Suppressibility of Plasma Adrenocorticotropin by Hydrocortisone: Potential Usefulness in the Diagnosis of Cushing’s Disease1

Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with Cushing's disease led to the present study of the prevalence of this phenomenon in 58 patients with otherwise incontrovertible evidence of Cushing's disease. Because as many as 23% of these patients manifested this phenomenon, we investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients and 16 controls. The data showed invariable suppression of plasma ACTH to < or = 10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same times in 14/14 patients with active Cushing's disease, including 3 patients whose cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7 patients with intermittent hypercortisolism. Occasional variations in plasma cortisol elevations after the oral dose require that plasma cortisol concentration be monitored at 60 min after the oral hydrocortisone dose, because the present evidence supports the validity of the conclusion that a plasma ACTH concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of ACTH suppressibility by cortisol would be worthwhile, to confirm its potential value in facilitating positive diagnosis of Cushing's disease when dexamethasone suppressibility seems misleading.