Muscle and Metabolic Health: How Do We Increase Muscle Mass and Function in People with Type 2 Diabetes?

Ebaa Al-Ozairi, Dalal Alsaeed, Dherar Alroudhan, Nia Voase, Amal Hasan, Jason M R Gill, Naveed Sattar, Paul Welsh, Cindy M Gray, Jirapitcha Boonpor,Carlos Celis-Morales, Stuart R Gray 

doi : 10.1210/clinem/dgaa835

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 309–317

Whilst skeletal muscles’ primary role is allowing movement, it has important metabolic roles, including in glycemic control. Indeed, evidence indicates that low muscle mass and function are associated with an increased risk of type 2 diabetes, highlighting its importance in the development of metabolic disease.

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Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome

Marta Domènech, Elia Grau, Ares Solanes, Angel Izquierdo, Jes?s del Valle, Cristina Carrato, Marta Pineda, Nuria Due?as, Magda Pujol, Conxi L?zaro, Gabriel Capellà, Joan Brunet, Matilde Navarro

doi : 10.1210/clinem/dgaa833

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 318–325

Lynch syndrome (LS) is the most common inherited colorectal and endometrial cancer syndrome, caused by germline mutations in DNA mismatch repair (MMR) genes. It is also characterized by an increased risk of other tumors with lower prevalence, such as adrenal cortical carcinoma (ACC), an endocrine tumor with an incidence of <2 cases/million individuals/year. Most ACC developed during childhood are associated with hereditary syndromes. In adults, this association is not as well established as in children. Previous studies showed a 3.2% prevalence of LS among patients with ACC.

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Bone Metabolism in Adolescents Undergoing Bariatric Surgery

Madhusmita Misra, Miriam A Bredella

doi : 10.1210/clinem/dgaa836

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 326–336

The prevalence of childhood obesity has increased over past decades with a concomitant increase in metabolic and bariatric surgery (MBS). While MBS in adults is associated with bone loss, only a few studies have examined the effect of MBS on the growing skeleton in adolescents.

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Catecholestradiol Activation of Adrenergic Receptors Induces Endometrial Cell Survival via p38 MAPK Signaling

Rachel Sprague, Joung W Kim, Esma Kirimlioglu, Xiaofang Guo, Nihan Günay, Ozlem Guzeloglu-Kayisli, Asli Ozmen, Frederick Schatz, Anthony N Imudia, Charles J Lockwood, Ronald R Magness, Umit A Kayisli

doi : 10.1210/clinem/dgaa866

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 337–350

Enhanced levels of catecholestradiols, 2-hydroxyestradiol (2-OHE2) or 4-hydroxyestradiol (4-OHE2), are reported in endometriosis. During gestation, catecholestradiol activation of adrenergic receptors (AR) elevates estrogen receptor (ER)-independent proliferation of uterine arterial endothelial cells.

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Clinical Outcomes and Complications of Pituitary Blastoma

Anthony P Y Liu, Megan M Kelsey, Nelly Sabbaghian, Sung-Hye Park, Cheri L Deal, Adam J Esbenshade, Oswald Ploner, Andrew Peet, Heidi Traunecker, Yomna H E Ahmed, Margaret Zacharin, Anatoly Tiulpakov, Anastasia M Lapshina, Andrew W Walter, Pinaki Dutta, Ashutosh Rai, M?rta Korbonits, Leanne de Kock, Kim E Nichols, William D Foulkes, John R Priest

doi : 10.1210/clinem/dgaa857

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 351–363

Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome.

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Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia

Tejaswini Arunachala Murthy, Jacqueline Grivell, Seva Hatzinikolas, Lee-anne S Chapple, Marianne J Chapman, Julie E Stevens, Charles-Henri Malbert, Christopher K Rayner, Michael Horowitz, Karen L Jones, Chinmay S Marathe

doi : 10.1210/clinem/dgaa854

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 364–371

Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized “non-severe” hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. “Marked” hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of “mild” hypoglycemia (3.0-3.9 mmol/L) is unknown.

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A Noncoding Variant Near PPP1R3B Promotes Liver Glycogen Storage and MetS, but Protects Against Myocardial Infarction

Bratati Kahali, Yue Chen, Mary F Feitosa, Lawrence F Bielak, Jeffrey R O’Connell, Solomon K Musani, Yash Hegde, Yanhua Chen, L C Stetson, Xiuqing Guo, Yi-ping Fu, Albert Vernon Smith, Kathleen A Ryan, Gudny Eiriksdottir, Ariella T Cohain, Matthew Allison, Andrew Bakshi, Donald W Bowden, Matthew J Budoff, J Jeffrey Carr, Shannon Carskadon, Yii-Der I Chen, Adolfo Correa, Breland F Crudup, Xiaomeng Du, Tamara B Harris, Jian Yang, Sharon L R Kardia, Lenore J Launer, Jiankang Liu, Thomas H Mosley, Jr, Jill M Norris, James G Terry, Nallasivam Palanisamy, Eric E Schadt, Christopher J O’Donnell, Laura M Yerges-Armstrong, Jerome I Rotter, Lynne E Wagenknecht, Samuel K Handelman, Vilmundur Gudnason, Michael A Province, Patricia A Peyser, Brian Halligan, Nicholette D Palmer, Elizabeth K Speliotes

doi : 10.1210/clinem/dgaa855

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 372–387

Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation.

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Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes 

Melissa K Thomas, Amir Nikooienejad, Ross Bray, Xuewei Cui, Jonathan Wilson, Kevin Duffin, Zvonko Milicevic, Axel Haupt, Deborah A Robins

doi : 10.1210/clinem/dgaa863

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 388–396

Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide.

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Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease 

Aaron Broadwell, Arkadi Chines, Peter R Ebeling, Edward Franek, Shuang Huang, Shawna Smith, David Kendler, Osvaldo Messina, Paul D Miller

doi : 10.1210/clinem/dgaa851

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 397–409

The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown.

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Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study

Stephanie Than, Chris Moran, Richard Beare, Amanda J Vincent, Taya A Collyer, Wei Wang, Michele L Callisaya, Russell Thomson, Thanh G Phan, Alex Fornito, Velandai K Srikanth

doi : 10.1210/clinem/dgaa847

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 410–420

Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife.

