Hypogonadism in congenital adrenal hypoplasia: evidence for a hypothalamic origin

Two unrelated boys with congenital adrenal hypoplasia were followed from birth for 20 yr. In spite of continuous treatment with hydrocortisone and fluorocortisone both patients had delayed growth and bone maturation since early childhood and failure of spontaneous puberty. Tests of the hypothalamic-pituitary function showed low basal plasma LH and FSH levels and blunted LH and FSH responses to standard GnRH tests and increased basal and TRH-stimulated PRL levels. Low dose pulsatile GnRH administration for 26 h, mimicking presumed physiological GnRH secretion, induced a continuing rise of plasma FSH in both patients and a slight increase of plasma LH and testosterone in one patient. These results indicate a hypothalamic origin of the gonadotropin deficiency with possible prenatal onset, since both patients had cryptorchidism during infancy. Hypogonadism in patients with adrenal hypoplasia may result from deficient steroid secretion of the hypoplastic fetal adrenals.