Eureka! The Top Endocrine Discoveries of 2024 – Part V

For the tenth year running, Endocrine News talks to editors from Endocrine Society publications to unearth the most impressive breakthroughs in endocrine science and research for 2024. This year, we also talk to some of the “scientists behind the science” to get their insights on their cutting-edge research. In Part V, the editors of The Journal of Clinical Endocrinology & Metabolism Case Reports give us their picks for this year’s top discoveries.

From the Editor of JCEM Case Reports

William F. Young, Jr., MD, MSc, professor of medicine in the Mayo Clinic College of Medicine and Science in Rochester, Minn., chose three papers from JCEM Case Reports.

“Pembrolizumab-induced Thyroiditis, Hypophysitis and Adrenalitis: A Case of Triple Endocrine Dysfunction,” by Rossi S., et al. published in November. “Immunotherapy has revolutionized the field of medical oncology,” Young explains. “However, one of the unintended consequences of immune checkpoint inhibitors is autoimmune endocrinopathies. In this report, the authors present a remarkable case of multiple sequential endocrine toxicities. This case serves as a good reminder for clinicians regarding the multiple different effects on target glands and the key role for endocrinologists in sorting out complex and dynamic endocrine dysfunction.”

“Transformation of a Benign Adrenocortical Adenoma to a Metastatic Adrenocortical Carcinoma Is Rare But It Happens,” byAngelousi A., et al. published in August. Young said: “Reading this case report gave me the chills. The authors present a 64-year-old man with a 3-cm lipid rich (unenhanced CT attenuation <10 Hounsfield units) and nonfunctioning adrenal adenoma that, 13 years later, developed into a high-grade cortisol- and androgen-secreting adrenocortical carcinoma. Endocrinology is a humbling subspecialty, and we are challenged by cases that defy conventional wisdom . . .”

Reading [‘Transformation of a Benign Adrenocortical Adenoma to a Metastatic Adrenocortical Carcinoma Is Rare But It Happens‘] gave me the chills. The authors present a 64-year-old man with a 3-cm lipid rich … and nonfunctioning adrenal adenoma that, 13 years later, developed into a high-grade cortisol- and androgen-secreting adrenocortical carcinoma. Endocrinology is a humbling subspecialty, and we are challenged by cases that defy
conventional wisdom . . .” — William F. Young, Jr., Md, MSC, Editor-in-Chief, JCEM Case Reports

“Recurrent Falls Due to Hypoglycemia: Case of an IGF-2-producing Fibrous Tumor of the Pleura,” by Guijt, MC; Heineman D.J. and Jonker J.T., published in May. “I enjoy reading case reports like this one — where the broad differential diagnosis of an endocrine disorder is discussed and the authors walk through the step-by-step diagnostic assessment,” Young says. “Here, the authors discuss the broad differential diagnosis of hypoglycemia, which, based on a thorough diagnostic evaluation, leads to non–islet cell tumor hypoglycemia caused by an IGF-2–producing fibrous tumor of the pleura.”

More From the Editors of JCEM Case Reports

Associate editor Bulent Okan Yildiz, MD, professor of endocrinology and metabolism at Hacettepe University of Medicine in Ankara, Turkey, selected “Understanding the genetic complexity of puberty timing across the allele frequency spectrum,” by Kentistou K.A., et al.  from the July issue of Nature Genetics. “Early puberty is several times more common in girls than boys and we witness puberty happening at younger ages,” he explains. “This has significant implications both in the short and long term including higher risk for cardiometabolic disease and cancer. Therefore, it is highly important to explore determinants of age at menarche. The study by Kentistou et al is the largest genome-wide association study on this topic so far and identifies several genetic alterations that might trigger puberty and potentially link reproductive timing to diseases in adult life.”

Yildiz also liked Rosselot C., et al.’s “Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system” from the July issue of Science Translational Medicine: “Viable strategies on restoration of beta cell function are highly relevant for diabetes management. Commonly used antidiabetic medications are not able to increase the number of beta cells. Combining a dual tyrosine-regulated kinase 1A (DYRK1A) inhibitor with a glucagon-like peptide 1 (GLP1) receptor agonist, Rosselot et al. show a four- to seven-fold increase in beta cell mass in diabetic and non-diabetic mice in three months and reversal of diabetes. They also show beta cell mass increases through enhanced cell proliferation, function and survival. These data point to therapeutic potential of a novel combination for treatment of diabetes.”

 The Scientist Behind the Science

Corresponding author Adolfo Garcia-Ocaña, professor and chair of the Department of Molecular & Cellular Endocrinology and the Ruth B. & Robert K. Lanman Endowed Chair in Gene Regulation & Drug Discovery Research, Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Beckman Research Institute, in Duarte, Calif. says, “The most important observation of this study is that treatment with the combination of a DYRK1A inhibitor with a GLP-1R agonist (exendin-4) increases actual human beta cell mass in vivo by a mean of four- to sevenfold in diabetic and nondiabetic mice over three months and reverses diabetes, without alteration in human alpha cell mass. The treatment was safe with no tissue abnormalities detected following analysis of multiple tissues in these mice. 

We believe this is an important therapeutic observation for diabetes treatment since it could help to recover the beta cell mass lost in diabetes.  Specifically, in people with type 2 diabetes, a four- to sevenfold increase in three months would seem more than sufficient. Although type 1 diabetes provides a greater challenge because baseline beta cell mass is lower in established type 1 diabetes than in type 2 diabetes, a four- to sevenfold increase in three months should improve glycemic control and reduce ‘fragility,’ once control of autoimmunity is in place.”