Daily Endocrinology Research Analysis
Across endocrinology today, three studies advance fracture risk assessment, endocrine oncology safety, and perioperative aldosteronism care. A multi-faceted CT-based biomechanical test markedly outperforms DXA and FRAX for hip fracture prediction, ICIs double the risk of new-onset type 1 diabetes and quintuple DKA risk, and preoperative MRA in unilateral primary aldosteronism is safe and linked to superior long-term biochemical cure.
Summary
Across endocrinology today, three studies advance fracture risk assessment, endocrine oncology safety, and perioperative aldosteronism care. A multi-faceted CT-based biomechanical test markedly outperforms DXA and FRAX for hip fracture prediction, ICIs double the risk of new-onset type 1 diabetes and quintuple DKA risk, and preoperative MRA in unilateral primary aldosteronism is safe and linked to superior long-term biochemical cure.
Research Themes
- Advanced imaging-based fracture risk stratification
- Endocrine toxicities of immune checkpoint inhibitors
- Perioperative optimization in primary aldosteronism
Selected Articles
1. Improved Prediction of Hip Fracture Using Multi-Faceted Biomechanical Computed Tomography.
Using routine abdominal-pelvic CT scans, a new BCT Risk Score integrating bone, muscle, and soft tissue metrics outperformed DXA hip T-score and FRAX for predicting 5-year hip fracture. In women, c-statistic reached 0.89 and sensitivity 81.4% (vs 47.8% for DXA threshold and 75.9% for FRAX). Similar advantages were observed in men and for 2-year outcomes.
Impact: This test could leverage existing CT scans to identify high-risk patients with markedly improved sensitivity, addressing underuse and limited sensitivity of DXA. It offers an immediately scalable pathway to enhance fracture prevention.
Clinical Implications: Opportunistic BCT assessment on routine CT could be integrated into workflows to flag high-risk older adults for osteoporosis therapy and fall prevention, potentially increasing treatment rates and reducing hip fractures.
Key Findings
- In women, BCT achieved c-statistic 0.89 (95% CI 0.87-0.90) vs BMD 0.81 and FRAX 0.85 for 5-year hip fracture prediction.
- Using thresholds, sensitivity was higher for BCT (≥75: 81.4%) than BMD (T-score ≤ -2.5: 47.8%) and FRAX (hip risk ≥ 3.0%: 75.9%), with comparable PPVs (13.6% vs 15.3% vs 12.7%).
- Model inputs spanned age, femoral strength, trabecular/cortical BMD ratio, muscle area, intramuscular fat, femoral neck volume, hip width, and posterior fat thickness; performance advantages held in men and at 2 years.
Methodological Strengths
- Large healthcare system source population (n=341,364) with separate development (n=3,035) and geographically distinct validation cohort (n=2,124).
- Direct head-to-head comparison with DXA-equivalent BMD and FRAX; robust discrimination metrics and clinically actionable thresholds.
Limitations
- Retrospective design may introduce selection and confounding biases; calibration across different CT scanners/workflows may vary.
- FRAX was calculated without parental fracture history, potentially underestimating its performance.
Future Directions: Prospective implementation studies to test whether BCT-guided care increases osteoporosis treatment initiation and reduces incident hip fractures; cost-effectiveness and health equity assessments across diverse systems.
2. Immune checkpoint inhibitor therapy and risk of type 1 diabetes mellitus in metastatic cancer patients.
In a matched cohort of 50,926 metastatic cancer patients, ICIs doubled the risk of new-onset T1DM and increased DKA risk more than fivefold over a median 2-year follow-up. High-risk features included baseline HbA1c >6.0%, male sex, white race, and dual checkpoint blockade.
Impact: Quantifies rare but serious endocrine toxicities of ICIs at scale, enabling risk stratification and informing monitoring protocols across oncology and endocrinology.
Clinical Implications: Implement baseline and periodic glucose/HbA1c monitoring in ICI-treated patients, with heightened vigilance for DKA symptoms, particularly in high-risk subgroups and those on dual checkpoint blockade.
Key Findings
- After 1:1 matching (n=25,463 per group), ICIs increased T1DM risk (HR 2.35; 95% CI 1.81-3.04) and DKA risk (HR 10.58; 95% CI 4.21-26.59).
- Cumulative incidence: T1DM 0.75% vs 0.32% (RR 2.32), DKA 0.20% vs 0.04% (RR 5.00) for ICI vs non-ICI.
- High-risk subgroups included baseline HbA1c >6.0%, male sex, white race, and dual checkpoint blockade; median follow-up 764 vs 692 days.
Methodological Strengths
- Large, multi-system EHR dataset with robust 1:1 propensity score matching to balance baseline covariates.
- Consistent results across hazard ratios and cumulative incidence; subgroup analyses identify clinically actionable risk factors.
Limitations
- Outcome identification via ICD-10 codes may misclassify T1DM/DKA; lack of autoantibody or C-peptide confirmation.
- Residual confounding and channeling by indication cannot be fully excluded in observational design.
Future Directions: Develop prediction tools to identify high-risk patients pre-ICI; prospective monitoring protocols and mechanistic studies of β-cell autoimmunity under different ICI regimens.
3. Mineralocorticoid receptor antagonist pre-adrenalectomy in primary aldosteronism.
In 355 unilateral PA patients from a national registry, presurgical MRA (mostly spironolactone) did not increase immediate or short-term postoperative complications but was linked to superior long-term biochemical cure (81.7% vs 57.1%). Multivariable analysis supported an independent association.
Impact: Addresses a common, variably managed perioperative question in PA and provides safety and potential efficacy signals that could inform preoperative standardization.
Clinical Implications: Preoperative MRA can be used to optimize blood pressure and potassium control in unilateral PA prior to adrenalectomy without added postoperative risk and may improve long-term biochemical cure.
Key Findings
- Among 355 patients, 76.9% received preoperative MRA (spironolactone 64.5%, eplerenone 35.5%).
- No group differences in postoperative hyperkalemia, hypoaldosteronism, renal impairment, blood pressure changes, or short-term biochemical outcomes (≤90 days).
- Long-term complete biochemical response was higher with preoperative MRA (81.7%) vs non-pretreated (57.1%; p=0.004); MRA use independently associated with success.
Methodological Strengths
- Registry-based multicenter cohort with detailed clinical and hormonal data pre- and post-surgery.
- Multivariable analysis to adjust for baseline differences; multiple time horizons (immediate, short-term, long-term).
Limitations
- Non-randomized design with potential selection bias; MRA-pretreated patients had more severe baseline disease.
- Adrenal vein sampling guided surgery in only 33.5% overall, which may affect lateralization accuracy and outcomes.
Future Directions: Prospective trials to define optimal timing, agent, and dosing of MRA pre-adrenalectomy and to assess impacts on clinical (blood pressure remission) and biochemical outcomes.