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Recognition of Reviewers
doi : 10.1210/clinem/dgab068
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 609–621
New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?
Christopher Edwards
doi : 10.1210/clinem/dgaa874
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 622–635
This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5?-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19–associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.
Role of Gut Microbiota in the Skeletal Response to PTH
Roberto Pacifici
doi : 10.1210/clinem/dgaa895
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 636–645
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
Placental Corticotrophin-Releasing Hormone is a Modulator of Fetal Liver Blood Perfusion
Satoru Ikenoue, Feizal Waffarn, Masanao Ohashi, Mamoru Tanaka, Daniel L Gillen, Claudia Buss, Sonja Entringer, Pathik D Wadhwa
doi : 10.1210/clinem/dgaa908
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 646–653
Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion.
Appetite-Regulating Hormones Are Reduced After Oral Sucrose vs Glucose: Influence of Obesity, Insulin Resistance, and Sex
Alexandra G Yunker, Shan Luo, Sabrina Jones, Hilary M Dorton, Jasmin M Alves, Brendan Angelo, Alexis DeFendis, Trevor A Pickering, John R Monterosso, Kathleen A Page
doi : 10.1210/clinem/dgaa865
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 654–664
Fructose compared to glucose has adverse effects on metabolic function, but endocrine responses to oral sucrose vs glucose is not well understood.
Association of Maternal-Neonatal Steroids With Early Pregnancy Endocrine Disrupting Chemicals and Pregnancy Outcomes
Margaret Banker, Muraly Puttabyatappa, Patrick O’Day, Jaclyn M Goodrich, Angela S Kelley, Steven E Domino, Yolanda R Smith, Dana C Dolinoy, Peter X K Song, Richard J Auchus, Vasantha Padmanabhan
doi : 10.1210/clinem/dgaa909
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 665–687
Steroids play an important role in fetal development and parturition. Gestational exposures to endocrine-disrupting chemicals (EDCs) affect steroidal milieu and pregnancy outcomes, raising the possibility of steroids serving as biomarkers. Most studies have not addressed the impact of EDC mixtures, which are reflective of real life scenarios.
Effects of Thyroid Status on Regional Brain Volumes: A Diagnostic and Genetic Imaging Study in UK Biobank
Tom Chambers, Richard Anney, Peter N Taylor, Alexander Teumer, Robin P Peeters, Marco Medici, Xavier Caseras, D Aled Rees
doi : 10.1210/clinem/dgaa903
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 688–696
Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit/hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status.
Disposition of Urinary and Serum Steroid Metabolites in Response to Testosterone Administration in Healthy Women
Jona Elings Knutsson, Alexander Andersson, Lasse Vestli Baekken, Anton Pohanka, Lena Ekstr?m, Angelica Lindén Hirschberg
doi : 10.1210/clinem/dgaa904
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 697–707
Little is known about how exogenous testosterone (T) affects the steroid profile in women. More knowledge would give the antidoping community keys as to how to interpret tests and detect doping.
Do the Heterozygous Carriers of a CYP24A1 Mutation Display a Different Biochemical Phenotype Than Wild Types?
Alessandro Brancatella, Daniele Cappellani, Martin Kaufmann, Simona Borsari, Paolo Piaggi, Fulvia Baldinotti, Maria Adelaide Caligo, Glenville Jones, Claudio Marcocci, Filomena Cetani
doi : 10.1210/clinem/dgaa876
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 708–717
Human cytochrome P450 24 subfamily A member 1 (CYP24A1) loss-of-function mutations result in impaired activity of the 24-hydroxylase involved in vitamin D catabolism, thus inducing a vitamin D-dependent hypercalcemia. Homozygotes often present an overt clinical phenotype named idiopathic infantile hypercalcemia (IIH), whereas it is debated whether heterozygotes display an abnormal phenotype.
A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling
Kentaro Suda, Hidenori Fukuoka, Genzo Iguchi, Keitaro Kanie, Yasunori Fujita, Yukiko Odake, Ryusaku Matsumoto, Hironori Bando, Hiroki Ito, Michiko Takahashi, Kazuo Chihara, Hiroshi Nagai, Satoshi Narumi, Tomonobu Hasegawa, Wataru Ogawa, Yutaka Takahashi
doi : 10.1210/clinem/dgaa893
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 718–723
Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear.
Effect of Initial Treatment Choice on 2-year Quality of Life in Patients with Low-risk Papillary Thyroid Microcarcinoma
Jae Hoon Moon, Chang Hwan Ryu, Sun Wook Cho, June Young Choi, Eun-Jae Chung, Jeong Hun Hah, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Ji-hoon Kim, Min Joo Kim, Su-jin Kim, Yeo Koon Kim, Chang Yoon Lee, Eun Kyung Lee, Ji Ye Lee, Kyu Eun Lee, You Jin Lee, Yumi Lee, Hyeong Won Yu, Do Joon Park, Junsun Ryu, Young Joo Park
doi : 10.1210/clinem/dgaa889
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 724–735
The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear.
A Novel Loss of Function Melanocortin-4-Receptor Mutation (MC4R-F313Sfs*29) in Morbid Obesity
Elisabetta Trevellin, Marnie Granzotto, Cristina Host, Francesca Grisan, Diego De Stefani, Alessandro Grinzato, Konstantinos Lefkimmiatis, Claudio Pagano, Rosario Rizzuto, Roberto Vettor
doi : 10.1210/clinem/dgaa885
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 736–749
Melanocortin receptor-4 (MC4R) gene mutations are associated with early-onset severe obesity, and the identification of potential pathological variants is crucial for the clinical management of patients with obesity.
Insulin Resistance Is Central to Long-Term Reversal of Histologic Nonalcoholic Steatohepatitis After Metabolic Surgery
Maria Francesca Russo, Erminia Lembo, Andrea Mari, Giulia Angelini, Ornella Verrastro, Giuseppe Nanni, Maurizio Pompili, Marco Raffaelli, Fabio Maria Vecchio, Stefan R Bornstein, Geltrude Mingrone
doi : 10.1210/clinem/dgaa892
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 750–761
Nonalcoholic steatohepatitis (NASH) is considered the hepatic counterpart of metabolic syndrome.
Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort
Donatella Capalbo, Cristina Moracas, Marco Cappa, Antonio Balsamo, Mohamad Maghnie, Malgorzata Gabriela Wasniewska, Nella Augusta Greggio, Federico Baronio, Carla Bizzarri, Giusy Ferro, Alessandra Di Lascio, Marianna Rita Stancampiano, Sara Azzolini, Giuseppa Patti, Silvia Longhi, Mariella Valenzise, Giorgio Radetti, Corrado Betterle, Gianni Russo, Mariacarolina Salerno
doi : 10.1210/clinem/dgaa881
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 762–773
Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children.
Diabetes Remission Status During Seven-year Follow-up of the Longitudinal Assessment of Bariatric Surgery Study
Jonathan Q Purnell, Elizabeth N Dewey, Blandine Laferrère, Faith Selzer, David R Flum, James E Mitchell, Alfons Pomp, Walter J Pories, Thomas Inge, Anita Courcoulas, Bruce M Wolfe
doi : 10.1210/clinem/dgaa849
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 774–788
Few studies have examined the clinical characteristics that predict durable, long-term diabetes remission after bariatric surgery.
Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment
Claudia Campana, Francesco Cocchiara, Giuliana Corica, Federica Nista, Marica Arvigo, Jessica Amarù, Diego Criminelli Rossi, Gianluigi Zona, Diego Ferone, Federico Gatto
doi : 10.1210/clinem/dgaa859
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 789–801
Discordant growth hormone (GH) and insulin-like growth factor-1 (IGF-1) values are frequent in acromegaly.
Role of Imprinting Disorders in Short Children Born SGA and Silver-Russell Syndrome Spectrum
Tomoko Fuke, Akie Nakamura, Takanobu Inoue, Sayaka Kawashima, Kaori Isono Hara, Keiko Matsubara, Shinichiro Sano, Kazuki Yamazawa, Maki Fukami, Tsutomu Ogata, Masayo Kagami
doi : 10.1210/clinem/dgaa856
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 802–813
(Epi)genetic disorders associated with small-for-gestational-age with short stature (SGA-SS) include imprinting disorders (IDs). Silver-Russell syndrome (SRS) is a representative ID in SGA-SS and has heterogenous (epi)genetic causes.
Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone
Stéphanie Espiard, Johanna McQueen, Mark Sherlock, Oskar Ragnarsson, Ragnhildur Bergthorsdottir, Pia Burman, Per Dahlqvist, Bertil Ekman, Britt Edén Engstr?m, Stanko Skrtic, Jeanette Wahlberg, Paul M Stewart, Gudmundur Johannsson
doi : 10.1210/clinem/dgaa862
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 814–825
Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.
