Evidence of persistent mild hypercortisolism in patients medically treated for Cushing's disease: the Haircush study.

Abstract

Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing's disease (CD). Assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and -cortisone (HE) measurement. Multicenter prospective study. Three groups of female patients: CushMed=16 treated with a stable cortisol-lowering drug dosage and normal UFCs; CushSurg=13 cured by pituitary surgery; CushBla=15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy. Patients were evaluated during 3 months with their usual treatments. Two late-night saliva and 24h urine samples were monthly collected in CushMed, and at study end in CushSurg and CushBla patients. A 3-cm hair sample was collected at study end in all patients. Clinical score and centralized measurement of UFC, late-night salivary cortisol (LNSF) and -cortisone (LNSE), HE, HF. Despite having almost all UFCs normalized, CushMed patients exhibited increased HE as compared to CushSurg controls (p=0.003). CushMed patients also had increased clinical score (p=0.001), UFC (p=0.03), LNSF, LNSE (p=0.0001) and variability in the latter parameters (p=0.004). CushBla patients had increased HF and HE contrasting with similar LNSE to CushSurg patients. Six of 15 CushMed patients exhibited increased HE concentrations and had increased antihypertensive drug dosage compared to CushMed patients with normal HE (p=0.05). Despite normalized UFCs, a subset of medically-treated CD patients displays an altered circadian rhythm of serum cortisol. A single HE measurement identifies chronic mild persistent hypercortisolism and could replace multiple saliva analyzes to monitor medical treatments in CD patients once UFC is normalized.