Daily Endocrinology Research Analysis
Analyzed 29 papers and selected 3 impactful papers.
Summary
Analyzed 29 papers and selected 3 impactful articles.
Selected Articles
1. Seated Saline Suppression Test for Lateralizing Primary Aldosteronism.
In a blinded, prospective diagnostic study of 160 high-risk primary aldosteronism patients, the seated saline suppression test showed only modest accuracy for predicting adrenal vein sampling lateralization, with weak positive likelihood ratios (1.1–1.9) and limited rule-out performance. Findings were consistent across immunoassay and LC-MS/MS thresholds, indicating aldosterone suppression testing is unreliable for lateralization.
Impact: This study challenges the clinical utility of a widely used confirmatory test for primary aldosteronism lateralization, potentially reshaping diagnostic pathways toward more definitive approaches.
Clinical Implications: Avoid using SSST to guide decisions about unilateral adrenalectomy; proceed directly to adrenal vein sampling for lateralization in high-risk PA. Reconsider reliance on aldosterone suppression thresholds for surgical triage.
Key Findings
- Among 160 patients, 61.3% had lateralizing PA by AVS.
- SSST diagnostic accuracy was 64.4% at ≥140 pmol/L and 67.5% at ≥280 pmol/L postinfusion aldosterone.
- Positive likelihood ratios were weak (1.1–1.9); negative likelihood ratios were 0.3–0.5.
- Performance was similar using immunoassay and LC-MS/MS thresholds.
Methodological Strengths
- Blinded, prospective diagnostic design with adrenal vein sampling as gold standard.
- Pre-specified aldosterone thresholds and assessment using both immunoassay and LC-MS/MS; trial registered (NCT04422756).
Limitations
- Diagnostic accuracy was modest; findings may reflect a high-risk referral population.
- Non-randomized diagnostic study; potential spectrum effects across centers and assays.
Future Directions: Develop and validate alternative noninvasive lateralization tools (imaging or biochemical panels), and assess cost-effectiveness of direct-to-AVS strategies.
BACKGROUND: Confirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit. METHODS: Blinded clinical trial where patients with high-risk features for PA underwent the seated saline suppression test (SSST). All patients received adrenal vein sampling, where lateralization was defined by an aldosterone/cortisol ratio ≥3:1 comparing the dominant versus the nondominant sides. The primary outcome was the overall diagnostic accuracy of the SSST in identifying lateralizing PA using postinfusion aldosterone concentrations of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) with immunoassay, and ≥162 pmol/L (5.8 ng/dL) with liquid chromatography/tandem mass spectrometry. RESULTS: A total of 160 patients completed the trial. Lateralizing PA was diagnosed in 98 patients (61.3%). The overall diagnostic accuracy of the SSST using an aldosterone cutoff of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) was 64.4% (95% CI, 56.4-71.8) and 67.5% (95% CI, 59.7-74.7), respectively. A positive result was equivocal at the lower cutoff of ≥140 pmol/L (5.0 ng/dL; positive likelihood ratio, 1.1 [95% CI, 1.0-1.3]) and minimally informative at the higher cutoff of ≥280 pmol/L (10.1 ng/dL; positive likelihood ratio, 1.9 [95% CI, 1.3-2.7]). Negative results modestly ruled against lateralization using cutoffs of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL; negative likelihood ratio, 0.3 [95% CI, 0.1-0.9]; and 0.5 [95% CI, 0.3-0.7], respectively). The SSST properties were similar with liquid chromatography/tandem mass spectrometry. CONCLUSIONS: Aldosterone suppression testing is unreliable for anticipating adrenal vein sampling outcomes. The SSST may misinform diagnostic-treatment decisions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04422756.
2. Effect of empagliflozin on urinary albumin excretion and hypoxic biomarkers in early diabetic kidney disease: A randomised double-blind, placebo-controlled trial.
In a 24-week multicenter randomized double-blind trial in type 2 diabetes with microalbuminuria (n=79), empagliflozin did not significantly reduce ACR versus placebo at 24 weeks despite earlier improvements, and it did not affect urinary L-FABP. However, serum VEGF and ANGPTL2 decreased significantly, supporting a hypoxia/angiogenesis-related renoprotective mechanism.
Impact: This rigorously designed RCT provides mechanistic evidence linking SGLT2 inhibition to suppression of hypoxia-induced angiogenic signaling in early DKD, complementing clinical renal benefits observed in outcome trials.
Clinical Implications: While short-term albuminuria change was limited at 24 weeks, the biomarker profile supports renoprotective mechanisms; clinicians should continue SGLT2 inhibitors for kidney protection while recognizing biomarker shifts may precede sustained albuminuria changes.
Key Findings
- ACR reduction favored empagliflozin at 4 and 12 weeks, but not at 24 weeks (between-group difference p=0.0686).
- No between-group difference in urinary L-FABP at 24 weeks.
- Serum VEGF and ANGPTL2 decreased significantly more with empagliflozin; AM and ANGPTL4 did not differ.
Methodological Strengths
- Multicenter randomized double-blind placebo-controlled design with pre-registration (jRCTs051200147).
- Pre-specified primary and secondary biomarker endpoints enabling mechanistic inference.
