A comparison between short ACTH and insulin stress tests for assessing hypothalamo-pituitary-adrenal function

Insulin-induced hypoglycaemia is the standard method for assessment of the hypothalamo-pituitary-adrenal (HPA) axis of patients with pituitary or hypothalamic disease. It has been claimed that a normal cortisol response to the 30-minute ACTH stimulation test (AST) obviates the need to perform the insulin stress test (IST) in these patients. The objective of our study was to compare both tests in a group of consecutive patients with pituitary disease.

Thirty patients with pituitary disease were evaluated by standard IST (0.1 U of soluble insulin/kg body weight, i.v.) after fasting from midnight and AST (250 micrograms synacthen, i.v.). In the IST, a plasma glucose of < 2.2 mmol/l was taken as the hypoglycaemic threshold and blood was collected at 0, 30, 60, 90 and 120 minutes. In the AST blood was collected at 0 and 30 minutes. Serum cortisol was measured by standard radioimmunoassay and glucose by the glucose oxidase method. Cortisol responses to the stimuli were compared at cut-off levels of 550, 500, 450 and 400 nmol/l.

At 550 nmol/l, out of 30 patients, 17 showed an abnormal IST of whom 9 had normal responses to AST (53%). At 500 nmol/l, 12 patients had an abnormal IST of whom 6 had normal AST (50%). At 450 nmol/l, of 9 patients with an abnormal IST, 5 had a normal AST (56%). At 400 nmol/l, 5 patients had an abnormal IST all of whom (100%) showed a normal AST.

There is a clear discrepancy between the results of the two tests at different cortisol cut-off levels. The ACTH stimulation test is not reliable for assessing the HPA axis in patients with pituitary disease and the insulin stress test remains the standard method.