USP8 and TP53 Drivers are Associated with CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors
Andrew V Uzilov, Patricia Taik, Khadeen C Cheesman, Pedram Javanmard, Kai Ying, Alessia Roehnelt, Huan Wang, Marc Y Fink, Chun Yee Lau, Aye S Moe, Joaquin Villar, Joshua B Bederson, Andrew F Stewart, Michael J Donovan, Milind Mahajan, Robert Sebra, Kalmon D Post, Rong Chen, Eliza B Geer
doi : 10.1210/clinem/dgaa853
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 826–842
Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropin (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown.
Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis
Cecilie Melau, John E Nielsen, Signe Perlman, Lene Lundvall, Lea Langhoff Thuesen, Kristine Juul Hare, Mette Schou Hammerum, Hanne Frederiksen, Rod T Mitchell, Anders Juul, Anne J?rgensen
doi : 10.1210/clinem/dgaa852
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 843–857
Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail.
The Gut Microbiome in Polycystic Ovary Syndrome and Its Association with Metabolic Traits
Kreete Lüll, Riikka K Arffman, Alberto Sola-Leyva, Nerea M Molina, Oliver Aasmets, Karl-Heinz Herzig, Julio Plaza-D?az, Stephen Franks, Laure Morin-Papunen, Juha S Tapanainen, Andres Salumets, Signe Altm?e, Terhi T Piltonen, Elin Org
doi : 10.1210/clinem/dgaa848
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 858–871
Despite the gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated.
Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors
Dalvinder Mandair, Mohid S Khan, Andre Lopes, Luke Furtado O’Mahony, Leah Ensell, Helen Lowe, John A Hartley, Christos Toumpanakis, Martyn Caplin, Tim Meyer
doi : 10.1210/clinem/dgaa822
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 872–882
Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined.
Testing, Monitoring, and Treatment of Thyroid Dysfunction in Pregnancy
Sun Y Lee, Elizabeth N Pearce
doi : 10.1210/clinem/dgaa945
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 883–892
Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves’ disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves’ disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment.
Approach to Interpreting Common Laboratory Pathology Tests in Transgender Individuals
Ada S Cheung, Hui Yin Lim, Teddy Cook, Sav Zwickl, Ariel Ginger, Cherie Chiang, Jeffrey D Zajac
doi : 10.1210/clinem/dgaa546
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 893–901
As the number of transgender (trans) people (including those who are binary and/or nonbinary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin, and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation.
Metabolic Impact of Intermittent Fasting in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Interventional Studies
Emily Borgundvaag, Jessica Mak, Caroline K Kramer
doi : 10.1210/clinem/dgaa926
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 902–911
Intermittent fasting (IF) has been proposed as a weight-loss strategy with additional cardiometabolic benefits in individuals with obesity. Despite its growing popularity, the effect of IF in patients with type 2 diabetes (T2DM) remains unclear.
Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis
Giovana F Piccoli, Leonardo A Mesquita, Cinara Stein, Marina Aziz, Maira Zoldan, Nath?lia A H Degobi, Bernardo F Spiazzi, Gilberto L Lopes Junior, Verônica Colpani, Fernando Gerchman
doi : 10.1210/clinem/dgaa891
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 912–921
Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events.
Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy for Remission of Type 2 Diabetes
Marco Castellana, Filippo Procino, Elisa Biacchi, Roberta Zupo, Luisa Lampignano, Fabio Castellana, Rodolfo Sardone, Andrea Palermo, Roberto Cesareo, Pierpaolo Trimboli, Gianluigi Giannelli
doi : 10.1210/clinem/dgaa737
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages 922–933
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the bariatric procedures most commonly used for the management of obesity. Whether one or the other is associated with a higher chance of remission of type 2 diabetes (T2D) is unclear.
Update on PCOS: Consequences, Challenges, and Guiding Treatment
Kathleen M Hoeger, Anuja Dokras, Terhi Piltonen
doi : 10.1210/clinem/dgaa839
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1071–e1083
Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in women and despite this, diagnostic challenges, delayed diagnosis, and less-than-optimal treatment regimens plague the condition. The International PCOS network, consisting of geographically diverse international experts in PCOS as well as consumers, engaged in a multi-year international evidence-based guideline development process that was jointly sponsored by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM). The guideline was published in 2018 and endorsed by more than 40 international societies involved in PCOS. Translation of this evidence-based guideline to medical practice and consumer groups remains a priority. However, there remain many challenges to both understanding the diagnosis and treatment of PCOS. Evidence suggests that both clinicians and consumers are not satisfied with the timeliness of diagnosis and treatment options. This review summarizes the important findings for diagnosis and treatment from the guidelines and expands on recent developments in the literature since its publication. Special attention to diagnosis at the ends of the reproductive spectrum are discussed and remaining areas of controversy are noted. Additionally, the review highlights some of the remaining challenges in the understanding and management of PCOS to help guide clinicians and investigators in this perplexing condition.
Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome
Mirte R Caanen, Henrike E Peters, Peter M van de Ven, Anne M F M Jüttner, Joop S E Laven, Marcel H A van Hooff, Cornelis B Lambalk
doi : 10.1210/clinem/dgaa949
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1084–e1095
Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated.
Testosterone Replacement Therapy Added to Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism
Yoann Barnouin, Reina Armamento-Villareal, Alessandra Celli, Bryan Jiang, Arjun Paudyal, Vijay Nambi, Mon S Bryant, Marco Marcelli, Jose M Garcia, Clifford Qualls, Dennis T Villareal
doi : 10.1210/clinem/dgaa917
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1096–e1110
Obesity and hypogonadism additively contribute to frailty in older men; however, appropriate treatment remains controversial.
First-in-Human, Double-Blind, Randomized Controlled Trial of an Oral Dose of GnRH Antagonist TU2670 in Healthy Women
Sungpil Han, Yong-Soon Cho, Seok-Kyu Yoon, Kyoung Soo Lim, Sang-Heon Cho, JaeWoo Kim, Sangmin Choe, Jinah Jung, Jong-Lyul Ghim, SangKeun Choi, Minhee Lee, Seon Mi Kim, Hun-Taek Kim, Hyeong-Seok Lim, Jae Yoon Shim, Kyun-Seop Bae
doi : 10.1210/clinem/dgaa939
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1111–e1120
To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU2670, a novel orally active, nonpeptide gonadotropin-releasing hormone (GnRH) antagonist administered to healthy female participants.
Natural History of Thyroid Disease in Children with PTEN Hamartoma Tumor Syndrome
Jessica R Smith, Enju Liu, Alanna J Church, Elizabeth Asch, Christine E Cherella, Siddharth Srivastava, Junne Kamihara, Ari J Wassner
doi : 10.1210/clinem/dgaa944
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1121–e1130
Thyroid ultrasound screening is recommended in children with PTEN hamartoma tumor syndrome (PHTS) due to increased risk of thyroid neoplasia, but the natural history of thyroid disease in children with PHTS is unclear.
Plasma Bile Acids More Closely Align With Insulin Resistance, Visceral and Hepatic Adiposity Than Total Adiposity
Ramy H Bishay, Katherine T Tonks, Jacob George, Dorit Samocha-Bonet, Gideon Meyerowitz-Katz, Donald J Chisholm, David E James, Jerry R Greenfield
doi : 10.1210/clinem/dgaa940
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1131–e1139
The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown.
The Effects of Vitamin D Supplementation During Infancy on Growth During the First 2 Years of Life
Helena H Hauta-alus, Elisa M Holmlund-Suila, Eero Kajantie, Jenni Rosendahl, Saara M Valkama, Maria Enlund-Cerullo, Sture Andersson, Outi M?kitie
doi : 10.1210/clinem/dgaa943
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1140–e1155
The relationship between maternal and infant vitamin D and early childhood growth remains inadequately understood.
Serum FSH Is Associated With BMD, Bone Marrow Adiposity, and Body Composition in the AGES-Reykjavik Study of Older Adults
Annegreet G Veldhuis-Vlug, Gina N Woods, Sigurdur Sigurdsson, Susan K Ewing, Phuong T Le, Trisha F Hue, Eric Vittinghoff, Kaipin Xu, Vilmundur Gudnason, Gunnar Sigurdsson, Deborah M Kado, Gudny Eiriksdottir, Tamara Harris, Anne L Schafer, Xiaojuan Li, Mone Zaidi, Clifford J Rosen, Ann V Schwartz
doi : 10.1210/clinem/dgaa922
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1156–e1169
Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass.
Repeat Adrenal Vein Sampling in Aldosteronism: Reproducibility and Interpretation of Persistently Discordant Results
Gregory A Kline, Alexander Ah-Chi Leung, Davis Sam, Alex Chin, Benny So
doi : 10.1210/clinem/dgaa930
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1170–e1178
The reproducibility of adrenal vein sampling (AVS) is unknown.
MorbiNet Study: Hypothyroidism Comorbidity Networks in the Adult General Population
Ferran Moratalla-Navarro, Victor Moreno, Flora L?pez-Simarro, Alba Aguado
doi : 10.1210/clinem/dgaa927
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1179–e1190
Multimorbidity impacts quality of life. We constructed hypothyroidism comorbidity networks to identify positive and negative associations with other prevalent diseases.
Early Prediction of Gestational Diabetes Mellitus in the Chinese Population via Advanced Machine Learning
Yan-Ting Wu, Chen-Jie Zhang, Ben Willem Mol, Andrew Kawai, Cheng Li, Lei Chen, Yu Wang, Jian-Zhong Sheng, Jian-Xia Fan, Yi Shi, He-Feng Huang
doi : 10.1210/clinem/dgaa899
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1191–e1205
Accurate methods for early gestational diabetes mellitus (GDM) (during the first trimester of pregnancy) prediction in Chinese and other populations are lacking.
Effects of Obesity and Insulin on Tissue-Specific Recycling Between Cortisol and Cortisone in Men
Anna J Anderson, Ruth Andrew, Natalie Z M Homer, Katherine A Hughes, Luke D Boyle, Mark Nixon, Fredrik Karpe, Roland H Stimson, Brian R Walker
doi : 10.1210/clinem/dgaa896
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1206–e1220
11?-Hydroxysteroid dehydrogenase 1 (11?HSD1) reduces inert cortisone into active cortisol but also catalyzes reverse dehydrogenase activity. Drivers of cortisol/cortisone equilibrium are unclear. With obesity, 11?HSD1 transcripts are more abundant in adipose, but the consequences for oxidation vs reduction remain unknown.
Relationship of TSH Levels with Cardiometabolic Risk Factors in US Youth and Reference Percentiles for Thyroid Function
Xinlei Chen, Shuliang Deng, Cecilia Sena, Chuhan Zhou, Vidhu V Thaker
doi : 10.1210/clinem/dgaa900
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1221–e1230
Thyroid hormones play an important role in metabolic homeostasis, and higher levels have been associated with cardiometabolic risk.
Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings
Jolanda C Naafs, Jan Pieter Marchal, Eric Fliers, Paul H Verkerk, Michiel A J Luijten, Anita Boelen, A S Paul van Trotsenburg, Nitash Zwaveling-Soonawala
doi : 10.1210/clinem/dgaa901
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1231–e1239
Early treatment of primary congenital hypothyroidism (CH) prevents irreversible brain damage. Contrary to primary CH, outcome studies on central CH are scarce. Most patients with central CH have multiple pituitary hormone deficiencies (MPHD); these patients are also at risk for neonatal hypoglycemia.
Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing
Catherine Y Zhu, Ines Donangelo, Deepashree Gupta, Dalena T Nguyen, Joana E Ochoa, Michael W Yeh, Masha J Livhits
doi : 10.1210/clinem/dgaa887
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1240–e1247
Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited.
The Effects of Ivacaftor on Bone Density and Microarchitecture in Children and Adults with Cystic Fibrosis
Melissa S Putman, Logan B Greenblatt, Michael Bruce, Taisha Joseph, Hang Lee, Gregory Sawicki, Ahmet Uluer, Leonard Sicilian, Isabel Neuringer, Catherine M Gordon, Mary L Bouxsein, Joel S Finkelstein
doi : 10.1210/clinem/dgaa890
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1248–e1261
Cystic fibrosis (CF) transmembrane conductance (CFTR) dysfunction may play a role in CF-related bone disease (CFBD). Ivacaftor is a CFTR potentiator effective in improving pulmonary and nutritional outcomes in patients with the G551D-CFTR mutation. The effects of ivacaftor on bone health are unknown.
Aldosterone Induces Vasoconstriction in Individuals with Type 2 Diabetes: Effect of Acute Antioxidant Administration
Stine H?yer Finsen, Mie Rytz Hansen, Pernille B L?rkegaard Hansen, Stefan P Mortensen
doi : 10.1210/clinem/dgaa867
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1262–e1270
Individuals with type 2 diabetes have an increased risk of endothelial dysfunction and cardiovascular disease. Plasma aldosterone could contribute by reactive oxygen species–dependent mechanisms by inducing a shift in the balance between a vasoconstrictor and vasodilator response to aldosterone.
New Anti-Müllerian Hormone Target Genes Involved in Granulosa Cell Survival in Women With Polycystic Ovary Syndrome
Chrystèle Racine, Carine Genêt, Camille Bourgneuf, Charlotte Dupont, Florence Plisson-Petit, Julien Sarry, Christelle Hennequet-Antier, Corinne Vigouroux, Emmanuelle Mathieu d’Argent, Alice Pierre, Danielle Monniaux, Stéphane Fabre, Nathalie di Clemente
doi : 10.1210/clinem/dgaa879
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1271–e1289
A protective effect of anti-Müllerian hormone (AMH) on follicle atresia was recently demonstrated using long-term treatments, but this effect has never been supported by mechanistic studies. This work aimed to gain an insight into the mechanism of action of AMH on follicle atresia and on how this could account for the increased follicle pool observed in women with polycystic ovary syndrome (PCOS).
