Daily Endocrinology Research Analysis
Analyzed 25 papers and selected 3 impactful papers.
Summary
Three clinically relevant endocrinology studies stand out today: an international cohort clarifies outcomes-based management for bilateral adrenal tumors with cortisol excess; a large NHANES cohort shows glycated albumin outperforms HbA1c in predicting mortality among CKD patients; and a multi-ethnic prospective cohort refines the cardiovascular risk-benefit profile of menopausal hormone therapy with race/ethnicity- and metabolic status-specific nuances.
Research Themes
- Outcomes-based management of cortisol excess in bilateral adrenal tumors
- Refining glycemic risk markers in chronic kidney disease
- Race/ethnicity- and metabolism-specific effects of menopausal hormone therapy on CVD
Selected Articles
1. Effect of surgical versus conservative management on cardiovascular outcomes in patients with bilateral adrenal tumours and cortisol excess: an international, retrospective cohort study.
In 629 patients (105 Cushing’s, 524 MACS) followed for a median 6.8 years across 30 centers, mortality and cardiovascular event rates were similar across treatments, but surgery—especially bilateral adrenalectomy—achieved superior biochemical remission and improved comorbidities. Smoking was a key modifiable risk factor; in MACS managed non-specifically, higher post-dexamethasone cortisol predicted mortality, and comorbidities worsened without intervention.
Impact: This large, multi-center analysis addresses a long-standing therapeutic dilemma in adrenal endocrinology and provides comparative outcome data to inform surgical versus conservative strategies.
Clinical Implications: Consider surgery for selected patients—particularly bilateral adrenalectomy when feasible—for better biochemical control and comorbidity improvement, while mitigating adrenal crisis risk with structured education and replacement. Prioritize smoking cessation. Avoid long-term conservative management in MACS with worsening comorbidities and elevated post-dexamethasone cortisol.
Key Findings
- Among 629 patients (105 Cushing’s, 524 MACS), 7% died and 12–16% had cardiovascular events over 6.8 years, with similar event rates across treatments.
- Bilateral adrenalectomy achieved full biochemical remission with few non-fatal adrenal crises and improved hypertension; unilateral adrenalectomy or steroidogenesis inhibitors showed heterogeneous biochemical effects.
- Non-specific symptomatic treatment in MACS was associated with worsening of all investigated comorbidities; smoking was a key modifiable risk factor, and higher post-dexamethasone cortisol predicted mortality in conservatively managed MACS.
Methodological Strengths
- Large, international multi-center cohort with long-term follow-up.
- Comprehensive clinical and biochemical endpoints including cardiovascular events and adrenal crises.
Limitations
- Retrospective, non-randomized treatment allocation with potential selection bias.
- Heterogeneity of interventions and limited granularity on perioperative management.
Future Directions: Prospective comparative trials or pragmatic registries to define optimal surgical strategies versus medical therapy in MACS and Cushing’s; standardized protocols to minimize adrenal crises and evaluate quality-of-life outcomes.
BACKGROUND: Treatment for patients with bilateral adrenal tumours and cortisol excess is not standardised and poses a therapeutic dilemma. Untreated cortisol excess is associated with cardiometabolic morbidity and mortality, but bilateral adrenalectomy causes adrenal insufficiency and possibly life-threatening adrenal crises. Data on cardiovascular outcomes by treatment modality are scarce. In this study we aimed to evaluate mid-term and long-term clinical and biochemical outcomes in patients with bilateral adre
2. Hormone Replacement Therapy and Cardiovascular Outcomes by Race and Ethnicity: MESA (Multi-Ethnic Study of Atherosclerosis).
In 2,427 postmenopausal women followed for a median of 14 years, HRT initiation within 5 years of menopause was associated with lower MACE (HR 0.72) and all-cause mortality (HR 0.62). However, Chinese women with metabolic syndrome or elevated triglycerides experienced increased MACE risk on HRT (HR 2.27), highlighting race/ethnicity- and metabolism-specific heterogeneity.
Impact: This study refines the timing hypothesis for HRT by integrating race/ethnicity and metabolic phenotype, informing precision cardiovascular risk assessment in menopausal therapy.
Clinical Implications: Early HRT may reduce MACE and mortality in most groups, but clinicians should avoid or use extreme caution in Chinese women with metabolic syndrome or hypertriglyceridemia. Tailor HRT decisions to metabolic profile, ethnicity, and baseline CVD risk, and monitor lipids and cardiometabolic markers closely.
Key Findings
- HRT within 5 years of menopause was associated with lower MACE (HR 0.72, 95% CI 0.55–0.96) and all-cause mortality (HR 0.62, 95% CI 0.48–0.80).
- Chinese participants on HRT had increased MACE (HR 2.27, 95% CI 1.06–4.87) and a trend toward higher mortality, limited to those with metabolic syndrome or elevated triglycerides.
- Findings support the timing hypothesis while emphasizing race/ethnicity- and metabolic-specific risk stratification.
Methodological Strengths
- Prospective, multi-ethnic cohort with long follow-up and adjudicated outcomes.
- Cox modeling incorporating timing of HRT initiation and race/ethnicity interactions.
Limitations
- Observational design with potential residual confounding and indication bias.
- Limited power for subgroup analyses, especially within Chinese participants with specific metabolic profiles.
Future Directions: Randomized or pragmatic trials stratified by metabolic phenotype and ethnicity; mechanistic studies on triglyceride-rich lipoproteins, inflammation, and vascular response under HRT.
BACKGROUND: There is mixed data regarding hormone replacement therapy (HRT) and cardiovascular disease (CVD), particularly on how timing of HRT initiation close to menopause may affect outcomes, and there is little data among different race/ethnicity groups. OBJECTIVE: The purpose of this study was to how HRT use and cardiovascular outcomes differ by race/ethnicity. METHODS: The Multi-Ethnic Study of Atherosclerosis is a prospective epidemiologic study of participants without CVD at enrollment. Outcomes were (1) all-cause mortality and (2) major adverse cardiovascular events (MACEs). Cox models were developed, focusing on the timing of HRT initiation and differences by race/ethnicity (White, Black, Hispanic, and Chinese). RESULTS: There were 2,427 postmenopausal women with data on HRT and outcomes, followed up for a median of 14 years. HRT use within 5 years of menopause was associated with decreased MACE and all-cause mortality (HR: 0.72 [95% CI: 0.55-0.96] and HR 0.62 [95% CI: 0.48-0.80], respectively). These findings differed by racial/ethnic groups, with Chinese participants on HRT having increased MACE and a trend towards increased mortality (HR: 2.27 [95% CI: 1.06-4.87] and HR: 1.34 [95% CI: 0.73-2.47], respectively). These findings were only seen in Chinese participants who had the metabolic syndrome or elevated triglyceride levels. CONCLUSIONS: We found relative benefit with early initiation of HRT in all race/ethnic groups except Chinese, adding to the complex literature on HRT use in CVD primary prevention. However, Chinese women with the metabolic syndrome or elevated triglycerides may have increased risk of adverse cardiovascular outcomes with HRT, suggesting further research is needed on racial and metabolic differences in the cardiovascular impact of HRT use.
3. The predictive value of glycated albumin and hemoglobin A1c for all-cause and cardiovascular mortality in chronic kidney disease patients.
In 2,433 CKD participants followed for a median of 12.46 years, glycated albumin had stronger, more linear associations with all-cause and cardiovascular mortality than HbA1c and improved risk discrimination and reclassification (C-index, NRI, IDI). The advantage of GA was particularly evident in earlier CKD stages.
Impact: This analysis challenges the default reliance on HbA1c in CKD by demonstrating superior prognostic performance of glycated albumin for hard outcomes.
Clinical Implications: In CKD care, consider incorporating glycated albumin alongside or in place of HbA1c for mortality risk stratification, particularly in earlier stages, while accounting for conditions affecting albumin turnover.
Key Findings
- Among 2,433 CKD participants, 1,532 all-cause deaths (63%) and 473 cardiovascular deaths (19%) occurred over 12.46 years.
- GA showed positive linear associations with all-cause and cardiovascular mortality and outperformed HbA1c in discrimination and reclassification (C-index, NRI, IDI).
- The prognostic advantage of GA was most pronounced in earlier CKD stages.
Methodological Strengths
- Nationally representative cohort with long follow-up and weighted Cox analysis.
- Head-to-head prognostic comparison using C-index, NRI, and IDI with spline modeling for dose-response.
Limitations
- Observational design with potential residual confounding and measurement variability.
- Single baseline measurements and possible influence of albumin turnover/inflammation on GA levels.
Future Directions: Prospective validation across CKD stages, definition of GA thresholds for clinical decision-making, and trials testing GA-guided interventions.
BACKGROUND: The reliability of hemoglobin A1c (HbA1c) as a glycemic marker is limited in chronic kidney disease (CKD), which has led to increased interest in glycated albumin (GA). This study aimed to compare the associations of GA and HbA1c with mortality. METHODS: This prospective study used data from the National Health and Nutrition Examination Survey (1999-2004). Cox proportional hazards regression analysis with weight adjustment and restricted cubic spline regression were used to examine the associations between GA/HbA1c and mortality. The discriminative performance of GA and HbA1c for mortality was assessed via the concordance index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1,532 (62.97%) all-cause deaths and 473 (19.44%) cardiovascular (CV) deaths among the 2,433 participants with CKD occurred over a median of 12.46 years of follow-up. The associations between GA and all-cause mortality as well as CV mortality showed a positive linear pattern (P CONCLUSIONS: GA is more strongly associated with mortality than HbA1c in patients with CKD, particularly in the early stages, highlighting its potentially complementary value in clinical practice.