An Evaluation of the Distinction of Ectopic and Pituitary ACTH Dependent Cushing's Syndrome by Clinical Features, Biochemical Tests and Radiological Findings

The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ 30 mmol/l; serum cortisol at 9 a.m. or midnight of > 800 nmol/l; urine free cortisol > 1300 nmol/24 hours; plasma ACTH > 100 ng/1. In the high-dose dexamethasone suppression test, suppression by 450nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of < 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of ≤3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was >3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease ( Patient 16 ); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measuranle plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH.