Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors

The objective of this study was to determine whether a low dose of ACTH (0.2 microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic-pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and skull-based tumors. Twenty-two children who had undergone treatment for brain or skull-based tumors were enrolled in a prospective study to extensively evaluate the HPA axis. Five tests of the adrenal axis were evaluated in each patient, including determination of basal serum cortisol, a standard ACTH test (250-microg i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin tolerance test, and a single dose metyrapone test. Cortisol responses to both ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH test, whereas three (14%) failed the standard ACTH test; five of the children (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to metyrapone. One child who initially passed the metyrapone test failed the test 19 months later after becoming symptomatic. All children with abnormal metyrapone test results had low levels of basal cortisol secretion. In this study, the low dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of the HPA axis. We conclude that a single morning basal cortisol level is a good screen for testing the HPA axis in children. We recommend confirming HPA axis dysfunction with the single dose metyrapone test, although this test also has limitations.