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Reproductive Hormones and Anthropometry: A Follow-Up of PCOS and Controls From Perimenopause to Older Than 80 Years

Maria Forslund, Johanna Schmidt, Mats Br?nnstr?m, Kerstin Landin-Wilhelmsen, Eva Dahlgren

doi : 10.1210/clinem/dgaa840

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 421–430

There is a lack of knowledge about hormonal and anthropometric changes in women with polycystic ovary syndrome (PCOS) after the menopause.

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Clinical Characteristics of Short-Stature Patients With an NPR2 Mutation and the Therapeutic Response to rhGH

Xiaoan Ke, Hanting Liang, Hui Miao, Hongbo Yang, Linjie Wang, Fengying Gong, Hui Pan, Huijuan Zhu

doi : 10.1210/clinem/dgaa842

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 431–441

The natriuretic peptide receptor 2 gene (NPR2) is a causative gene of idiopathic short stature (ISS) with an incidence rate of 2% to 6%. The clinical characteristics of patients with NPR2 heterozygous mutations are atypical, and data on the efficacy of recombinant human growth hormone (rhGH) treatment in patients with NPR2 mutations are limited.

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Male Fertility Before and After Androgen Abuse

Josefine Windfeld-Mathiasen, Kim Peder Dalhoff, Jon Tr?rup Andersen, Marc Klemp, Anna Horwitz, Henrik Horwitz

doi : 10.1210/clinem/dgaa837

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 442–449

Previous research has found that male users of androgens are diagnosed approximately twice as often with infertility. We therefore set out to investigate the fertility in men using androgens.

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Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Nicole Stantonyonge, Frederic Sampedro, Jorge Méndez, Saül Mart?nez-Horta, Ana Chico, Beatriz G?mez-Anson

doi : 10.1210/clinem/dgaa832

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 450–458

Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI).

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Germline DLST Variants Promote Epigenetic Modifications in Pheochromocytoma-Paraganglioma

Alexandre Buffet, Juan Zhang, Heggert Rebel, Eleonora P M Corssmit, Jeroen C Jansen, Erik F Hensen, Judith V M G Bovée, Aurélien Morini, Anne-Paule Gimenez-Roqueplo, Frederik J Hes, Peter Devilee, Judith Favier, Jean-Pierre Bayley

doi : 10.1210/clinem/dgaa819

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 459–471

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors in which altered central metabolism appears to be a major driver of tumorigenesis, and many PPGL genes encode proteins involved in the tricarboxylic acid (TCA) cycle.

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Short Dietary Intervention with Olive Oil Increases Brown Adipose Tissue Activity in Lean but not Overweight Subjects

Milena Monfort-Pires, Mueez U-Din, Guilherme A Nogueira, Juliana de Almeida-Faria, Davi Sidarta-Oliveira, Marcella Ramos Sant’Ana, José C De Lima-J?nior, Dennys E Cintra, Heraldo Possolo de Souza, Sandra R G Ferreira, Marcelo Tatit Sapienza, Kirsi A Virtanen, Licio A Velloso

doi : 10.1210/clinem/dgaa824

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 472–484

The brown adipose tissue (BAT) is a potential target for the treatment of obesity and metabolic disorders. Its activation by cold exposure or adrenergic drugs can increase systemic insulin sensitivity and improve lipid metabolism; however, little is known about the effects of specific dietary components on BAT activity.

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Platelet Activation In Situ in Breasts at High Risk of Cancer: Relationship with Mammographic Density and Estradiol

Sofija Mijic, Charlotta Dabrosin

doi : 10.1210/clinem/dgaa820

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 485–500

High mammographic density in postmenopausal women is an independent risk factor for breast cancer by undetermined mechanisms. No preventive therapy for this risk group is available. Activated platelets release growth factors that modulate the microenvironment into a protumorigenic state. Estrogens may affect the risk of breast cancer and platelet function. Whether platelets are activated in situ in breast cancer or in normal breast tissue at high risk of breast cancer and the association to estradiol remains elusive.

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Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg) 

Dag Hofs?, Thor Olav Wider?e Hillestad, Erling Halvorsen, Farhat Fatima, Line Kristin Johnson, Morten Lindberg, Marius Svanevik, Rune Sandbu, J?ran Hjelmes?th

doi : 10.1210/clinem/dgaa808

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 501–511

Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health.

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Predictors of Vertebral Deformity in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia: The PETALE Study

Melissa Fiscaletti, Mariia Samoilenko, Josée Dubois, Marie-Claude Miron, Geneviève Lefebvre, Maja Krajinovic, Caroline Laverdière, Daniel Sinnett, Nathalie Alos

doi : 10.1210/clinem/dgaa806

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 512–525

The prevalence of vertebral deformities in long-term survivors of childhood acute lymphoblastic leukemia (ALL) is unknown. Our objectives were to identify the prevalence of vertebral deformities and their risk factors among long-term childhood ALL survivors.

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TRIM65 Promotes Invasion of Endometrial Stromal Cells by Activating ERK1/2/C-myc Signaling via Ubiquitination of DUSP6

Ying-Ting Wu, Si-Yu Ma, Wen-Qin Sun, Wei-Wei Shen, Hui-Ting Zhu, Qin Zhang, Hui-Fen Chen

doi : 10.1210/clinem/dgaa804

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 526–538

Endometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM.

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Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series 

Ferdy S van Geest, Marcel E Meima, Kyra E Stuurman, Nicole I Wolf, Marjo S van der Knaap, Cl?udia F Lorea, Fabiano O Poswar, Filippo Vairo, Nicola Brunetti-Pierri, Gerarda Cappuccio, Priyanka Bakhtiani, Sonja A de Munnik, Robin P Peeters, W Edward Visser, Stefan Groeneweg

doi : 10.1210/clinem/dgaa795

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 539–553

Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes.

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Antidiabetic Treatment, Level of Glycemic Control, and Risk of Fracture in Type 2 Diabetes: a Nested, Case-Control Study

Sarah Charlier, Janina Vavanikunnel, Claudia Becker, Susan S Jick, Christian Meier, Christoph R Meier

doi : 10.1210/clinem/dgaa796

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 554–566

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of low-trauma fractures. However, the effect of antidiabetic medication in relation to glycemic control on the risk of fracture is poorly understood.

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Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan 

Rasmus Juul Kildemoes, Michael H?jby Rasmussen, Henrik Agers?, Rune Viig Overgaard

doi : 10.1210/clinem/dgaa775

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 567–576

Somapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration.

