This Week in Endocrinology — May 21, 2026

Welcome to This Week in Endocrinology. This week we're covering 10 notable papers spanning new insights into the cellular pathogenesis of type 1 diabetes, updates in reproductive endocrinology and long-term health, and practical guidance on challenges in endocrine diagnosis and management. Let's dive in.

We begin with a deep dive into islet biology, with two papers from *Science Translational Medicine* offering a window into the cellular stress that precedes the onset of type 1 diabetes. These studies suggest that beta-cell dysfunction is established long before clinical diagnosis.

The first paper explores the role of the innate immune response in beta-cell resilience [2]. During a viral infection, the body produces cytokines like interferon-alpha. Researchers found that in response to interferon-alpha, a subset of healthy human beta-cells produces a burst of mitochondrial reactive oxygen species, or ROS. This ROS production appears to be a critical part of a healthy, acute antiviral response. However, when they examined islets from donors with type 1 diabetes, this protective ROS response was diminished. The findings suggest that an impaired ability of beta-cells to mount this adaptive stress response may contribute to their destruction during the pathogenesis of type 1 diabetes.

In a complementary study also in *Science Translational Medicine*, another group of researchers investigated autophagy, the cell's waste-recycling process, which is known to be crucial for beta-cell health [3]. Using a novel biosensor and real-time intravital microscopy in the nonobese diabetic, or NOD, mouse model, they were able to visualize autophagic flux in vivo. They discovered that defects in this essential recycling process were already present in beta-cells *before* the onset of hyperglycemia. This impairment was observed at baseline and was also seen in response to interferon-alpha, linking it to the same inflammatory stress pathways highlighted in the first paper. Together, these studies paint a picture of beta-cells under duress, with key protective mechanisms failing long before autoimmune diabetes becomes clinically apparent.

Providing broader context, a comprehensive review in *Endocrine Reviews* summarizes the central role of insulin and IGF signaling in maintaining islet cell biology [4]. Dysregulation of this pathway is a hallmark of type 2 diabetes. The review covers emerging concepts, such as the role of nuclear insulin receptors and the discovery of an insulin inhibitory receptor, highlighting the complex signaling networks required to maintain functional islet mass and glucose homeostasis.

Next, we turn to reproductive endocrinology, with findings that connect the hypothalamus, the ovaries, and the skeleton, impacting health from puberty through menopause.

A fundamental discovery published in *Science* identifies a new regulator of the hypothalamic-pituitary-gonadal, or HPG, axis [7]. Researchers found that hypothalamic microglia—the resident immune cells of the brain—are critical for normal reproductive function. Specifically, a signaling pathway known as RANK signaling within these microglia is required for proper gonadotropin-releasing hormone, or GnRH, neuron function. When this pathway was depleted in microglia in mice, the animals developed hypogonadotropic hypogonadism. Supporting the clinical relevance of this finding, the team also identified rare gene variants of the human RANK gene in patients with this condition. This uncovers microglia as key players in regulating sexual maturation and fertility.

Shifting to clinical outcomes in younger women, a study in *The Journal of Clinical Endocrinology and Metabolism* examines the combined impact of polycystic ovary syndrome and metabolic dysfunction-associated steatotic liver disease, or MASLD [9]. Following a community-based cohort of adolescent girls into adulthood, the study found that having both PCOS and MASLD during adolescence dramatically increased the risk for an adverse cardiometabolic phenotype by age 27. Compared to having either condition alone or neither, young women with both PCOS and MASLD had significantly higher insulin resistance and worse lipid profiles. Notably, PCOS without co-existing MASLD or obesity in adolescence did not predict future insulin resistance, underscoring that the combination of these conditions identifies a particularly high-risk group.

Looking at another critical life stage, early perimenopause, a separate study in *JCEM* from the Study of Women's Health Across the Nation, or SWAN, cohort identifies powerful new predictors of bone loss [10]. Researchers aimed to find markers that could predict fast, imminent bone mineral density decline over the next one to two years. They found that low levels of anti-Mullerian hormone, or AMH, a marker of ovarian reserve, and high levels of C-telopeptide, or CTX, a marker of bone resorption, were each independently associated with a greater risk of rapid bone loss. When combined, the predictive power was significantly stronger than either marker alone. For each standard deviation decrease in AMH, the risk of fast spinal bone loss increased by 45 percent, while for each standard deviation increase in CTX, the risk rose by 35 percent. This combination of markers could help clinicians identify women who would benefit most from early intervention to prevent fractures.

