Weekly Endocrinology Research Analysis
This week’s endocrinology literature highlights three high-impact advances: mechanistic neuroendocrine work revealing a POMC→paraventricular thalamus μ‑opioid microcircuit that paradoxically drives sugar appetite in sated states; a multicenter proof-of-concept showing endoscopic ultrasound–guided radiofrequency ablation (EUS‑RFA) as a safe, adrenal-sparing option for left-sided aldosterone-producing adenomas; and preclinical discovery that macrophages protect sensory axons in diabetic peripheral
Summary
This week’s endocrinology literature highlights three high-impact advances: mechanistic neuroendocrine work revealing a POMC→paraventricular thalamus μ‑opioid microcircuit that paradoxically drives sugar appetite in sated states; a multicenter proof-of-concept showing endoscopic ultrasound–guided radiofrequency ablation (EUS‑RFA) as a safe, adrenal-sparing option for left-sided aldosterone-producing adenomas; and preclinical discovery that macrophages protect sensory axons in diabetic peripheral neuropathy, opening immune-based neuroprotection strategies. Together these papers span basic mechanism, minimally invasive intervention, and translational immunology with immediate implications for obesity/feeding biology, primary aldosteronism management, and diabetic neuropathy research.
Selected Articles
1. Thalamic opioids from POMC satiety neurons switch on sugar appetite.
In mice, hypothalamic POMC satiety neurons were shown to paradoxically promote sugar appetite via projections to the paraventricular thalamus that inhibit postsynaptic neurons through mu‑opioid receptor signaling. The circuit is preferentially engaged during sugar consumption in sated states, and pharmacologic or circuit inhibition reduced intake of high‑sugar diets.
Impact: Reveals a novel, receptor-specific neurocircuit linking satiety signaling with hedonic sugar intake, providing a mechanistic basis for post-meal dessert consumption and a potential target to reduce sugar overconsumption without broadly suppressing appetite.
Clinical Implications: Translationally, thalamic μ‑opioid signaling downstream of POMC neurons could be explored as a selective therapeutic target (pharmacologic or neuromodulatory) to curb sugar overconsumption and obesity-related eating behaviors, pending safety and human validation.
Key Findings
- POMC neurons can simultaneously promote satiety and activate sugar appetite.
- A POMC→paraventricular thalamus projection inhibits postsynaptic neurons via mu‑opioid receptor signaling.
- Inhibiting this thalamic opioid circuit reduces intake of high‑sugar diets in sated mice.
2. Endoscopic, ultrasound-guided, radiofrequency ablation of aldosterone-producing adenomas (FABULAS): a UK, multicentre, prospective, proof-of-concept trial.
A UK multicentre prospective proof-of-concept trial of EUS‑guided transgastric radiofrequency ablation (EUS‑RFA) for left-sided aldosterone-producing adenomas (APAs) reported no prespecified major hazards across 35 procedures, successful targeting of PET‑CT positive nodules, biochemical complete/partial cure in 75%, and clinical hypertension cure in 43% at 6 months. The procedure offers an adrenal‑sparing, minimally invasive alternative in selected patients.
Impact: Demonstrates a feasible, image-guided, adrenal‑sparing intervention that could change management for selected APA patients unwilling/unfit for adrenalectomy or AVS, with strong safety and early efficacy signals in a high‑impact clinical journal.
Clinical Implications: In expert centers, EUS‑RFA may be offered as an adrenal‑sparing treatment option for select left-sided APAs, but randomized comparisons with adrenalectomy, extension to right‑sided lesions, and longer follow-up are required before widespread adoption.
Key Findings
- No prespecified major hazards across 35 EUS‑RFA procedures (gastric/adrenal perforation, major hemorrhage, infarction).
- All PET‑CT positive nodules were targeted with localized reduction in radiotracer uptake at 3 months.
- Biochemical complete/partial cure in 75% and clinical hypertension cure in 43% at 6 months.
3. Macrophages protect against sensory axon loss in peripheral neuropathy.
This preclinical study identifies a protective role for macrophages in preserving sensory axons in models of peripheral neuropathy relevant to type 2 diabetes and obesity. The work reframes macrophages as potential neuroprotective effectors and nominates innate immune pathways as targets to prevent axon degeneration in diabetic neuropathy.
Impact: Diabetic neuropathy currently lacks disease‑modifying therapies; demonstrating macrophage‑mediated axon protection identifies an actionable immunologic axis for therapeutic development to preserve sensory function.
Clinical Implications: Although preclinical, the findings support development of macrophage‑targeted or microenvironment‑modifying therapies and biomarker strategies to enhance axonal preservation alongside glycemic control in patients with diabetic neuropathy.
Key Findings
- Macrophages prevent or mitigate sensory axon loss in preclinical models of peripheral neuropathy.
- Findings position innate immune modulation as a strategy to preserve axons in diabetes‑related neuropathy.
- Provides mechanistic basis to identify macrophage subsets and signals for translation to therapies.