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Improvement in Symptoms and Health-Related Quality of Life in Acromegaly Patients: A Systematic Review and Meta-Analysis 

Leonie H A Broersen, Amir H Zamanipoor Najafabadi, Alberto M Pereira, Olaf M Dekkers, Wouter R van Furth, Nienke R Biermasz

doi : 10.1210/clinem/dgaa868

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 577–587

Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.

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Recurrence Rate of Sporadic Pheochromocytomas After Curative Adrenalectomy: A Systematic Review and Meta-analysis

Isabelle Holscher, Tijs J van den Berg, Koen M A Dreijerink, Anton F Engelsman, Els J M Nieveen van Dijkum

doi : 10.1210/clinem/dgaa794

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 588–597

Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American Association of Clinical Endocrinologists and Endocrine Surgeons, and the Endocrine Society are ambiguous about the appropriate duration of follow-up. The aim of this systematic review and meta-analysis is to evaluate the recurrence rate of sporadic pheochromocytomas after curative adrenalectomy.

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Ectopic ACTH- and/or CRH-Producing Pheochromocytomas

Patrick F Elliott, Thomas Berhane, Oskar Ragnarsson, Henrik Falhammar

doi : 10.1210/clinem/dgaa488

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages 598–608

The characteristics of catecholamine-secreting pheochromocytomas have been well studied. However, less is known about the characteristics, management and outcome in patients with ectopic adrenocorticotropic hormone (ACTH) and/or corticotrophin-releasing hormone (CRH)-secreting pheochromocytomas.

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Hypothalamitis: A Novel Autoimmune Endocrine Disease. A Literature Review and Case Report 

U?ur Türe, Annamaria De Bellis, Mehmet Volkan Harput, Giuseppe Bellastella, Melih Topcuoglu, Cumhur Kaan Yaltirik, Paolo Cirillo, Rima Nur Yola, Ayd?n Sav, Fahrettin Kelestimur

doi : 10.1210/clinem/dgaa771

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e415–e429

The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic–pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate.

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Polycystic Ovary Syndrome and Brain: An Update on Structural and Functional Studies

Basak Ozgen Saydam, Bulent Okan Yildiz

doi : 10.1210/clinem/dgaa843

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e430–e441

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women in reproductive age and is associated with reproductive, endocrine, metabolic, cardiovascular, and psychological outcomes. All these disorders are thought to be affected by central mechanisms which could be a major contributor in pathogenesis of PCOS.

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Male infertility due to testicular disorders

Aditi Sharma, Suks Minhas, Waljit S Dhillo, Channa N Jayasena

doi : 10.1210/clinem/dgaa781

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e442–e459

Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.

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Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism

Maya E Lee, Yashira M Ortega-Sustache, Sunita K Agarwal, Aisha Tepede, James Welch, Adel Mandl, Rashika Bansal, Amit Tirosh, Paolo Piaggi, Craig Cochran, William F Simonds, Lee S Weinstein, Jenny E Blau

doi : 10.1210/clinem/dgaa501

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e460–e468

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and adenocorticotropic hormone-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have an increased risk of venous thromboembolism (VTE).

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Influence of Obesity in the miRNome: miR-4454, a Key Regulator of Insulin Response Via Splicing Modulation in Prostate

Vicente Herrero-Aguayo, Juan M Jiménez-Vacas, Prudencio S?ez-Mart?nez, Enrique G?mez-G?mez, Juan L L?pez-C?novas, Lourdes Garrido-S?nchez, Aura D Herrera-Mart?nez, Laura Garc?a-Bermejo, Manuel Mac?as-Gonz?lez, José L?pez-Miranda, Justo P Casta?o, Manuel D Gahete, Ra?l M Luque

doi : 10.1210/clinem/dgaa580

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e469–e484

Obesity is a major health problem associated with severe comorbidities, including type 2 diabetes and cancer, wherein microRNAs (miRNAs) might be useful as diagnostic/prognostic tools or therapeutic targets.

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Hypercalcemia in Children Using the Ketogenic Diet: A Multicenter Study

Colin P Hawkes, Sani M Roy, Bassem Dekelbab, Britney Frazier, Monica Grover, Jaime Haidet, James Listman, Sarianne Madsen, Marian Roan, Celia Rodd, Aviva Sopher, Peter Tebben, Michael A Levine

doi : 10.1210/clinem/dgaa759

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e485–e495

The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment.

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Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis

Tasma Harindhanavudhi, Yi Yang, James S Hodges, Timothy L Pruett, Varvara Kirchner, Gregory J Beilman, Melena D Bellin

doi : 10.1210/clinem/dgaa790

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e496–e506

Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied.

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Rapamycin Plus Vildagliptin to Recover ?-Cell Function in Long-Standing Type 1 Diabetes: A Double-Blind, Randomized Trial

Andrea Mario Bolla, Alessandra Gandolfi, Elisa Borgonovo, Andrea Laurenzi, Amelia Caretto, Chiara Molinari, Roberta Sara Catalano, Eleonora Bianconi, Paolo Monti, Valeria Sordi, Silvia Pellegrini, Vito Lampasona, Sabrina Costa, Marina Scavini, Emanuele Bosi, Lorenzo Piemonti

doi : 10.1210/clinem/dgaa791

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e507–e519

The aim of this study was to investigate whether treatment with rapamycin plus vildagliptin restores ?-cell function in patients with long-standing type 1 diabetes.

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Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease

Takara L Stanley, Lindsay T Fourman, Isabel Zheng, Colin M McClure, Meghan N Feldpausch, Martin Torriani, Kathleen E Corey, Raymond T Chung, Hang Lee, David E Kleiner, Colleen M Hadigan, Steven K Grinspoon

doi : 10.1210/clinem/dgaa792

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e520–e533

Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD).

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A Novel Mutation in the FSH Receptor (I423T) Affecting Receptor Activation and Leading to Primary Ovarian Failure

Teresa Zari??n, Julio Mayorga, Eduardo Jard?n-Valadez, Rubén Gutiérrez-Sagal, José Luis Maravillas-Montero, Nancy R Mej?a-Dom?nguez, Iv?n Mart?nez-Luis, Omar G Yacini-Torres, Ma-del-Carmen Cravioto, Eric Reiter, Alfredo Ulloa-Aguirre

doi : 10.1210/clinem/dgaa782

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e534–e550

Follicle-stimulating hormone (FSH) plays an essential role in gonadal function. Loss-of-function mutations in the follicle-stimulating hormone receptor (FSHR) are an infrequent cause of primary ovarian failure.

