Daily Endocrinology Research Analysis
Top endocrinology findings span precision risk stratification in neuroendocrine tumors, cardiometabolic outcomes in type 2 diabetes, and liver-directed benefits of SGLT2 inhibitors. A meta-analysis quantifies genotype-specific metastatic risk in pheochromocytoma/paraganglioma, a nationwide cohort underscores HFpEF as the predominant and underrecognized heart failure phenotype in T2D, and an updated RCT meta-analysis shows SGLT2 inhibitors improve steatosis and fibrosis surrogates in NAFLD.
Summary
Top endocrinology findings span precision risk stratification in neuroendocrine tumors, cardiometabolic outcomes in type 2 diabetes, and liver-directed benefits of SGLT2 inhibitors. A meta-analysis quantifies genotype-specific metastatic risk in pheochromocytoma/paraganglioma, a nationwide cohort underscores HFpEF as the predominant and underrecognized heart failure phenotype in T2D, and an updated RCT meta-analysis shows SGLT2 inhibitors improve steatosis and fibrosis surrogates in NAFLD.
Research Themes
- Genotype-informed risk stratification in endocrine oncology
- Heart failure phenotyping in type 2 diabetes
- Pharmacologic modulation of metabolic liver disease with SGLT2 inhibitors
Selected Articles
1. Metastatic disease in phaeochromocytomas and paragangliomas in various genotypes - A systematic review and meta-analysis.
This systematic review/meta-analysis quantifies time-adjusted metastatic rates in PPGL by genotype, showing substantially higher rates for several germline variants (for example, SDHA 13.73 and MAX 9.66 per 100 patient-years) versus no-variant cases (1.55 per 100 patient-years). Cluster analyses and meta-regression further highlight elevated risks in cluster 1 genes, with SDHB showing a 2.3-fold higher rate than other cluster 1 variants.
Impact: Provides genotype-specific, time-adjusted metastatic risk estimates that can directly inform surveillance intensity and patient counseling in PPGL.
Clinical Implications: Adopt genotype-tailored surveillance strategies (e.g., imaging frequency and modality) and risk communication; prioritize closer follow-up in SDHx/MAX carriers, especially SDHB/SDHA. Supports integrating genetic results into individualized care pathways.
Key Findings
- Non-variant PPGL cases had a metastatic rate of 1.55 per 100 patient-years.
- Germline variants showed higher rates: SDHA 13.73, MAX 9.66, NF1 4.11, SDHC 6.27, VHL 2.34, RET 1.91, SDHD 2.03 per 100 patient-years.
- Meta-regression indicated a 2.3-fold higher metastatic rate for SDHB compared with other cluster 1 variants; SDHB could not be pooled due to high heterogeneity.
Methodological Strengths
- Systematic search with time-adjusted outcome (per 100 patient-years)
- Genotype-stratified meta-analyses and meta-regression
Limitations
- High heterogeneity in several analyses, notably SDHB
- Reliance on observational cohorts with potential selection and surveillance biases
Future Directions: Prospective, standardized, genotype-anchored surveillance cohorts to refine absolute risks; integrate biochemical markers and imaging phenotypes to build individualized risk models.
BACKGROUND: Paragangliomas and phaeochromocytomas (PPGLs) are rare neuroendocrine tumours with 10-20% of patients developing metastatic disease. The tumours exhibit a high degree of heritability, and pathogenic genetic variants have been associated with metastases. OBJECTIVE: We aimed to investigate the association between the genotype of PPGL patients and their risk of metastatic disease, adjusting for time. METHODS: A systematic search was conducted in PubMed and Embase. The primary outcome was the rate of metastatic disease per 100 followed patient-years analysed through meta-analyses. RESULTS: A sign
2. HFpEF as the predominant and underrecognized heart failure phenotype in type 2 diabetes: evidence from the DIABET-IC study.
In a 3-year nationwide prospective cohort of 1,517 T2D patients, HFpEF was common at baseline and the predominant incident HF phenotype (46.6% of new HF). HFpEF patients were older, more often female, with obesity/hypertension. Mortality was similarly elevated in HFpEF and HFrEF; natriuretic peptides were subthreshold in >20% of HFpEF, indicating underdiagnosis. Uptake of SGLT2 inhibitors increased over time, while other guideline therapies lagged in HFpEF.
