Adrenal androgen response to metyrapone, adrenocorticotropin, and corticotropin-releasing hormone stimulation in children with hypopituitarism.
We determined the adrenal steroid responses to metyrapone, ACTH, and CRH in 12 ACTH-intact and 5 ACTH-deficient hypopituitary children to determine the mechanisms that control adrenal androgen secretion. Serum adrenal androgen concentrations [dehydroepiandrosterone (DHEA) and delta 4-androstenedione (delta 4-A)] rose in response to oral administration of metyrapone (450 mg/m2 X dose, every h for 7 doses) in ACTH-intact hypopituitary children with multiple or isolated pituitary hormone deficiencies [mean postmaryrapone level: DHEA, 225 ng/dL (range, 27-566); delta 4-A, 313 ng/dL (range, 105-651)], except in 2 young children in whom DHEA did not rise. These adrenal androgens did not rise in all ACTH-deficient hypopituitary children [mean postmetyrapone level: DHEA, 11.0 ng/dL (range, 3-16); delta 4-A, 6.2 ng/dL (range, 3-10)]. The increases in both serum cortisol and adrenal androgens, including DHEA sulfate, in response to short term ACTH infusion (40 U in 6 h) in ACTH-intact hypopituitary children were normal or above normal, while these steroid responses were significantly (P less than 0.05-0.01) lower in ACTH-deficient hypopituitary children compared to normal values. However, prolonged administration of ACTH (40 U/day, or im) for 6 days to 2 ACTH-deficient hypopituitary children resulted in normal DHEA responses to the 6-h ACTH stimulation test (DHEA levels after the first test, 14 and 30 ng/dL, after priming, 80 and 50 ng/dL). Furthermore, CRH administration to 4 ACTH-deficient patients caused a rise in serum DHEA and cortisol in patients with a normal ACTH response, while those with a poor ACTH response had a lesser rise in DHEA and cortisol. These data suggest that ACTH is the major tropic hormone for adrenal androgen secretion.
D000293:Adolescent; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000728:Androgens / Q000097:blood / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007018:Hypopituitarism / Q000378:metabolism*; D007223:Infant; D008297:Male; D008797:Metyrapone; D008901:Mineralocorticoids / Q000378:metabolism
D000728:Androgens; D005938:Glucocorticoids; D008901:Mineralocorticoids; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008797:Metyrapone