Hypogonadotropic Hypogonadism Associated with Retinitis Pigmentosa in a Female Sibship: Evidence for Gonadotropin Deficiency*

Three hypogonadotropic female siblings, aged 19, 19 (twins), and 22 yr, with primary amenorrhea, lack of secondary sexual development, and retinitis pigmentosa were evaluated to determine hypothalamic-pituitary-ovarian function and anterior pituitary hormone release. Spontaneous LH, FSH, PRL, TSH, GH, cortisol (F), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) secretory patterns were determined by assay of hourly blood samples obtained over a 24-h period. Studies of stimulated release of anterior pituitary hormones included: gonadotropin response to LRF (two 10 µg iv pulses at 2-h intervals) before and after 1) estradiol benzoate (5 µg/kg- 12 h, im for 5 days) and 2) repetitive low dose LRF (0.025 µg/kg. 2 h, iv for 5 days); PRL and TSH responses to TRH (500 µg iv bolus); and GH and F responses to an insulin tolerance test (0.1 U/kg). Ethinyl estradiol (50 µg/day, orally) was administered for 4 weeks, after which endocrine evaluation was repeated. The mean basal levels of LH and FSH were similar to those in pubertal and prepubertal children. Episodic gonadotropin release was attenuated in two subjects, and a nyctohemeralrhythm was absent in all three. The administration of estradiol benzoate or repetitive low dose LRF failed to augment spontaneous or stimulated gonadotropin release. PRL secretion was diminished and was unaltered with sleep. The PRL response to TRH was decreased compared to that in normal women. GH secretion was attenuated and was not stimulated by insulininduced hypoglycemia. The mean basal levels of DHEA and DHEA-S were consistent with pubertal staging. The administration of ethinyl estradiol enhanced the spontaneous secretion of PRL and F and augmented the stimulated release of PRL, TSH, GH, and F. Hypogonadism was confirmed by low serum estradiol levels. In response to human menopausal gonadotropin, a marked rise in estradiol occurred. These results indicate that hypogonadism in these subjects is due in part to pituitary gonadotropin deficiency. Diminished PRL and possibly GH secretion were related to hypoestrogenism resulting from chronic hypogonadism. The lack of endogenous estrogen did not appear to influence spontaneous TSH or ACTH release. Retinitis pigmentosa and the familial occurrence suggested an inherited disorder.