HYPOTHALMIC-PITUITARY-GONADAL AXIS FUNCTION IN PUBERTAL MALE AND FEMALE SIBLING WITH GLUCOCORTICOID-TREATED NONSALT-WASTING 3-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY CONGENITAL ADRENAL-HYPERPLASIA

We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxy-stero id dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female sibling s spontaneously developed thelarche and menarche at 10 and 12 yr, resp ectively, and manifested irregular menses, hirsutism, and polycystic o varies at 17 yr. The 16-yr-old male sibling spontaneously developed se condary sex characteristics at age 11 yr and exhibited Tanner IV-V pub ic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnod ular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min ) and gonadal steroid levels (every 2 h) under ACTH adrenal suppressio n revealed the following. In the male sibling, there were overall norm al Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, norm al peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/ mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the fe male sibling, there were normal follicular phase range LH (10-28 mIU/m L) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitu de of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH ( 62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E(2)) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal D elta(5)-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day fo r 3 days) after prolonged adrenal suppression by dexamethasone resulte d in suppression of dehydroepiandrosterone (DHEA) and E(2) in the fema le and DHEA and T in the male. Gonadal stimulation via hCG administrat ion (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E(2) response in the female (200 pmol/L; control, 2 95-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas Delta(5)-17-hydroxypregnenolone and DHEA level s rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonada l hormone secretion in these siblings indicate the absence of increase d LH secretion, in contrast to the markedly increased ACTH secretion r esulting from adrenal 3 beta HSD deficiency. The presence of enlarged testes and polycystic ovaries without increased LH secretion in the 3 beta HSD-deficient siblings remains puzzling.