SCRUTINY of the adrenocortical steroids excreted in the urine of patients with the adrenogenital syndrome (due to congenital adrenal hyperplasia) has afforded an opportunity to localize the biochemical defects attributable to an inborn error of metabolism and has elucidated the normal pathway for biosynthesis in the adrenal gland in man. The studies of Hechter on the biogenesis of hydrocortisone in the beef adrenal has indicated a stepwise oxidation of progesterone toward the fulfillment of the requirements for the final product, namely hydrocortisone. Hydrocortisone is indeed a "final product" in the economy of the pituitary adrenal axis: When its rate of secretion is low, larger amounts of adrenocorticotropin (ACTH) are released in an attempt to stimulate the adrenal cortex. If the target gland cannot properly synthesize hydrocortisone, the pituitary continues to stimulate the gland, which produces large quantities of "abnormal" intermediary metabolites. Certain of these latter substances are androgenic and account for the clinical manifestations.
An oxygen function must be introduced into the progesterone molecule at carbons 17, 21 and 11 in order for the adrenal cortex to manufacture hydrocortisone. The oxygen is introduced at each position, presumably under the control of separate enzymes tentatively termed "hydroxylases" and specified by the position they affect. If one or more of these enzymes is lacking, hydrocortisone is not produced, or is synthesized in limited quantities. Depending upon the particular enzymatic defect, the unusual metabolites measured in the blood and urine vary, as does the type of disease encountered.
In all forms of the adrenogenital syndrome virilization is present.
- Copyright © 1958 by the American Academy of Pediatrics