Daily Endocrinology Research Analysis
Three standout endocrinology papers advance clinical monitoring and mechanistic understanding across adrenal and reproductive disorders. Urine steroidomics with machine learning accurately stratified treatment control in pediatric congenital adrenal hyperplasia, a clamp-based study dissected insulin dynamics driving hyperandrogenemia in PCOS, and a global ART registry documented major shifts toward cryopreservation and single embryo transfer with reduced multiple births.
Summary
Three standout endocrinology papers advance clinical monitoring and mechanistic understanding across adrenal and reproductive disorders. Urine steroidomics with machine learning accurately stratified treatment control in pediatric congenital adrenal hyperplasia, a clamp-based study dissected insulin dynamics driving hyperandrogenemia in PCOS, and a global ART registry documented major shifts toward cryopreservation and single embryo transfer with reduced multiple births.
Research Themes
- Biomarker-driven monitoring in adrenal disorders
- Insulin dynamics and androgen excess in PCOS
- Global practice trends in assisted reproduction
Selected Articles
1. Predicting treatment outcome in congenital adrenal hyperplasia using urine steroidomics and machine learning.
In a prospective pediatric CAH cohort, machine learning applied to 24-hour urine steroid profiles accurately classified treatment control (AUC 0.88 using metabolites alone; 0.90 with clinical data). Key metabolites (e.g., pregnanetriol, 17α-hydroxypregnanolone) contributed to distinguishing optimal from undertreatment. Findings support routine urine steroidomics to enhance treatment monitoring.
Impact: Introduces a robust, noninvasive, data-driven strategy to monitor CAH control beyond conventional serum markers, with immediate applicability to pediatric care pathways.
Clinical Implications: Comprehensive 24-hour urine steroid profiling with ML could standardize and improve CAH treatment monitoring, reducing under- and overtreatment and guiding dose adjustments without relying solely on serum 17-OHP.
Key Findings
- sPLS-DA using only 24 h urine metabolites classified optimal vs undertreatment with AUC 0.88; adding clinical variables increased AUC to 0.90.
- Metabolites such as pregnanetriol and 17α-hydroxypregnanolone helped exclude optimal control, while 17β-estradiol, cortisone, tetrahydroaldosterone, androstenetriol, and etiocholanolone helped exclude undertreatment.
- Undertreated patients showed more heterogeneous urine steroid profiles than optimally treated patients.
- Accurate classification was feasible even without clinical data, supporting routine urine steroidomics.
Methodological Strengths
- Prospective cohort with repeated 24-hour urine collections across two visits
- Targeted GC-MS quantification of 40 steroids with ML (sPLS-DA) and ROC analysis
Limitations
- Moderate sample size (59 patients; 112 visits) and pediatric focus may limit generalizability
- Lack of external validation and implementation outcomes; single-technology platform
Future Directions: External multi-center validation, integration into clinical workflows with decision support, and interventional studies testing steroidomics-guided dose adjustment versus standard monitoring.
2. Alterations of insulin sensitivity, clearance, and secretion, either alone or in combination, in women with PCOS: impact on metabolic profile and androgenemia.
In 355 women with PCOS, insulin resistance, reduced insulin metabolic clearance (MCRI), and increased secretion were highly prevalent and often coexisted. Each independently predicted higher free testosterone; IR and increased secretion predicted impaired glucose tolerance, while IR and low MCRI predicted metabolic syndrome. Greater numbers of insulin defects aligned with worse metabolic and androgen profiles.
Impact: Gold-standard phenotyping clarifies distinct insulin dynamics that drive hyperandrogenemia in PCOS, informing mechanism-based patient stratification and therapeutic choices.
Clinical Implications: Beyond targeting insulin resistance, clinicians should consider heterogeneity in insulin clearance and secretion when managing PCOS; tailored strategies (lifestyle, insulin-sensitizers, weight loss, potentially agents affecting hepatic insulin clearance) may better reduce androgen excess and cardiometabolic risk.
Key Findings
- Hyperinsulinemia present in 65.4%; IR in 69.6%, reduced MCRI in 57.2%, increased HOMA β in 60.0%; 87.6% had ≥1 insulin abnormality.
- M-clamp, MCRI, and HOMA β-index each independently predicted higher serum free testosterone.
- IR and increased secretion predicted altered glucose tolerance; IR and low MCRI predicted metabolic syndrome.
- Greater number of insulin abnormalities associated with progressively worse metabolic parameters and androgens.
Methodological Strengths
- Hyperinsulinemic euglycemic clamp to measure insulin sensitivity and MCRI
- High-quality androgen assays (LC/MS-MS, equilibrium dialysis) in a sizable cohort
Limitations
- Cross-sectional design limits causal inference
- Insulin secretion estimated by surrogate (HOMA β); cohort limited to Caucasian women
Future Directions: Longitudinal studies to test causal pathways and to evaluate whether therapies targeting insulin clearance versus secretion differentially improve hyperandrogenemia and metabolic risk.
3. International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2019.
Global ART activity rose in 2019 with 3.54 million cycles and 783k infants. Practice patterns shifted toward embryo cryopreservation and single embryo transfer, with frozen autologous transfers comprising 61.8% and multiple delivery rates decreasing, particularly in frozen and PGT cycles.
Impact: Provides the most comprehensive, contemporary benchmark of ART effectiveness and safety, documenting rapid adoption of cryopreservation and single embryo transfer with reduced multiple births.
Clinical Implications: Supports counseling patients toward single embryo transfer and broader use of frozen strategies and PGT when indicated, aligning with safety goals to reduce multiple gestations while maintaining delivery rates.
Key Findings
- 3,544,683 cycles reported with 783,073 infants; estimated ≥3,855,694 cycles in reporting countries including nonreporting clinics.
- Autologous frozen-thawed transfers comprised 61.8% of autologous transfers (up from 14.8% in 2015); freeze-all cycles rose to 38.4%.
- PGT cycles increased to 6.6% of reported cycles; multiple delivery rates decreased, especially in frozen cycles (13.0%) and PGT cycles (4.2%).
- Per-transfer delivery rates were similar for autologous fresh (31.3%) and frozen (31.9%) transfers; PGT transfers had 48.7%.
Methodological Strengths
- Largest contemporary global ART dataset with standardized registry reporting
- Trend analysis across multiple years enabling robust benchmarking of practice and outcomes
Limitations
- Heterogeneity in reporting across countries and possible underreporting by nonparticipating clinics
- Observational cross-sectional design precludes causal inference; variable definitions may differ by registry
Future Directions: Evaluate 2020–2021 pandemic impacts, assess cost-effectiveness of freeze-all and PGT at population scale, and refine policy for single embryo transfer to further reduce multiples.