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Associations of Hair Cortisol Concentrations with General and Organ Fat Measures in Childhood

Florianne O L Vehmeijer, Susana Santos, Romy Gaillard, Yolanda B de Rijke, Trudy Voortman, Erica L T van den Akker, Janine F Felix, Elisabeth F C van Rossum, Vincent W V Jaddoe

doi : 10.1210/clinem/dgaa785

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e551–e561

Stress may lead to an adverse body fat distribution from childhood onwards.

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Proper mTORC1 Activity Is Required for Glucose Sensing and Early Adaptation in Human Pancreatic ? Cells

Qicheng Ni, Jiaxi Song, Yichen Wang, Jiajun Sun, Jing Xie, Jun Zhang, Guang Ning, Weiqing Wang, Qidi Wang

doi : 10.1210/clinem/dgaa786

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e562–e572

The mechanistic target of rapamycin complex I (mTORC1) is crucial for ?-cell identity and function in rodents. However, its possible relevance to the physiopathology of diabetes in humans remains unclear.

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Efficacy and Safety of Thermal Ablation for Solitary T1bN0M0 Papillary Thyroid Carcinoma: A Multicenter Study

Xiao-Jing Cao, Juan Liu, Ya-Lin Zhu, Lu Qi, Geng Liu, Hong-Ling Wang, Zhong-Hua Wang, Ying Zhou, Jun-Feng He, Jian-Qin Guo, Li-Li Shi, Mei Jian, Aini Shataer, Guo-Zhen Yan, Zhen-Long Zhao, Ying Wei, Li-Li Peng, Yan Li, Ying Che, Shu-Rong Wang, Ming-An Yu

doi : 10.1210/clinem/dgaa776

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e573–e581

Ultrasound-guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 papillary thyroid carcinoma (PTC) who are ineligible for or unwilling to undergo surgery.

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Serum Spermidine as a Novel Potential Predictor for Fragility Fractures

Sung Hye Kong, Jung Hee Kim, Chan Soo Shin

doi : 10.1210/clinem/dgaa745

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e582–e591

Metabolomics is an emerging tool that provides insights into the dynamics of phenotypic changes. It is a potential method for the discovery of novel serum markers of fracture.

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Circulating sDPP-4 is Increased in Obesity and Insulin Resistance but Is Not Related to Systemic Metabolic Inflammation

Nathalie Rohmann, Kristina Schlicht, Corinna Geisler, Tim Hollstein, Carina Knappe, Laura Krause, Stefanie Hagen, Alexia Beckmann, Anna Katharina Seoudy, Perdita Wietzke-Braun, Katharina Hartmann, Dominik Schulte, Kathrin Türk, Jan Beckmann, Witigo von Sch?nfels, Franziska Anna H?gele, Anja Bosy-Westphal, Andre Franke, Stefan Schreiber, Matthias Laudes

doi : 10.1210/clinem/dgaa758

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e592–e601

Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. It exists in a membrane-bound form and a soluble form (sDPP-4). Initial human studies suggested sDPP-4 to be an adipokine involved in metabolic inflammation. However, recent mechanistic data in genetically modified mice has questioned these findings.

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Radiological Thoracic Vertebral Fractures are Highly Prevalent in COVID-19 and Predict Disease Outcomes 

Luigi di Filippo, Anna Maria Formenti, Mauro Doga, Erika Pedone, Patrizia Rovere-Querini, Andrea Giustina

doi : 10.1210/clinem/dgaa738

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e602–e614

COVID-19 has become the most relevant medical issue globally. Despite several studies that have investigated clinical characteristics of COVID-19 patients, no data have been reported on the prevalence of vertebral fractures (VFs). Since VFs may influence cardiorespiratory function and disease outcomes, the aim of this study was to assess VFs prevalence and clinical impact in COVID-19.

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Biochemical Remission after Cabergoline Withdrawal in Hyperprolactinemic Patients with Visible Remnant Pituitary Adenoma

Kyungwon Kim, Yae Won Park, Daham Kim, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Cheol Ryong Ku

doi : 10.1210/clinem/dgaa744

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e615–e624

Dopamine agonists (DAs) are the first-line therapy for prolactinomas. Although pituitary tumors often do not completely disappear, discontinuing DAs in patients with no visible tumor on magnetic resonance imaging is advised.

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Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men

Bu B Yeap, Ross J Marriott, Leen Antonio, Yi X Chan, Suchitra Raj, Girish Dwivedi, Christopher M Reid, Bradley D Anawalt, Shalender Bhasin, Adrian S Dobs, Graeme J Hankey, Alvin M Matsumoto, Paul E Norman, Terence W O’Neill, Claes Ohlsson, Eric S Orwoll, Dirk Vanderschueren, Gary A Wittert, Frederick C W Wu, Kevin Murray

doi : 10.1210/clinem/dgaa743

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e625–e637

Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.

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Metabolomics of Lean/Overweight Insulin-Resistant Females Reveals Alterations in Steroids and Fatty Acids

Ilhame Diboun, Layla Al-Mansoori, Hend Al-Jaber, Omar Albagha, Mohamed A Elrayess

doi : 10.1210/clinem/dgaa732

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e638–e649

The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR.

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Angiotensin-Converting Enzyme Inhibitors Reduce Uterine Fibroid Incidence in Hypertensive Women

Nicole M Fischer, Tim O Nieuwenhuis, Bhuchitra Singh, Gayane Yenokyan, James H Segars

doi : 10.1210/clinem/dgaa718

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e650–e659

In vitro and in vivo evidence has supported the role of angiotensin II blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association.