Efficacy of Sex Steroid Therapy Without Progestin or GnRH Agonist for Gonadal Suppression in Adult Transgender Patients
India I Pappas, Wendy Y Craig, Lindsey V Spratt, Daniel I Spratt
doi : 10.1210/clinem/dgaa884
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1290–e1300
Testosterone (T) or estradiol (E2) are administered to suppress gonadal function in female-to-male (FTM) and male-to-female (MTF) transgender patients. How often sex steroids cause adequate suppression without GnRH agonist (GnRHa) or progestin therapy has not been reported.
Screening of a Large Cohort of Asymptomatic SDHx Mutation Carriers in Routine Practice
Clotilde Saie, Alexandre Buffet, Juliette Abeillon, Delphine Drui, Sophie Leboulleux, Jérôme Bertherat, Delphine Zenaty, Caroline Storey, Françoise Borson-Chazot, Nelly Burnichon, Marie Vincent, Judith Favier, Eric Baudin, Sophie Giraud, Anne-Paule Gimenez-Roqueplo, Laurence Amar, Charlotte Lussey-Lepoutre
doi : 10.1210/clinem/dgaa888
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1301–e1315
When an SDHx mutation is identified in a patient with a pheochromocytoma (PCC) or a paraganglioma (PGL), predictive genetic testing can detect mutation carriers that would benefit from screening protocols.
The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery
Skand Shekhar, Raven McGlotten, Sunyoung Auh, Kristina I Rother, Lynnette K Nieman
doi : 10.1210/clinem/dgaa858
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1316–e1331
We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing syndrome (CS).
10-Year Comparative Follow-up of Familial versus Multifactorial Chylomicronemia Syndromes
Manon Belhassen, Eric Van Ganse, Maeva Nolin, Marjorie Bérard, Hanane Bada, Eric Bruckert, Michel Krempf, Vinciane Rebours, René Valero, Philippe Moulin
doi : 10.1210/clinem/dgaa838
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1332–e1342
The relative incidence of acute pancreatitis, ischemic cardiovascular disease, and diabetes in hyperchylomicronemic patients exhibiting familial chylomicronemia syndrome (FCS) or multifactorial chylomicronemia syndrome (MCS) is unknown.
Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection
José L Hern?ndez, Daniel Nan, Marta Fernandez-Ayala, Mayte Garc?a-Unzueta, Miguel A Hern?ndez-Hern?ndez, Marcos L?pez-Hoyos, Pedro Mu?oz-Cacho, José M Olmos, Manuel Gutiérrez-Cuadra, Juan J Ruiz-Cubill?n, Javier Crespo, V?ctor M Mart?nez-Taboada
doi : 10.1210/clinem/dgaa733
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1343–e1353
The role of vitamin D status in COVID-19 patients is a matter of debate.
Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center
Giulia Carosi, Valentina Morelli, Giulia Del Sindaco, Andreea Liliana Serban, Arianna Cremaschi, Sofia Frigerio, Giulia Rodari, Eriselda Profka, Rita Indirli, Roberta Mungari, Veronica Resi, Emanuela Orsi, Emanuele Ferrante, Alessia Dolci, Claudia Giavoli, Maura Arosio, Giovanna Mantovani
doi : 10.1210/clinem/dgaa793
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1354–e1361
Coronavirus disease 2019 (COVID-19) represents a global health emergency, and infected patients with chronic diseases often present with a severe impairment. Adrenal insufficiency (AI) is supposed to be associated with an increased infection risk, which could trigger an adrenal crisis.
Epidemiology and Comorbidity of Adrenal Cushing Syndrome: A Nationwide Cohort Study
Chang Ho Ahn, Jung Hee Kim, Man Young Park, Sang Wan Kim
doi : 10.1210/clinem/dgaa752
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1362–e1372
Adrenal Cushing syndrome (CS) is a major subtype of CS and has a high surgical cure rate. However, only a few studies have investigated the epidemiology and long-term outcomes of adrenal CS.
Time-of-day and Meal Size Effects on Clinical Lipid Markers
Leilah K Grant, Charles A Czeisler, Steven W Lockley, Shadab A Rahman
doi : 10.1210/clinem/dgaa739
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1373–e1379
Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology.
