Diagnosis of Acth Deficiency: Low Dose and One-Hour Acth Test Versus Overnight Metyrapone Test † 474

Identification of ACTH deficiency is critical for health care of patients with hypopituitarism or after radiation therapy. We evaluated the hypothalamic-pituitary-adrenal axis in 127 children at risk for ACTH deficiency because of cranial tumor or leukemia, CNS disorders, or growth hormone deficiency.

METHODS: Study 1: High dose ACTH: 38 children were given 250μg/m² ACTH iv (maximum 250 μg, blood drawn for cortisol at 0& 60 min). At 2400 they were given metyrapone orally (1g/m² if<30 kg, 1g if 30 to 60 kg, 3g if >60 kg; blood drawn for 11 deoxycortisol & cortisol at 0800 h). Study 2: Low dose ACTH: 89 children were given 1 μg/m² ACTH iv (maximum 1 μg, blood drawn for cortisol at 0 & 20 min), followed by metyrapone test as above.

RESULTS: Study 1: Of the 38 children at risk, 21 had normal responses to both tests & 14 had low compound S response (<7μg/dL) to metyrapone. Of these only 3 had low cortisol response (<20μg/dL) to ACTH. Study 2: Of the 89 children at risk, 45 had normal responses to both tests & 18 had low response to metyrapone. These 18 and 13 others had low cortisol response(<20μg/dL)to ACTH. Of those with normal metyrapone tests, 11 had borderline cortisol response (17-20μg/dL) to ACTH.

CONCLUSIONS: High dose ACTH testing misses most patients who require hydrocortisone therapy at times of stress (21% sensitivity, 63% accuracy). In contrast, low dose ACTH testing provides 100% sensitivity and 86% accuracy for ACTH deficiency. 26% of such patients would require follow-up testing with metyrapone. We conclude that the metyrapone test is more sensitive than the high dose ACTH test and remains the definitive test for assessment of adequate ACTH reserve. The low dose ACTH test serves as an accurate first line test. The low dose ACTH test serves as an accurate first line test.