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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C 

Félixe Pelletier, Stefanie Perrier, Ferdy K Cayami, Amytice Mirchi, Stephan Saikali, Luan T Tran, Nicole Ulrick, Kether Guerrero, Emmanouil Rampakakis, Rosalina M L van Spaendonk, Sakkubai Naidu, Daniela Pohl, William T Gibson, Michelle Demos, Cyril Goizet, Ingrid Tejera-Martin, Ana Potic, Brent L Fogel, Bernard Brais, Michel Sylvain, Guillaume Sébire, Charles Marques Lourenço, Joshua L Bonkowsky, Coriene Catsman-Berrevoets, Pedro S Pinto, Sandya Tirupathi, Petter Str?mme, Ton de Grauw, Dorota Gieruszczak-Bialek, Ingeborg Kr?geloh-Mann, Hanna Mierzewska, Heike Philippi, Julia Rankin, Tahir Atik, Brenda Banwell, William S Benko, Astrid Blaschek, Annette Bley, Eugen Boltshauser, Drago Bratkovic, Klara Brozova, Ic?ar Cimas, Christopher Clough, Bernard Corenblum, Argirios Dinopoulos, Gail Dolan, Flavio Faletra, Raymond Fernandez, Janice Fletcher, Maria Eugenia Garcia Garcia, Paolo Gasparini, Janina Gburek-Augustat, Dolores Gonzalez Moron, Aline Hamati, Inga Harting, Christoph Hertzberg, Alan Hill, Grace M Hobson, A Micheil Innes, Marcelo Kauffman, Susan M Kirwin, Gerhard Kluger, Petra Kolditz, Urania Kotzaeridou, Roberta La Piana, Eriskay Liston, William McClintock, Meriel McEntagart, Fiona McKenzie, Serge Melançon, Anjum Misbahuddin, Mohnish Suri, Fernando I Monton, Sebastien Moutton, Raymond P J Murphy, Miriam Nickel, Hüseyin Onay, Simona Orcesi, Ferda ?zk?nay, Steffi Patzer, Helio Pedro, Sandra Pekic, Mercedes Pineda Marfa, Amy Pizzino, Barbara Plecko, Bwee Tien Poll-The, Vera Popovic, Dietz Rating, Marie-France Rioux, Norberto Rodriguez Espinosa, Anne Ronan, John R Ostergaard, Elsa Rossignol, Rocio Sanchez-Carpintero, Anna Schossig, Nesrin Senbil, Laura K S?nderberg Roos, Cathy A Stevens, Matthis Synofzik, L?szl? Sztriha, Daniel Tibussek, Dagmar Timmann, Davide Tonduti, Bart P van de Warrenburg, Maria V?zquez-L?pez, Sunita Venkateswaran, Pontus Wasling, Evangline Wassmer, Richard I Webster, Gert Wiegand, Grace Yoon, Joost Rotteveel, Raphael Schiffmann, Marjo S van der Knaap, Adeline Vanderver, Gabriel ? Martos-Mreno, Constantin Polychronakos, Nicole I Wolf, Geneviève Bernard

doi : 10.1210/clinem/dgaa700

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e660–e674

4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date.

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11C-Metomidate PET/CT Detected Multiple Ectopic Adrenal Rest Tumors in a Woman With Congenital Adrenal Hyperplasia

Pia Burman, Henrik Falhammar, Erik Waldenstr?m, Anders Sundin, Ulrika Bitzén

doi : 10.1210/clinem/dgaa870

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e675–e679

Women with congenital adrenal hyperplasia (CAH) may present with androgen excess that is difficult to control with conventional suppressive doses of glucocorticoids. Clinical management is challenging, and the woman is at great risk of developing steroid-induced complications.

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Salt-Losing 21-Hydroxylase Deficiency Caused by Double Homozygosity for Two “Mild” Mutations

Jacob Ilany, Jiayan Liu, Christoph Welsch, Haike Reznik-Wolf, Ephrat Levy-Lahad, Richard J Auchus

doi : 10.1210/clinem/dgaa875

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e680–e686

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presents with different severities that correlate with the genotype. The salt-losing phenotype requires 2 alleles with “severe” mutations.

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Sarcopenia Is Associated With Reduced Function on Admission to Rehabilitation in Patients With Diabetes

Irina Churilov, Leonid Churilov, Kim Brock, David Murphy, Richard J MacIsaac, Elif I Ekinci

doi : 10.1210/clinem/dgaa878

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e687–e695

This work aims to estimate the prevalence of sarcopenia and to investigate the association between sarcopenia and functional performance in patients with and without diabetes admitted for inpatient rehabilitation.

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Clinical, Cellular, and Molecular Evidence of the Additive Antitumor Effects of Biguanides and Statins in Prostate Cancer

Juan M Jiménez-Vacas, Vicente Herrero-Aguayo, Antonio J Montero-Hidalgo, Prudencio S?ez-Mart?nez, Enrique G?mez-G?mez, Antonio J Le?n-Gonz?lez, Antonio C Fuentes-Fayos, Elena M Yubero-Serrano, Mar?a J Requena-Tapia, Miguel L?pez, Justo P Casta?o, Manuel D Gahete, Ra?l M Luque

doi : 10.1210/clinem/dgaa877

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e696–e710

Prostate cancer (PCa) is one of the leading causes of cancer-related death among the male population worldwide. Unfortunately, current medical treatments fail to prevent PCa progression in a high percentage of cases; therefore, new therapeutic tools to tackle PCa are urgently needed. Biguanides and statins have emerged as antitumor agents for several endocrine-related cancers.

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Incidence of Cabergoline-Associated Valvulopathy in Primary Care Patients With Prolactinoma Using Hard Cardiac Endpoints

Craig Edward Stiles, Guy Lloyd, Sanjeev Bhattacharyya, Richard Paul Steeds, Kambiz Boomla, Jonathan Paul Bestwick, William Martyn Drake

doi : 10.1210/clinem/dgaa882

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e711–e720

Controversy exists as to whether low-dose cabergoline is associated with clinically significant valvulopathy. Few studies examine hard cardiac endpoint data, most relying on echocardiographic findings.

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Description of the Follicular Fluid Cytokine and Hormone Profiles in Human Physiological Natural Cycles 

Marie-Pierre Piccinni, Rossella Vicenti, Federica Logiodice, Raffaella Fabbri, Ornela Kullolli, Marco Pallecchi, Roberto Paradisi, Giovanna Danza, Maria Macciocca, Letizia Lombardelli, Renato Seracchioli

doi : 10.1210/clinem/dgaa880

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e721–e738

Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles.

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Early Detection of Abnormal Growth Associated with Juvenile Acquired Hypothyroidism

Antti Saari, Jari Pokka, Outi M?kitie, Marja-Terttu Saha, Leo Dunkel, Ulla Sankilampi

doi : 10.1210/clinem/dgaa869

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e739–e748

Development of the typical growth phenotype in juvenile acquired hypothyroidism (JHT), the faltering linear growth with increasing weight, has not been thoroughly characterized.