Factors Associated With the Decline of C-Peptide in a Cohort of Young Children Diagnosed With Type 1 Diabetes
Andrea K Steck, Xiang Liu, Jeffrey P Krischer, Michael J Haller, Riitta Veijola, Markus Lundgren, Simi Ahmed, Beena Akolkar, Jorma Toppari, William A Hagopian, Marian J Rewers, Helena Elding Larsson
doi : 10.1210/clinem/dgaa715
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021
Understanding factors involved in the rate of C-peptide decline is needed to tailor therapies for type 1 diabetes (T1D).
Effects of Intermittent Fasting or Calorie Restriction on Markers of Lipid Metabolism in Human Skeletal Muscle
Bo Liu, Amy T Hutchison, Campbell H Thompson, Kylie Lange, Gary A Wittert, Leonie K Heilbronn
doi : 10.1210/clinem/dgaa707
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1389–e1399
Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR).
Adrenal Venous Sampling–Guided Adrenalectomy Rates in Primary Aldosteronism: Results of an International Cohort (AVSTAT)
Youichi Ohno, Mitsuhide Naruse, Felix Beuschlein, Florentine Schreiner, Mirko Parasiliti-Caprino, Jaap Deinum, William M Drake, Francesco Fallo, Carmina T Fuss, Marianne A Grytaas, Takamasa Ichijo, Nobuya Inagaki, Miki Kakutani, Darko Kastelan, Ivana Kraljevic, Takuyuki Katabami, Tomaz Kocjan, Silvia Monticone, Paolo Mulatero, Sam O’Toole, Hiroki Kobayashi, Masakatsu Sone, Mika Tsuiki, Norio Wada, Tracy Ann Williams, Martin Reincke, Akiyo Tanabe
doi : 10.1210/clinem/dgaa706
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1400–e140
Adrenal venous sampling (AVS) is the current criterion standard lateralization technique in primary aldosteronism (PA). Japanese registry data found that 30% of patients with unilateral PA did not undergo adrenalectomy, but the reasons for this and whether the same pattern is seen internationally are unknown.
Determinants of Self-reported Health Outcomes in Adrenal Insufficiency: A Multisite Survey Study
Dingfeng Li, Natalia Genere, Emma Behnken, Majlinda Xhikola, Tiffany Abbondanza, Anand Vaidya, Irina Bancos
doi : 10.1210/clinem/dgaa668
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1408–e1419
Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes.
Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study
Tao Tao, Yi Zhang, Yu-Chen Zhu, Jia-Rong Fu, Yu-Ying Wang, Jie Cai, Jing-Yu Ma, Yu Xu, Yi-Ning Gao, Yun Sun, WuQiang Fan, Wei Liu
doi : 10.1210/clinem/dgaa692
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1420–e1432
Up to 40% of patients with polycystic ovary syndrome (PCOS) have prediabetes; an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established.
A Prospective Study of Children Aged 0–8 Years with CAH and Adrenal Insufficiency Treated with Hydrocortisone Granules
Uta Neumann, Katarina Braune, Martin J Whitaker, Susanna Wiegand, Heiko Krude, John Porter, Dena Digweed, Bernard Voet, Richard J M Ross, Oliver Blankenstein
doi : 10.1210/clinem/dgaa626
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1433–e1440
Children with congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI) require daily hydrocortisone replacement with accurate dosing.
Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea
Angela Delaney, Adam B Burkholder, Christopher A Lavender, Lacey Plummer, Veronica Mericq, Paulina M Merino, Richard Quinton, Katie L Lewis, Brooke N Meader, Alessandro Albano, Natalie D Shaw, Corrine K Welt, Kathryn A Martin, Stephanie B Seminara, Leslie G Biesecker, Joan E Bailey-Wilson, Janet E Hall
doi : 10.1210/clinem/dgaa609
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1441–e1452
Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility.
An Opportunity to Better Assess Breast Development in Transgender Women
John Henry Pang, Joshua D Safer
doi : 10.1210/clinem/dgaa934
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1453–e1454
A LEAP2 Forward in Gut-Induced Metabolic Profiling
Steven K Malin
doi : 10.1210/clinem/dgaa929
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1455–e1457
Further Evidence that Breast Milk Lipids Control Adiposity
Tam?s R?szer
doi : 10.1210/clinem/dgaa910
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1458–e1459
Targeting Soluble DPP-4 for Insulin Resistance: Origin Matters
Lale Ozcan, Devram S Ghorpade, Ira Tabas
doi : 10.1210/clinem/dgaa902
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1460–e1462
Redefining Congenital Hypothyroidism?
