Assessment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction: comparison of ACTH stimulation, insulin-hypoglycemia and metyrapone

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Abstract
The response to ACTH stimulation, insulin-hypoglycemia and metyrapone in patients with suspected HPA axis dysfunction due to corticosteroid therapy (Group I, n = 10), or pituitary surgery (Group II, n = 7) and in a control population (Group III, n = 8) was studied. Group I patients had been maintained on a stable low dose of prednisone 5.0–7.5 mg/day for 1 month-16 yr (mean = 31 mos) prior to testing. Basal 08:00 h cortisol levels in this group were not different from control values. However, the mean responses to all three testing procedures were suppressed (Group I vs III, ACTH p < 0.001, insulin p< 0.01, metyrapone p< 0.05). Group II patients had undergone surgery 1–26 months (mean = 10 mo) prior to testing and had been maintained subsequently on a stable dose of prednisone 5.0–7.5 mg/day. In this group basal mean 08:00 h cortisol and the cortisol response to ACTH and insulin-hypoglycemia were not significantly different from control values while the response to metyrapone was suppressed (Group II vs III p< 0.02). Basal serum DHEA-S levels were suppressed in both Groups I and II when compared to Group III (p< 0.001 ). Discordant responses to the three testing procedures were noted in 6 patients with suspected HPA dysfunction with abnormal test results in 1/6 using cortrosyn, 3/6 using insulin-hypoglycemia and 4/6 using metyrapone. We conclude that: (1) Low doses of prednisone cause subtle, but significant HPA axis suppression, (2) DHEA-S levels do not correlate with standard tests of the HPA axis, and (3) Although no single test identified every subject with an abnormal HPA axis, metyrapone was more useful in detecting subtle degrees of HPA dysfunction than ACTH or insulin-hypoglycemia. Metyrapone is simple, safe and may be the test of choice in assessing patients with suspected secondary adrenal insufficiency.