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Proteinuria in Severe Hypothyroidism: A Prospective Study

Vijay Singh Gondil, Aarthi Chandrasekaran, Ashu Rastogi, Ashok Kumar Yadav, Ashwani Sood, Raja Ramachandran, Vivek Kumar, Manish Rathi, Harbir Singh Kohli, Vivekanand Jha, Krishan Lal Gupta

doi : 10.1210/clinem/dgaa871

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e749–e756

Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown.

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Severity of Proteinuria Is Directly Associated With Risk of Hypothyroidism in Adults

Norra Kwong, Marco Medici, Ellen Marqusee, Ari J Wassner

doi : 10.1210/clinem/dgaa872

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e757–e762

Proteinuria can cause or exacerbate hypothyroidism, possibly due to urinary loss of protein-bound thyroid hormone. However, the precise relationship between proteinuria and hypothyroidism remains unclear.

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Osteoporosis and the Risk of Parkinson’s Disease: A Nationwide, Propensity Score–Matched, Longitudinal Follow-up Study

Shih-Hao Feng, Ya-Ping Huang, Kuo-Cheng Yeh, Shin-Liang Pan

doi : 10.1210/clinem/dgaa864

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e763–e771

Osteoporosis and Parkinson’s disease (PD) often co-occur, and even patients with early-stage PD may have reduced bone-mineral density levels. This may imply that osteoporosis is associated with a higher risk of PD.

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Impact of Lean Body Mass and Insulin Sensitivity on the IGF-1–Bone Mass Axis in Adolescence: the EPICOM Study

Rikke Beck Jensen, Birgitte Bytoft, Zuzana Lohse, Sine Knorr Johnsen, Morten Frost Nielsen, Peter Sandor Oturai, Kurt H?jlund, Peter Damm, Tine D Clausen, Dorte M Jensen

doi : 10.1210/clinem/dgaa861

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e772–e781

Insulin-like growth factor-1 (IGF-1) is involved in the growth of muscle and bone mass and contributes to glucose homeostasis. The offspring of mothers with diabetes during pregnancy have an increased risk of insulin resistance (IR).

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Sustained Breast Development and Breast Anthropometric Changes in 3 Years of Gender-Affirming Hormone Treatment

Christel J M de Blok, Benthe A M Dijkman, Chantal M Wiepjes, Annemieke S Staphorsius, Floyd W Timmermans, Jan Maerten Smit, Koen M A Dreijerink, Martin den Heijer

doi : 10.1210/clinem/dgaa841

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e782–e790

Breast development is important for most trans women. An important limitation of current breast development measurement methods is that these do not allow for 3D volume analyses.

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Interrupting Prolonged Sitting Reduces Postprandial Glucose Concentration in Young Men With Central Obesity

Waris Wongpipit, Xiaoyuan Zhang, Masashi Miyashita, Stephen Heung-Sang Wong

doi : 10.1210/clinem/dgaa834

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e791–e802

Prolonged sitting elevates postprandial metabolic markers, resulting in increased risks of cardiovascular diseases and type 2 diabetes. Interrupting prolonged sitting may reduce these risks. However, more information is needed to understand the patterns of interrupting prolonged sitting to obtain metabolic health benefits.

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Thyroid Function Before, During, and After COVID-19 

Bernard Khoo, Tricia Tan, Sophie A Clarke, Edouard G Mills, Bijal Patel, Manish Modi, Maria Phylactou, Pei Chia Eng, Layla Thurston, Emma C Alexander, Karim Meeran, Alexander N Comninos, Ali Abbara, Waljit S Dhillo

doi : 10.1210/clinem/dgaa830

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e803–e811

The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported.

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Relationship of Weight Change Patterns From Young to Middle Adulthood With Incident Cardiovascular Diseases

Mengyi Liu, Zhuxian Zhang, Chun Zhou, Panpan He, Yuanyuan Zhang, Huan Li, Qinqin Li, Chengzhang Liu, Binyan Wang, Jianping Li, Yan Zhang, Xin Xu, Xiaobin Wang, Xiping Xu, Yong Huo, Fan Fan Hou, Xianhui Qin

doi : 10.1210/clinem/dgaa823

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e812–e823

The effect of weight change patterns on cardiovascular diseases (CVD) remains uncertain.

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Surgical Outcomes Among Primary Aldosteronism Patients Without Visible Adrenal Lesions

Davis Sam, Gregory A Kline, Benny So, Janice L Pasieka, Adrian Harvey, Alex Chin, Stefan J Przybojewski, Alexander A Leung

doi : 10.1210/clinem/dgaa821

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e824–e835

Many patients with unilateral primary aldosteronism (PA) have normal adrenal imaging, but little is known about their outcome following adrenalectomy.

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Women with Mild Fasting Hyperglycemia in Early Pregnancy Have More Neonatal Intensive Care Admissions

Katrien Benhalima, Paul Van Crombrugge, Carolien Moyson, Johan Verhaeghe, Sofie Vandeginste, Hilde Verlaenen, Chris Vercammen, Toon Maes, Els Dufraimont, Christophe De Block, Yves Jacquemyn, Farah Mekahli, Katrien De Clippel, Annick Van Den Bruel, Anne Loccufier, Annouschka Laenen, Caro Minschart, Roland Devlieger, Chantal Mathieu

doi : 10.1210/clinem/dgaa831

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e836–e854

To determine impact of mild fasting hyperglycemia in early pregnancy (fasting plasma glucose [FPG] 5.1-5.5 mmol/L) on pregnancy outcomes.

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Role of Age at Diagnosis in Defining Potential Familial Nonmedullary Thyroid Cancer in Kindreds With Two Affected Members

Marco Capezzone, Alfonso Sagnella, Tania Pilli, Fabio Maino, Raffaella Forleo, Silvia Cantara, Alessandra Cartocci, Maria Grazia Castagna

doi : 10.1210/clinem/dgaa798

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e855–e865

The definition of familial nonmedullary thyroid cancer (FNMTC) in 2 or more first-degree relatives is controversial due to the high probability of observing a sporadic association when only 2 members of first-degree relatives are affected.