Guy Van Vliet, Patricia Diaz Escagedo
doi : 10.1210/clinem/dgaa905
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1463–e1465
MTOR and Beta Cell Adaptation in T2D
Alberto Bartolomé, Utpal B Pajvani
doi : 10.1210/clinem/dgaa906
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1466–e1467
Intermittent Fasting and Muscle Lipid Metabolism: Commentary on: Liu et al “Effects of intermittent fasting or calorie restriction on markers of lipid metabolism in human skeletal muscle”
Kelsey Gabel, Krista A Varady
doi : 10.1210/clinem/dgaa818
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1468–e1470
Risk Stratification in Pediatric Thyroid Cancer: Growing Evidence for Individualized Therapy
Ari J Wassner
doi : 10.1210/clinem/dgaa705
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1471–e1472
Does Genetic Susceptibility of the Gonadotropic Axis Explain the Variable Impact of Stressors Causing Functional Hypothalamic Amenorrhea?
Jacques Young, MD, PhD
doi : 10.1210/clinem/dgaa677
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1473–e1475
Androgens and Heart Failure: New Observations Illuminating an Aging Conundrum
Bu B Yeap, Girish Dwivedi
doi : 10.1210/clinem/dgaa676
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1476–e1478
Which reference range should we use for transgender and gender diverse patients?
Michael S Irwig
doi : 10.1210/clinem/dgaa671
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1479–e1480
New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms
Tamar Tchkonia, Allyson K Palmer, James L Kirkland
doi : 10.1210/clinem/dgaa728
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1481–e1487
The elderly population is increasing faster than other segments of the population throughout the world. Age is the leading predictor for most chronic diseases and disorders, multimorbidity, geriatric syndromes, and impaired ability to recover from accidents or illnesses. Enhancing the duration of health and independence, termed healthspan, would be more desirable than extending lifespan merely by prolonging the period of morbidity toward the end of life. The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.
New Horizons: Circadian Control of Metabolism Offers Novel Insight Into the Cause and Treatment of Metabolic Diseases
Shaunak Deota, Satchidananda Panda
doi : 10.1210/clinem/dgaa691
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1488–e1493
Metabolic homeostasis is achieved by endocrine factors, signaling cascades, and metabolic pathways that sense and respond to metabolic demands in different organs. However, the recent discovery that almost every component of this regulatory system is also modulated by circadian rhythm highlights novel etiology and prognosis of metabolic diseases. First, chronic circadian rhythm disruption, as in shiftwork or shiftwork-like lifestyle, can increase the risk for metabolic diseases. Second, by understanding factors that affect circadian rhythm, we can implement new behavioral or pharmacological interventions for the prevention and management of metabolic disorders. One of these novel circadian-based interventions is time-restricted eating (TRE) in which all daily caloric intake is restricted to a consistent window of 8 to 12 hours. In preclinical animal models, TRE can prevent or reverse many metabolic diseases. Circadian research has also catalyzed attempts to optimally time the dosing of existing drugs to treat metabolic diseases or develop new drugs that target the circadian clock to treat metabolic disorders.
Letter to the Editor From Murad: “Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis”
M Hassan Murad
doi : 10.1210/clinem/dgaa933
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Page e1494
Letter to the Editor from Murad: “The Effect of Vitamin D on Falls: A Systematic Review and Meta-Analysis”
M Hassan Murad
doi : 10.1210/clinem/dgaa928
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Page e1495
Letter to the Editor from Zhu and Rossi: “Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism”
Rui Zhu, Gian Paolo Rossi
doi : 10.1210/clinem/dgaa787
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1496–e1497
Response to Letter to the Editor from Zhu and Rossi: “Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism”
Kanran Wang, Jinbo Hu, Jun Yang, Peter J Fuller, Shumin Yang, Qifu Li
doi : 10.1210/clinem/dgaa788
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1498–e1499
Response to Letter to the Editor from Smith et al: “Osteosarcopenia in Reproductive-Aged Women With Polycystic Ovary Syndrome: A Multicenter Case-Control Study”
Maryam Kazemi, Anna E Thalacker-Mercer, Marla E Lujan
doi : 10.1210/clinem/dgaa670
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Pages e1500–e1501
Corrigendum to: “Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity”
doi : 10.1210/clinem/dgaa725
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Page e1502
Erratum to: “Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma”
doi : 10.1210/clinem/dgaa680
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 3, March 2021, Page e1503
