Rethinking hypercortisolism screening in obesity and diabetes: A systematic review and meta-analysis

The growing burden of obesity and diabetes underscores the need for innovative strategies to identify secondary causes. While hypercortisolism is traditionally considered rare, its broader spectrum - from mild autonomous cortisol secretion to overt Cushing's syndrome (CS) - may be under-recognized in these populations.

We systematically searched MEDLINE, Scopus and Web of Science for original studies assessing hypercortisolism in obesity or diabetes. We included first-line screening tests for hypercortisolism, particularly the dexamethasone suppression test (DST), and subsequent confirmed CS. Data were pooled using random-effects models and are presented as 95%CIs. Certainty of evidence was assessed with GRADE.

Of 3038 articles, 39 (14,995 screened participants) were included. In a pooled cohort of 8705 individuals with obesity (19 studies), the prevalence of an abnormal DST was 4.6% (95%CI: 3.2-6.4), and CS confirmed in 0.8% [0.4-1.5]. Among 6638 patients with diabetes (22 studies), 14.3% (95%CI: 10.9-18.4) had an abnormal DST, increasing to 23.3% (95%CI: 22.2-24.5) after heterogeneity adjustment; 2.1% (95%CI: 1.3-3.3) had confirmed CS. Age, recent weight gain, and diabetes were significant predictors of CS. One in seven abnormal DST led to CS confirmation. Exploratory economic analyses supported broadening screening in selected cohorts. GRADE certainty ranged from low to moderate.

In a clinically relevant subset of patients with obesity and diabetes, underlying hypercortisolism remains undiagnosed. The implications of abnormal DST without confirmed CS warrant further investigation. Screening strategies for secondary causes of obesity and type 2 diabetes might require reassessment, pending confirmation in unbiased cohorts.