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Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism

Tazuru Fukumoto, Hironobu Umakoshi, Masatoshi Ogata, Maki Yokomoto-Umakoshi, Yayoi Matsuda, Misato Motoya, Hiromi Nagata, Yui Nakano, Norifusa Iwahashi, Hiroki Kaneko, Norio Wada, Takashi Miyazawa, Ryuichi Sakamoto, Yoshihiro Ogawa

doi : 10.1210/clinem/dgaa812

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e866–e874

Current clinical guidelines recommend confirmation of a positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results.

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Placental Inositol Reduced in Gestational Diabetes as Glucose Alters Inositol Transporters and IMPA1 Enzyme Expression

Reshma A Pillai, Mohammed O Islam, Preben Selvam, Neha Sharma, Anne H Y Chu, Oliver C Watkins, Keith M Godfrey, Rohan M Lewis, Shiao Y Chan

doi : 10.1210/clinem/dgaa814

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e875–e890

Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood.

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Diabetes, Brain Infarcts, Cognition, and Small Vessels in the Canadian Alliance for Healthy Hearts and Minds Study

Hertzel C Gerstein, Eric E Smith, Chinthanie Ramasundarahettige, Dipika Desai, Philip Awadalla, Philippe Broet, Sandra Black, Trevor J B Dummer, Jason Hicks, Alan Moody, Jean-Claude Tardif, Koon K Teo, Jennifer Vena, Salim Yusuf, Douglas S Lee, Matthias G Friedrich, Sonia S Anand

doi : 10.1210/clinem/dgaa815

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e891–e898

Diabetes is a risk factor for cerebrovascular disease and cognitive impairment. The anatomical basis for this is uncertain.

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Effects of a Tailored Exercise Intervention in Acutely Hospitalized Oldest Old Diabetic Adults: An Ancillary Analysis

Nicol?s Mart?nez-Velilla, Pedro L Valenzuela, Mikel L S?ez de Asteasu, Fabricio Zambom-Ferraresi, Robinson Ram?rez-Vélez, Antonio Garc?a-Hermoso, Julian Librero-L?pez, Javier Gorricho, Federico Esparza Pérez, Alejandro Lucia, Mikel Izquierdo

doi : 10.1210/clinem/dgaa809

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e899–e906

To analyze the effects of a tailored exercise intervention in acutely hospitalized elderly diabetic patients.

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Multiple Endocrine Deficiencies are Common in Hypoparathyroidism–Retardation–Dysmorphism Syndrome

Odeya David, Galia Barash, Rotem Agur, Neta Loewenthal, Lior Carmon, David Shaki, Dganit Walker, Rosa Novoa, Alon Haim, Eli Hershkovitz

doi : 10.1210/clinem/dgaa807

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e907–e916

The rare hypoparathyroidism—retardation—dysmorphism (HRD) syndrome (OMIM #241410) is caused by the mutated tubulin chaperone E (TBCE) gene. This gene encodes a critical protein in the microtubule assembly pathway.

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EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas

Odelia Cooper, Vivien S Bonert, Jeremy Rudnick, Barry D Pressman, Janet Lo, Roberto Salvatori, Kevin C J Yuen, Maria Fleseriu, Shlomo Melmed

doi : 10.1210/clinem/dgaa805

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e917–e925

Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior.

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Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19 

David Tak Wai Lui, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Carol Ho Yi Fong, Chun Yiu Law, Eunice Ka Hong Leung, Kelvin Kai Wang To, Kathryn Choon Beng Tan, Yu Cho Woo, Ching Wan Lam, Ivan Fan Ngai Hung, Karen Siu Ling Lam

doi : 10.1210/clinem/dgaa813

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e926–e935

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2–related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers.

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COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study 

Grenye O’Malley, Osagie Ebekozien, Marisa Desimone, Catherina T Pinnaro, Alissa Roberts, Sarit Polsky, Nudrat Noor, Grazia Aleppo, Marina Basina, Michael Tansey, Devin Steenkamp, Francesco Vendrame, Ilona Lorincz, Priyanka Mathias, Shivani Agarwal, Lauren Golden, Irl B Hirsch, Carol J Levy

doi : 10.1210/clinem/dgaa825

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e936–e942

Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes.

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Brown Fat–Activating Lipokine 12,13-diHOME in Human Milk Is Associated With Infant Adiposity

Danielle Wolfs, Matthew D Lynes, Yu-Hua Tseng, Stephanie Pierce, Valerie Bussberg, Abena Darkwah, Vladimir Tolstikov, Niven R Narain, Michael C Rudolph, Michael A Kiebish, Ellen W Demerath, David A Fields, Elvira Isganaitis

doi : 10.1210/clinem/dgaa799

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e943–e956

Little is known about the specific breastmilk components responsible for protective effects on infant obesity. Whether 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxidized linoleic acid metabolite and activator of brown fat metabolism, is present in human milk, or linked to infant adiposity, is unknown.

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Reproductive and Perinatal Outcomes in Women with Congenital Adrenal Hyperplasia: A Population-based Cohort Study 

Angelica Lindén Hirschberg, Sebastian Gidl?f, Henrik Falhammar, Louise Frisén, Catarina Almqvist, Agneta Nordenskj?ld, Anna Nordenstr?m

doi : 10.1210/clinem/dgaa801

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e957–e965

Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women.

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Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment

Christoffer A Hagemann, Chen Zhang, Henrik H Hansen, Tina Jorsal, Kristoffer T G Rigbolt, Martin R Madsen, Natasha C Bergmann, Sebastian M N Heimbürger, Mechthilde Falkenhahn, Stefan Theis, Kristin Breitschopf, Stephanie Holm, Morten A Hedegaard, Mikkel B Christensen, Tina Vilsb?ll, Birgitte Holst, Niels Vrang, Jacob Jelsing, Filip K Knop

doi : 10.1210/clinem/dgaa803

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e966–e981

The mechanisms underlying Roux-en-Y gastric bypass (RYGB) surgery-induced weight loss and the immediate postoperative beneficial metabolic effects associated with the operation remain uncertain. Enteroendocrine cell (EEC) secretory function has been proposed as a key factor in the marked metabolic benefits from RYGB surgery.

