Daily Endocrinology Research Analysis
A multicentre randomized trial shows that adrenalectomy for mild autonomous cortisol secretion (MACS) significantly improves hypertension control and reduces antihypertensive medications. A UK Biobank proteomics study identifies plasma protein signatures that stratify heterogeneous risks in MASLD independent of steatosis severity, highlighting ADM, ASGR1, FABP4, and CDHR2 as mediators. A large adaptive RCT finds crisugabalin provides rapid pain relief in diabetic peripheral neuropathic pain, wit
Summary
A multicentre randomized trial shows that adrenalectomy for mild autonomous cortisol secretion (MACS) significantly improves hypertension control and reduces antihypertensive medications. A UK Biobank proteomics study identifies plasma protein signatures that stratify heterogeneous risks in MASLD independent of steatosis severity, highlighting ADM, ASGR1, FABP4, and CDHR2 as mediators. A large adaptive RCT finds crisugabalin provides rapid pain relief in diabetic peripheral neuropathic pain, with effects evident by day 2 and earlier than pregabalin.
Research Themes
- Adrenal disorders and hypertension management
- Proteomics-driven risk stratification in metabolic liver disease
- Rapid-acting analgesic therapy for diabetic neuropathic pain
Selected Articles
1. Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial.
In this multicentre RCT of hypertensive patients with MACS and unilateral adrenal incidentalomas, adrenalectomy led to a higher proportion achieving normal home blood pressure with reduced antihypertensive therapy versus conservative care (46% vs 15%; adjusted RD 0.34; p=0.0038). The surgery group required fewer and lower-intensity medications, with supportive ABPM changes and similar rates of serious adverse events.
Impact: Provides the first randomized evidence that adrenalectomy improves hypertension management in MACS, addressing a long-standing clinical controversy.
Clinical Implications: For hypertensive patients with unilateral incidentalomas and MACS, minimally invasive adrenalectomy should be actively considered to reduce medication burden and normalize BP, with structured pre/postoperative BP assessment.
Key Findings
- Primary endpoint achieved more often with adrenalectomy: 46% vs 15% with conservative care (adjusted RD 0.34; p=0.0038).
- Fewer patients required antihypertensive therapy after surgery (43% vs 96% still on treatment at study end); mean treatment step was markedly lower (−2.05).
- 24-hour ABPM improvements paralleled HBPM findings; serious adverse events were similar between groups, with three surgery-related events.
Methodological Strengths
- Randomised, multicentre design with standardized stepped-care antihypertensive protocol and rigorous HBPM/ABPM endpoints.
- Intention-to-treat analysis with stratified blocked randomisation and 13-month follow-up.
Limitations
- Open-label design may introduce performance bias.
- Modest sample size after run-in and limited to 13 months; generalizability beyond trial criteria requires caution.
Future Directions: Assess long-term cardiovascular outcomes, metabolic effects (e.g., diabetes risk), and cost-effectiveness of surgical versus medical management in MACS.
2. Proteomic variation underlies the heterogeneous risk of metabolic dysfunction-associated steatotic liver disease for subsequent chronic diseases.
In 42,508 UK Biobank participants with MASLD, a plasma proteomic signature derived from 2,911 proteins predicted higher risks of liver fibrosis, CVD, CKD, CRD, and depression (adjusted HRs 1.30–4.94). Risk stratification by the signature remained largely independent of steatosis severity and cardiometabolic factors, and mediation analyses highlighted ADM, ASGR1, FABP4 (common mediators) and CDHR2 (fibrosis-specific).
Impact: Introduces a proteome-based risk signature that explains MASLD heterogeneity across multiple organ systems and pinpoints candidate mediators and therapeutic targets.
Clinical Implications: Proteomic profiling may enhance risk stratification beyond steatosis severity, identifying MASLD patients who need intensified surveillance for fibrosis, CVD, CKD, and CRD, and informing biomarker-driven interventions targeting ADM/ASGR1/FABP4 or CDHR2 pathways.
Key Findings
- Proteomic signature associated with higher risks of liver fibrosis, CVD, CKD, CRD, and depression in MASLD (adjusted HRs 1.30–4.94).
- Risk gradients by signature persisted after adjusting for steatosis degree and cardiometabolic risk factors (except depression).
- Mediation implicated ADM, ASGR1, FABP4 as common mediators; CDHR2 was fibrosis-specific.
Methodological Strengths
- Large prospective cohort (N=42,508) with broad plasma proteomics (2,911 proteins) and multiorgan outcomes.
- Robust statistical approach including Cox models, adjusted survival curves, and mediation analyses with adjustment for steatosis and cardiometabolic factors.
Limitations
- Steatosis defined by fatty liver index, not imaging/biopsy; potential misclassification.
- Observational design limits causal inference; residual confounding possible; depression association attenuated after adjustments.
Future Directions: Validate proteomic signatures across cohorts and modalities (imaging/biopsy), test biomarker-guided surveillance strategies, and experimentally interrogate ADM/ASGR1/FABP4 and CDHR2 pathways for therapeutic targeting.
3. Rapid Onset of Pain Relief with Crisugabalin in Patients with Diabetic Peripheral Neuropathic Pain: Findings from a Multicenter, Randomized, Double-Blind, Controlled Study.
In a phase 2/3 adaptive, multicentre, double-blind RCT (n=596), crisugabalin 40 or 80 mg/day significantly reduced average daily pain versus placebo from week 1 through week 13, while pregabalin separated from placebo from week 6. NRS and sleep interference improved as early as day 2 with crisugabalin, and safety was acceptable with low serious adverse event rates.
Impact: Demonstrates rapid-onset analgesia in diabetic neuropathic pain with earlier separation from placebo than pregabalin, addressing an unmet need for faster symptom control.
Clinical Implications: Crisugabalin may be considered when rapid pain relief is prioritized in DPNP, potentially reducing early disability and sleep disruption; head-to-head effectiveness and long-term safety studies are warranted.
Key Findings
- Crisugabalin 40 and 80 mg/day reduced ADPS versus placebo from week 1 through week 13 (P<0.05), while pregabalin differences emerged from week 6.
- Secondary outcomes (NRS and daily sleep interference) improved as early as day 2 with crisugabalin.
- Safety profile was acceptable with low serious adverse event rates and no increase in dropouts.
Methodological Strengths
- Multicentre, randomized, double-blind, placebo- and active-controlled design with large sample (n=596).
- Pre-specified early time-point assessments enabling detection of onset of action; adaptive phase 2/3 framework.
Limitations
- 13-week duration limits long-term efficacy/safety inference and functional outcomes.
- Details on rescue analgesics and subgroup efficacy (e.g., by HbA1c control) were not reported in the abstract.
Future Directions: Head-to-head trials versus pregabalin/gabapentin on onset and magnitude of analgesia, evaluation of quality-of-life and function, and long-term safety in diverse DPNP populations.