Our final section covers several papers from *The Journal of Clinical Endocrinology and Metabolism* and *Clinical Endocrinology* offering practical solutions to common and complex clinical challenges.

First, for patients with ACTH-dependent Cushing's syndrome, venous thromboembolism, or VTE, is a major cause of morbidity and mortality. A study in *JCEM* evaluated a protocol for routine thromboprophylaxis [8].

Methods Researchers at a single center retrospectively reviewed outcomes before and after implementing a policy of routine prophylaxis with 10 milligrams of oral rivaroxaban once daily for all patients with ACTH-dependent Cushing's.

Results In the pre-policy cohort of 29 patients, nearly 14 percent developed a VTE. In the post-policy cohort of 41 patients, rivaroxaban was initiated in 39 individuals. Notably, no VTE events occurred in any patient after starting rivaroxaban prophylaxis. The treatment was well-tolerated, with no major or minor bleeding complications observed over a median duration of nearly 8 months. This study provides strong support for the early initiation of routine VTE prophylaxis in this high-risk population.

Staying with hyperfunctional endocrine tumors, another paper in *JCEM* addresses the difficult task of localizing insulinomas, especially after conventional imaging has failed [1].

The Study In a dual-center retrospective study, investigators assessed the performance of 68-Gallium-DOTA-exendin-4 PET/CT, a form of GLP-1 receptor-targeted imaging. The primary analysis focused on 58 patients with biochemically proven hyperinsulinemic hypoglycemia whose prior conventional imaging—such as CT, MRI, or ultrasound—was negative or inconclusive.

Results The PET/CT was positive in 42 of these 58 patients, corresponding to an impressive detection rate of 72 percent. Among 32 patients with subsequent histological verification, the sensitivity of the scan was nearly 94 percent. The authors conclude that this imaging modality has a substantial clinical impact, enabling PET/CT-guided surgery in patients who would otherwise face a diagnostic and therapeutic dead end.

Moving to the pituitary, a review article in *JCEM* provides a clinically-oriented overview of the growing role of germline genetic testing for pituitary adenomas [6]. The authors emphasize that a genetic component is increasingly recognized, particularly in patients with young-onset disease, a family history, or syndromic features. The review covers the established predisposition genes, such as MEN1, AIP, and SDHx, which have defined roles in guiding surveillance and family screening. It also discusses a growing list of emerging candidate genes whose clinical relevance is still being defined. The article serves as a contemporary guide for clinicians on when to consider genetic testing and how to use the results for personalized care.

Finally, a review from *Clinical Endocrinology* highlights a dual public health challenge in the United Kingdom regarding iodine, with lessons for clinicians elsewhere [5]. The authors describe a paradox. On one hand, mild-to-moderate iodine deficiency is re-emerging, particularly among women of reproductive age, vegans, and those who avoid dairy and use unfortified plant-based milks. On the other hand, a growing minority of patients present with iodine-induced thyroid dysfunction, driven by social media trends promoting 'thyroid detoxes' and kelp-based supplements that deliver dangerously high doses. The review calls for endocrinologists to be aware of both extremes and advocates for routine dietary counseling and public health measures like salt iodization to correct this imbalance.

If you only have time for one paper this week, make it the study on rivaroxaban thromboprophylaxis in Cushing's syndrome from *The Journal of Clinical Endocrinology and Metabolism* [8]. It provides a straightforward and effective protocol to mitigate the high VTE risk in this population, addressing a critical gap in care with a readily available intervention.

Here are the key takeaways from this week in Endocrinology.

First, consider routine prophylactic rivaroxaban in patients with ACTH-dependent Cushing's syndrome to prevent VTE. This single-center experience showed it was safe and appeared highly effective.

Second, in patients with suspected insulinoma but negative conventional imaging, 68-Gallium-DOTA-exendin-4 PET/CT is a high-yield next step, with a detection rate over 70 percent that can directly guide surgical management.

Third, for your adolescent female patients, the combination of PCOS and metabolic dysfunction-associated steatotic liver disease, or MASLD, signals a much higher future cardiometabolic risk than either condition alone, warranting more aggressive risk factor management and counseling.

Fourth, in early perimenopausal women, combining a low AMH with a high CTX level can identify those at highest risk for imminent, rapid bone loss, allowing for earlier counseling and potential intervention.

And finally, be aware of the dual iodine problem. Screen for deficiency in at-risk groups like pregnant women and vegans, while actively cautioning all patients against high-dose iodine supplements promoted online.

That's your roundup for This Week in Endocrinology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.