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Elevated Circulating Glutamate Is Associated With Subclinical Atherosclerosis Independently of Established Risk Markers: A Cross-Sectional Study

Angela Lehn-Stefan, Andreas Peter, Jürgen Machann, Fritz Schick, Elko Randrianarisoa, Martin Heni, Robert Wagner, Andreas L Birkenfeld, Andreas Fritsche, Hans-Ulrich H?ring, Harald Staiger, Norbert Stefan

doi : 10.1210/clinem/dgaa898

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e982–e989

Elevated plasma glutamate levels are associated with an increased risk of cardiovascular disease (CVD). Because plasma glutamate levels are also strongly associated with visceral adiposity, nonalcoholic fatty liver disease, insulin resistance, and high circulating levels of branched-chain amino acids (BCAAs), it is unknown to what extent elevated circulating glutamate is an independent marker of an increased risk of atherosclerosis.

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Total, Bioavailable, and Free 25(OH)D Relationship with Indices of Bone Health in Elderly: A Randomized Controlled Trial

Malak El Sabeh, Paola Ghanem, Laila Al-Shaar, Maya Rahme, Rafic Baddoura, Georges Halaby, Ravinder J Singh, Dirk Vanderschueren, Roger Bouillon, Ghada El-Hajj Fuleihan

doi : 10.1210/clinem/dgaa780

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e990–e1001

Questions regarding the superiority of free and bioavailable 25-hydroxyvitamin D [25(OH)D] in predicting health outcomes remain unresolved.

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Beyond Premature Ovarian Insufficiency: Staging Reproductive Aging in Adolescent and Young Adult Cancer Survivors

Alexa C O Medica, Brian W Whitcomb, Ksenya Shliakhsitsava, Andrew C Dietz, Kelsey Pinson, Christina Lam, Sally A D Romero, Patrick Sluss, Mary D Sammel, H Irene Su

doi : 10.1210/clinem/dgaa797

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1002–e1013

Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors).

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The Management of Neuroendocrine Tumors of the Lung in MEN1: Results From the Dutch MEN1 Study Group

Medard F M van den Broek, Joanne M de Laat, Rachel S van Leeuwaarde, Annenienke C van de Ven, Wouter W de Herder, Olaf M Dekkers, Madeleine L Drent, Michiel N Kerstens, Peter H Bisschop, Bas Havekes, Wenzel M Hackeng, Lodewijk A A Brosens, Menno R Vriens, Wieneke A Buikhuisen, Gerlof D Valk

doi : 10.1210/clinem/dgaa800

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1014–e1027

Multiple endocrine neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent, with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging.

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Commentary on “Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men”

Ali Abbara, Maria Phylactou, Waljit S Dhillo

doi : 10.1210/clinem/dgaa783

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1028–e1030

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Does Kisspeptin Regulate Food Intake in Humans? An Important Journey of Discovery Has Begun

Andy V Babwah

doi : 10.1210/clinem/dgaa846

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1031–e1033

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Detection of Breast Tissue at Puberty: Is an Ultrasound Examination Necessary?

Alan D Rogol

doi : 10.1210/clinem/dgaa844

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1034–e1035

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Dual HDAC and PI3K Inhibitor: A Novel Potential Therapeutic Option in Cushing Disease

S T Sharma

doi : 10.1210/clinem/dgaa845

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1036–e1038

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Uterine Fibroids and Hypertension: Steps Toward Understanding the Link

Elizabeth A Stewart, Bijan J Borah

doi : 10.1210/clinem/dgaa829

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1039–e1041

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Commentary: Evidence-based Medicine for SIAD

Joseph G Verbalis

doi : 10.1210/clinem/dgaa826

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1042–e1043

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Birth Cohorts in Type 1 Diabetes: Preparing for the Payoff

Kristina Cossen, Andrew Muir

doi : 10.1210/clinem/dgaa736

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1044–e1045

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In Search of the Holy Grail for Growth: A Real-time Biomarker

Michele Gortakowski, Charlotte M Boney

doi : 10.1210/clinem/dgaa811

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1046–e1047

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Earlier Detection of GDM Via OGTT: Is It Helpful?

Amy Valent, David A Price

doi : 10.1210/clinem/dgaa810

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1048–e1049

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Timing Is Everything, Right? Meal Impact on Circadian Related Health 

Steven K Malin

doi : 10.1210/clinem/dgaa533

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1050–e1051

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New Horizons in Microbiota and Metabolic Health Research

Sidharth P Mishra, Shalini Jain, Subhash Taraphder, Hariom Yadav

doi : 10.1210/clinem/dgaa769

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1052–e1059

Decade-old studies have demonstrated that microbes living in our gut (microbiota) contribute to both maintaining normal metabolic function and to the pathology of metabolic diseases, such as obesity and diabetes. Emerging evidence suggests that gut microbiota influences the personalized effects of diets and drugs and impact the gut–brain axis and leaky gut inflammation to control metabolic function/diseases. Gut microbiota can be an ideal source of prognostic markers and therapies for metabolic diseases. Here we discuss the emerging concepts in the area of microbiota and metabolic interactions in personalized nutrition, drug response, and disease prognosis.

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Letter to the Editor from Neinstein and Masharani: “Approach to the Patient with Thyrotoxicosis Using Telemedicine”

Aaron B Neinstein, Umesh Masharani

doi : 10.1210/clinem/dgaa723

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1060–e1061

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Letter to the Editor from Napierska and Schettler: “Unwitting Accomplices: Endocrine Disruptors Confounding Clinical Care”

Dorota Napierska, Ted Schettler

doi : 10.1210/clinem/dgaa713

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1062–e1063

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Letter to the Editor from Knobler and Toledano: “Validation of the Swedish Diabetes Regrouping Scheme in Adult-Onset Diabetes in China”

Hilla Knobler, Yoel Toledano

doi : 10.1210/clinem/dgaa827

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1064–e1065

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Response to Letter to the Editor: “Unwitting Accomplices: Endocrine Disruptors Confounding Clinical Care”

Matthew Genco, Lisa Anderson-Shaw, Robert M Sargis

doi : 10.1210/clinem/dgaa714

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1066–e1067

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Response to Letter to the Editor from Knobler et al: “Validation of the Swedish Diabetes Regrouping Scheme in Adult-Onset Diabetes in China”

Xia Li, Shuting Yang, Xilin Yang, Zhiguang Zhou

doi : 10.1210/clinem/dgaa828

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Pages e1068–e1069

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Corrigendum to: “Trophoblast H2S Maintains Early Pregnancy via Regulating Maternal-Fetal Interface Immune Hemostasis” 

doi : 10.1210/clinem/dgaa802

The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 2, February 2021, Page e1070

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