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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 IV, the editor-in-chief of The Journal of Clinical Endocrinology & Metabolism gives us his picks for this year’s top discoveries.
Editor-in-Chief of JCEM, Paul M. Stewart, MD, FRCP, FMedSci, executive dean and professor at the University of Leeds School of Medicine in the United Kingdom selected five papers from JCEM, that “highlight some of the remarkable advances that JCEM communicates across the globe — from technology-driven applications into clinical practice such as artificial intelligence and the power of genetic analysis to the understanding of disease mechanism, first-in-man investigation of novel therapeutics, and seminal clinical trials.”
“An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism,” by Takacs I., et al. published in March.
“Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci,” by Stamou M.I., et al. published in November 2023.
“Artificial Intelligence Model Assisting Thyroid Nodule Diagnosis and Management: A Multicenter Diagnostic Study,” by Ha E.J., et al. published in August.
“Increased Prevalence of Germline Pathogenic CHEK2 Variants in Individuals With Pituitary Adenomas,” by De Sousa S.M.C., et al. published in November.
“Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy ,” by Bhasin S., et al. published in July.
The Scientist Behind the Science:
“This is the first study to suggest a role for the breast cancer predisposition gene, CHEK2, in pituitary tumorigenesis, with a germline mutation yield of 3% in individuals with pituitary adenomas,” says lead author of “Increased Prevalence of Germline Pathogenic CHEK2 Variants in Individuals With Pituitary Adenomas,” Sunita M. C. De Sousa, MBBS, PhD, of the Endocrine & Metabolic Unit, Royal Adelaide Hospital; The South Australian Adult Genetics Unit, Royal Adelaide Hospital; and the Adelaide Medical School, University of Adelaide, Australia. “Beyond the possibility of CHEK2 as a new pituitary tumorigenesis gene, our work here and in a related 2023 paper suggests that relatively common, less penetrant variants in genes like CHEK2 and PAM might act as risk alleles for pituitary adenoma formation. The risk allele hypothesis might explain both the high frequency of pituitary adenomas and patchy pedigrees in affected kindreds.”
Shalender Bhasin, MB, BS: The Scientist Behind the Science:
“The TRAVERSE Trial is the largest and one of the longest randomized trials of testosterone replacement therapy (TRT) in middle-aged and older men with hypogonadism. The TRAVERSE trial’s findings have several important clinical implications,” according to lead author of Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy,” Shalender Bhasin, MB, BS, of the Research Program in Men’s Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women’s Hospital, Harvard Medical School in Boston, Mass.
“First, a majority of middle-aged and older men with hypogonadism enrolled in TRAVERSE (50.8%) reported significant depressive symptoms. So middle-aged and older men with hypogonadism should be evaluated for depressive symptoms because depression adversely affects quality of life, ability to function in daily life, and increases the risk of substance use and self-harm.
Second, the trial, by virtue of its large size and relatively long duration, provided the first high-quality evidence that TRT improves mood and energy in men with hypogonadism and low mood.
Third, over 10% of men in the trial reported major depressive disorder or had severe depressive symptoms. TRT did not improve depressive symptoms in these men with major depressive disorder. Thus, TRT does not represent an effective treatment option for most men with clinical depressive disorders.
Fourth, the trial dispelled a widely held dogma in the field that mid- or late-life onset, low-grade, persistent depressive disorder (LG-PDD, previously called dysthymia) is specifically associated with testosterone deficiency and improves with TRT. The prevalence of late life LG-PDD in the study participants was very low (about 1.5%).
The TRAVERSE trial’s findings should facilitate a more informed appraisal of the benefits and risks of testosterone treatment by middle-aged and older men with hypogonadism and their clinicians.”
The Scientist Behind the Science:
“The main takeaway for clinicians is that there are multiple genetic mechanisms driving risk of polycystic ovarian syndrome (PCOS), and these may contribute to the clinical heterogeneity that is seen in patients with this condition,” says “Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci,” corresponding author Miriam S. Udler, MD, PhD, from the Program in Medical and Population Genetics, Broad Institute in Cambridge, Mass; the Diabetes Unit, Endocrine Division, Massachusetts General Hospital in Boston, Mass.; and the Center for Genomic Medicine, Massachusetts General Hospital, in Boston, Mass. “While our findings are not yet ready for clinical application, we envision that improved understanding of the causal pathways leading to PCOS will ultimately lead to more precise diagnosis, prognosis, and treatment.”
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