Low- and standard-dose corticotropin and insulin hypoglycemia testing in the assessment of hypothalamic-pituitary-adrenal function after pituitary surgery

The optimal means of assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis after pituitary surgery remains controversial. We compared low-dose (1 mug iv) and standard-dose (250 mug im) corticotropin tests performed 1 and 4-6 wk after pituitary surgery with an insulin hypoglycemia test performed at 4-6 wk. Forty-one patients (21 male and 20 female; median age, 52 yr; range, 23-73 yr) who had undergone pituitary surgery were studied (Cushing's disease excluded). Twenty-two of the 41 patients had normal cortisol responses to all tests both at 1 and 4-6 wk after surgery. Eight patients had subnormal cortisol responses to all tests. Of the 11 patients with discrepant results, seven had subnormal responses only after the low-dose corticotropin test; the remaining four patients had borderline responses to one or more tests. At 4-6 wk after surgery, subjects with a 30-min serum cortisol after standard-dose corticotropin of less than 350 nmol/liter (12.7 mug/dl) consistently had a subnormal response to hypoglycemia, and those with a serum cortisol greater than 650 nmol/liter (23.6 mug/dl) had a normal response to hypoglycemia. Definitive testing of the HPA axis using the standard-dose corticotropin test can be carried out provided it is performed at least 4 wk after pituitary surgery. A 30-min cortisol level greater than 650 nmol/liter (23.6 mug/dl) indicates adequacy of the HPA axis, and a level of less than 350 nmol/liter (12.7 mug/dl) indicates ACTH deficiency. No further testing is then required. An intermediate level of 350-650 nmol/liter (12.7-23.6 mug/dl) warrants further assessment using the insulin hypoglycemia test.