Diabetes Obes Metab. 2026 Aug 13. doi: 10.1111/dom.71171. Online ahead of print.
ABSTRACT
IMPORTANCE: Hypercortisolism is an underdiagnosed contributor to metabolic dysfunction in people with Type 2 diabetes (T2D). Although overt Cushing syndrome is rare, milder forms of cortisol excess, commonly termed mild autonomous cortisol secretion (MACS), appear substantially more common in selected high-risk populations.
OBSERVATIONS: Chronic cortisol excess contributes directly to insulin resistance, hepatic gluconeogenesis, visceral adiposity, hypertension, dyslipidaemia and cardiovascular disease. Many patients with hypercortisolism lack classic cushingoid features and instead present with resistant diabetes, resistant hypertension, obesity or progressive cardiometabolic disease. Emerging evidence suggests that abnormal cortisol suppression following a 1-mg overnight dexamethasone suppression test (DST) occurs more frequently in patients with difficult-to-control T2D and resistant hypertension than previously appreciated. Current evidence supports a targeted case-finding approach rather than universal screening. Patients most likely to benefit from evaluation include those with persistent hyperglycaemia despite intensive therapy, severe insulin resistance, resistant hypertension, adrenal incidentalomas or physical findings suggestive of cortisol excess. The overnight 1-mg DST remains the preferred initial screening test because it is practical, inexpensive and widely available. Interpretation is supported by a confirmatory dexamethasone level ≥ 140 ng/dL and requires careful consideration of medication interactions, obesity, psychiatric disease, alcohol use, sleep disorders and assay variability.
CONCLUSIONS AND RELEVANCE: Hypercortisolism likely contributes to metabolic dysfunction in a subset of patients with T2D, particularly those with resistant cardiometabolic disease. Recognition of high-risk phenotypes and appropriate use of the DST may improve identification of patients with potentially treatable cortisol excess. Additional prospective studies are needed to clarify optimal screening strategies and determine whether earlier diagnosis and treatment improve long-term cardiometabolic outcomes.
PMID:42591054 | DOI:10.1111/dom.71171