Limitations
- Modest sample size and 24-week duration limit power to detect sustained albuminuria changes.
- Biomarker endpoints without hard renal outcomes; microalbuminuria-only population may limit generalizability.
Future Directions: Larger, longer RCTs linking hypoxia/angiogenesis biomarker modulation to renal endpoints; explore dose-response and timing of albuminuria changes.
AIMS: The precise mechanism of sodium glucose co-transporter 2 (SGLT2) inhibitor on reno-protective effect has been still unclear. In this study, we hypothesised that SGLT2 inhibitor prevents diabetic kidney disease via reduction of hypoxia-induced factors. MATERIALS AND METHODS: In this multicenter, prospective, randomised, double blinded clinical trial, people with type 2 diabetes and microalbuminuria were randomised equally to empagliflozin (10 mg/day) (n = 40) and placebo (n = 39) and followed 24 weeks. The primary endpoint was change in urinary albumin creatinine ratio (ACR) and urinary liver type fatty acid binding protein (L-FABP) excretion from baseline to 24 weeks. Major secondary outcome was change in serum vascular endothelial growth factor (VEGF), angiopoietin-like proteins 2 (ANGPTL2), angiopoietin-like proteins 4 (ANGPTL4), and adrenomedullin (AM) levels. RESULTS: Although the reduction of ACR was significantly greater in the empagliflozin group than the placebo group at 4 and 12 weeks, the difference of change at 24 weeks between the two groups was not statistically significant (Empagliflozin group-Placebo group: -0.3643, 95% CI: -0.7571 to 0.0285, p = 0.0686). There was no difference in urinary L-FABP excretion between the empagliflozin and placebo groups. Serum VEGF and ANGPTL2 decreased significantly more in the empagliflozin group, whereas there were no significant differences in AM and ANGPTL4. CONCLUSIONS: These results demonstrated that empagliflozin partially suppressed the hypoxia-induced angiogenic factors overproduction in addition to a declining trend in ACR in the early stage of diabetic kidney disease, which might contribute to the mechanisms of reno-protective effects of this agent (jRCTs051200147).
3. An oral glucose tolerance test in pregnancy and its association with future cardiovascular diseases.
In a retrospective cohort of 103,389 pregnancies with a median 6.8-year follow-up, the risk of incident cardiovascular disease increased with the number of abnormal 100-g OGTT values: adjusted HR 1.2 for 1–3 abnormal values and 2.41 for four abnormal values versus normal. These findings highlight pregnancy OGTT as a marker for postpartum cardiovascular risk stratification.
Impact: This large-scale analysis quantitatively links the burden of pregnancy OGTT abnormalities to long-term CVD risk, offering a pragmatic risk signal to trigger early postpartum prevention.
Clinical Implications: Women with multiple abnormal OGTT values—especially four—should receive early cardiovascular risk assessment and prevention postpartum, including lifestyle, BP/lipid screening, and longitudinal follow-up.
Key Findings
- Among 103,389 individuals (median follow-up 6.8 years), 641 developed incident CVD (0.62% cumulative incidence).
- Adjusted HR for CVD was 1.2 with 1–3 abnormal OGTT values versus normal.
- Adjusted HR for CVD rose to 2.41 with four abnormal OGTT values.
- 886,955 person-years of follow-up provided robust statistical power.
Methodological Strengths
- Very large population-based cohort with long follow-up and Cox modeling.
- Standardized 100-g OGTT across participants enabling gradient-of-risk analyses.
Limitations
- Retrospective design with potential residual confounding and outcome misclassification from administrative data.
- Lack of detailed postpartum behavioral or treatment data that could modify CVD risk.
Future Directions: Prospective studies to test targeted postpartum CVD prevention strategies based on OGTT abnormality burden; integrate risk scoring into obstetric-endocrine care pathways.
AIMS/HYPOTHESIS: Gestational diabetes and abnormal 100-g oral glucose tolerance test (OGTT) results in pregnancy are associated with type 2 diabetes, but their relationship with cardiovascular disease (CVD) is less clear. We evaluated the risk of CVD according to the number of abnormal OGTT values during pregnancy. METHODS: This retrospective cohort study used data from a major Israeli healthcare provider. Pregnant individuals aged 20-50 years without a prior diagnosis of type 2 diabetes and CVD who had a complete 100-g OGTT during their last pregnancy between January 2000 and December 2022 were included. The primary outcome was the development of a composite of CVD by September 2024. Risk was assessed using Cox proportional hazards models based on the number of abnormal OGTT values. RESULTS: The study included 103 389 individuals with a mean age of 34 ± 5.2 years. Overall, the median follow-up was 6.8 years (IQR, 3.4-12.9), totalling 886 955 person-years. A composite of CVD developed in 641 individuals (a cumulative incidence of 0.62%). When compared to individuals with all OGTT values normal, individuals with one to three abnormal values had an adjusted hazard ratio (HR) of 1.2 (95% CI: 1.02-1.4) for CVD, reaching 2.41 (95% CI 1.44-4.05) in those with four abnormal OGTT values. CONCLUSIONS: A history of abnormal 100-gram OGTT results during pregnancy, and specifically having four abnormal values, is associated with an elevated risk of CVD. These results underscore the need for early post-partum identification and prevention strategies in this high-risk population.