Repetitive Infusion of Gonadotropin-Releasing Hormone Distinguishes Hypothalamic from Pituitary Hypogonadism*

Abstract

Patients who have severe hypogonadotropic hypogonadism caused by presumed hypothalamic disease often have a subnormal LH response to a bolus dose of gonadotropin-releasing hormone (GnRH). To determine if this subnormal response is the result of lack of exposure of the pituitary gonadotroph cells to GnRH, five such men were given daily infusions of 500 microgram GnRH, for 7 days. A standard 250-microgram bolus test dose of GnRH was administered before and again immediately after the week of GnRH infusions. Five men who had severe hypogonadotropic hypogonadism as a result of presumed pituitary disease also received daily GnRH infusions for 1 week. The mean incremental LH responses (+/- SE) to GnRH of the men with presumed hypothalamic disease were 5.0 +/- 1.9 mIU/ml before and 56.9 mIU/ml after the week of infusions. The mean incremental LH responses of the men with presumed pituitary disease were 2.4 +/- 0.7 mIU/ml before and 3.7 +/- 2.9 mIU/ml after the week of infusions. These data suggest that the normal gonadotroph requires prolonged exposure to GnRH for LH responsiveness to become normal, but that the severely damaged gonadotroph cannot be stimulated to release LH normally even by the same prolonged stimulation with GnRH.

Penile Growth in Response to Human Chorionic Gonadotropin (hCG) Treatment in Patients with Idiopathic Hypogonadotrophic Hypogonadism

“…The central defect in most men with IHH is the loss of pulsatile secretion of GnRH from the hypothalamus 5-8. The objectives of therapy in adolescent and young adult males are to restore normal serum androgen levels to induce penile growth and puberty, and finally, to induce fertility.…”

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

“…Snyder et al [1979] evaluated 10 men with presumed pituitary or hypothalamic hypogonadism (all with testosterone <175 ng/dL) and infused GnRH over 4 hours daily for one week (21). Those men with pituitary etiologies (adenoma, hemochromatosis) of hypogonadism did not have robust increases in LH in response to prolonged GnRH pulses signifying inadequate gonadotroph function, whereas those with hypothalamic pathology (Kallman syndrome, sarcoidosis, or Hand-Schüller-Christian disease) had incremental increases in LH into the normal range (21). This phenomenon has been confirmed by others, and translated into therapeutic developments for both male and female infertility (22,23).…”

Secondary amenorrhea due to hydrocephalus treated with endoscopic ventriculocisternostomy

“…Although either GnRH testing or LH pulse analysis may be performed, pulsatile GnRH delivery may be necessary, as the pituitary does not always release LH in response to the first injection due to lack of priming. 26,34 It is possible that noncommunicating hydrocephalus leads to amenorrhea by dilation of the third ventricle and distention of the periventricular and medial basal regions of the hypothalamus, where one finds the ventromedial and arcuate nuclei in which GnRH producing parvocellular neurons are located. If progressive third ventricular dilation is responsible, perhaps GnRH release is disrupted only in the ventral hypothalamus, without disturbance of GnRH production elsewhere, leading to a relative GnRH deficiency.…”