Hair cortisol as a complementary marker of chronic glucocorticoid exposure in mild autonomous cortisol secretion

Mild autonomous cortisol secretion is a subtle yet clinically relevant form of cortisol excess linked to increased cardiometabolic risk. Conventional biochemical tests capture short-term hypothalamic–pituitary–adrenal axis activity and may not reflect cumulative exposure. Hair cortisol concentration has been proposed as a long-term biomarker, but evidence in mild autonomous cortisol secretion is limited. To compare hair cortisol concentration between patients with mild autonomous cortisol secretion and healthy controls, assess diagnostic performance, and examine associations with hormonal and metabolic parameters. In this cross-sectional study, 73 patients with mild autonomous cortisol secretion and 60 rigorously screened controls were included. Mild autonomous cortisol secretion was defined according to European Society of Endocrinology guidelines. Hair cortisol concentration was measured from the proximal 3-cm hair segment. Assessments included the 1-mg overnight dexamethasone suppression test, 2-day 2 mg dexamethasone suppression test, 24-hour urinary free cortisol, and late-night salivary cortisol. Correlation and receiver operating characteristic analyses were performed. Hair cortisol concentration was significantly higher in patients with mild autonomous cortisol secretion than in controls (median 3.6 vs. 1.75 ng/g; p < 0.01). In patients with mild autonomous cortisol secretion, hair cortisol concentration correlated with waist circumference (ρ = 0.27; p = 0.02) and late-night salivary cortisol (ρ = 0.25; p = 0.03), but not with dexamethasone suppression test-based measures or urinary cortisol. Receiver operating characteristic analysis showed modest discrimination (AUC = 0.60, 95% CI 0.51–0.70, p = 0.025); the 2.7-ng/g cut-off yielded limited sensitivity and specificity. In multivariable logistic regression adjusted for age, sex, and body mass index, hair cortisol concentration was not independently associated with mild autonomous cortisol secretion. Hair cortisol concentrations were higher in patients with mild autonomous cortisol secretion than in healthy controls, suggesting that hair cortisol concentration may capture some aspects of chronic glucocorticoid exposure in this population. However, its diagnostic performance was modest, and hair cortisol concentration was not independently associated with mild autonomous cortisol secretion after adjustment for age, sex, and body mass index. Therefore, hair cortisol concentration should be regarded as a complementary rather than a standalone biomarker, and further prospective studies are needed to clarify its clinical utility.