Impact: Defines the clinical profile, incidence, and management gaps of HFpEF in T2D, highlighting underdiagnosis and the need for evidence-based therapies such as SGLT2 inhibitors.
Clinical Implications: Implement systematic HF screening in T2D (including echocardiography and natriuretic peptides recognizing subthreshold levels in HFpEF) and broaden use of SGLT2 inhibitors. Tailor management to HF phenotype with proactive detection strategies for HFpEF.
Key Findings
- HFpEF accounted for 46.6% of incident HF and had similar mortality to HFrEF.
- HFpEF patients were older, more often female, with higher prevalence of obesity and hypertension.
- Over 20% of HFpEF had natriuretic peptide levels below diagnostic thresholds, indicating underdiagnosis; SGLT2 inhibitor use increased over time.
Methodological Strengths
- Nationwide, prospective cohort with prespecified analysis
- Phenotype-based outcomes and longitudinal therapy assessment over 3 years
Limitations
- Observational design limits causal inference on therapies
- Pre-guideline era for HFpEF may have influenced treatment patterns
Future Directions: Validate pragmatic HFpEF screening algorithms in T2D, and test comprehensive HFpEF care pathways (including SGLT2 inhibitors) in randomized or stepped-wedge designs.
BACKGROUND: Heart failure (HF) is a major complication of type 2 diabetes (T2D), with HF with preserved ejection fraction (HFpEF) now representing the most frequent phenotype. However, its clinical profile, prognosis, and treatment patterns compared with HF with reduced ejection fraction (HFrEF) remain insufficiently characterized. OBJECTIVES: To compare characteristics, outcomes, and longitudinal management of HFpEF versus HFrEF in T2D patients. METHODS: This prespecified subanalysis of the nationwide, prospective DIABET-IC cohort included 1517 patients with T2D recruited across 58 Spanish centers and fol
3. Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Non-Alcoholic Fatty Liver Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Across 21 RCTs (1,311 participants), SGLT2 inhibitors significantly improved liver steatosis (CAP, liver fat content, liver-to-spleen ratio), fibrosis surrogates (LSM, FIB-4, type IV collagen 7S), liver enzymes (ALT, AST, GGT), insulin resistance (fasting insulin, HOMA-IR), and adiposity measures (weight, BMI, visceral and subcutaneous adipose tissue), without increasing total adverse events.
Impact: Consolidates RCT evidence that SGLT2 inhibitors improve key liver and metabolic endpoints in NAFLD with an acceptable safety profile, informing therapeutic decisions in endocrinology and hepatometabolism.
Clinical Implications: Support consideration of SGLT2 inhibitors for NAFLD, especially in patients with T2D or metabolic dysfunction, while advocating for longer trials with histologic endpoints to guide guideline incorporation.
Key Findings
- SGLT2 inhibitors reduced liver steatosis indices (CAP, liver fat content, liver-to-spleen ratio) and fibrosis surrogates (LSM, FIB-4, type IV collagen 7S).
- Improved liver enzymes (ALT, AST, GGT), insulin resistance (fasting insulin, HOMA-IR), and body composition (weight, BMI, VAT, SAT).
- No significant difference in total adverse events versus control.
Methodological Strengths
- Randomized controlled trials synthesized with standard meta-analytic methods
- Broad coverage of imaging, biochemical, and metabolic endpoints
Limitations
- Use of surrogate endpoints; limited histologic confirmation across trials
- Heterogeneity in populations, durations, and background therapies
Future Directions: Conduct long-duration RCTs with biopsy-proven NASH resolution and fibrosis regression endpoints, including non-diabetic NAFLD and head-to-head comparisons with other agents.
Non-alcoholic fatty liver disease is the most common form of chronic liver disease. However, effective pharmacotherapy is still lacking. Sodium-glucose cotransporter-2 inhibitors have been proven to improve non-alcoholic fatty liver disease in previous clinical trials. In this work, an updated systematic review and meta-analysis of randomized controlled trials were performed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with non-alcoholic fatty liver disease. A literature search of PubMed, Cochrane, Web of Science, Medline, and Embase was performed up