This Week in Endocrinology — May 28, 2026

Welcome to This Week in Endocrinology. This week we're covering 6 notable papers spanning two broad themes: first, advancing equity in diabetes screening and technology, and second, rethinking our understanding of key endocrine axes from reproduction to aging. Let's dive in.

We begin in diabetes care, with a strong focus on closing persistent gaps in outcomes. A review in *Nature Reviews Endocrinology* argues that to improve outcomes for minoritized populations, we must move beyond interventions focused on changing individual behavior [1]. The authors call for a shift towards addressing the root structural and social inequities that drive disparities. This includes system-level changes in public health approaches, the healthcare workforce, quality standards, and access to care.

Building on this theme of equity, a paper in *Diabetologia* presents a powerful new tool to reduce disparities in genetic screening for type 1 diabetes [2]. Current polygenic risk scores, or PRSs, are based largely on European data and perform poorly in other ancestries. This study aimed to develop a score with comparable performance across different populations.

The Study

Investigators developed a trans-ancestry polygenic risk score, or TA-PS, for type 1 diabetes.

Methods

They used the PRS-CSx method on large genome-wide association study datasets from European, East Asian, African American, and Hispanic populations, involving over 29,000 individuals. They then validated the new score in four independent cohorts.

Results

In a multi-ancestry validation cohort, the new TA-PS showed significantly better performance, with an area under the curve of 0.89, compared to 0.85 for the older, European-based score. Crucially, the new score provided much more consistent sensitivity across ancestries. For example, at a 90th percentile risk cutoff, sensitivity was 0.71 in Europeans and 0.77 in South Asians. In contrast, the older score had sensitivities as low as 0.32 in African Americans.

Conclusions

This new trans-ancestry PRS provides comparable type 1 diabetes risk prediction in various ancestries, supporting its use for more equitable population-wide screening programs.

Rounding out our diabetes section, a new joint position statement from the European Association for the Study of Diabetes and the American Diabetes Association, published in *Diabetologia*, addresses the use of diabetes technology [3]. The statement emphasizes that while technology is transforming diabetes management, access is not uniform. It urges healthcare professionals to support individuals in accessing the right technology based on personal needs, capabilities, and preferences. A key message is the importance of challenging preconceived barriers—such as age, socioeconomic status, or comorbidities—which can often be overcome with education and support, thereby minimizing the 'digital divide'.

Next, we turn to three papers that challenge and refine our understanding of fundamental endocrine pathways, starting with a basic science discovery in reproductive endocrinology published in *Science* [4].

The Finding

Researchers have identified a key role for hypothalamic microglia in controlling the hypothalamic-pituitary-gonadal, or HPG, axis. Specifically, a signaling pathway involving RANK—the receptor activator of nuclear factor kappa B—in these immune cells is essential for normal gonadotropin-releasing hormone, or GnRH, neuron function.

Implications

In mouse models, disrupting this RANK signaling led to hypogonadotropic hypogonadism. Connecting this to human disease, the investigators also identified rare gene variants of human RANK in patients with congenital hypogonadotropic hypogonadism. This work uncovers microglia as a novel and critical regulator of GnRH neuronal function, with direct implications for understanding reproductive maturation and fertility.

From the reproductive axis to the thyroid axis, a massive study in *The Lancet Diabetes & Endocrinology* provides new insights into how thyroid function changes with age and what those changes mean for mortality [5].

The Study

This was an individual participant data analysis, pooling data from 31 prospective cohort studies and including over 137,000 adults.

Results

Longitudinal analysis showed that TSH levels tend to increase with age for everyone, regardless of regional iodine status. From age 18 to 100, the average TSH increased by about 0.6 mIU per liter in women and 1.0 mIU per liter in men from iodine-sufficient regions. While most individuals had relatively stable thyroid function over time, there was greater variability in adults over 65.

The Bottom Line

Here is the most critical finding. Compared with people whose thyroid function remained stable, *any* pattern of significant change over time was associated with increased all-cause mortality. For example, having an increasing TSH combined with an increasing free T4 was associated with nearly two and a half times the risk of death. An increasing TSH with a stable or decreasing free T4 was associated with an 80% increased risk. This suggests that instability of the thyroid axis itself, not just the absolute TSH value at a single point in time, is a powerful prognostic marker in aging.

Finally, a review in *Endocrine Reviews* examines the future of diagnosing primary aldosteronism [6]. The paper underscores that primary aldosteronism, or PA, is a major public health issue, affecting more than one in ten people with hypertension and conferring significantly higher cardiovascular risk.

The Problem

Current diagnostic methods are challenging. Screening with plasma aldosterone and renin is hampered by variability and medication interference. The gold-standard test to distinguish unilateral from bilateral disease, adrenal vein sampling, is invasive, technically demanding, and often yields inconclusive results.

The Future

The review highlights promising new biomarker research. Novel approaches using steroid profiling, as well as circulating proteomics and metabolomics, are beginning to identify molecular fingerprints that could diagnose PA and even determine its subtype non-invasively. These multi-dimensional biomarker strategies may soon transform the diagnosis and management of this common cause of secondary hypertension.

If you only have time for one paper this week, make it the individual participant data analysis on the natural history of thyroid function, published in *The Lancet Diabetes & Endocrinology* [5]. This work, involving over 137,000 participants, provides the strongest evidence to date that our interpretation of TSH needs to account for age-related drift, and more importantly, that thyroid functional instability over time is a significant predictor of mortality.

Here are the key takeaways from this week in Endocrinology.

First, when addressing diabetes disparities, we must move beyond focusing on individual patient behavior and implement system-level changes that tackle structural inequities in care [1].

Second, a new trans-ancestry polygenic risk score for type 1 diabetes is now available that performs well across diverse populations, offering a more equitable tool for population screening [2].

Third, a joint EASD and ADA statement reminds us to individualize diabetes technology and actively challenge preconceived barriers that create a digital divide [3].

Fourth, be aware that TSH levels naturally and slowly increase with age. However, any significant change or instability in thyroid function over time—whether TSH is rising or falling—is associated with a substantial increase in all-cause mortality risk [5].

And finally, keep an eye on emerging non-invasive biomarkers for primary aldosteronism, such as steroid panels, which may soon improve our ability to diagnose and subtype this common condition without relying on adrenal vein sampling [6].

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.