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Hypothalamic hamartoma is an important cause of precocious puberty in boys. Although the GnRH analogs are known to be effective therapy, there are few studies of the recovery of the pituitary-gonadal axis following long-term treatment. To this end, we studied 11 boys with HH after 8.8+/-3.2 yr (range, 4.0-12.6) of treatment with the GnRH agonist D-Trp6,Pro9,NEt-LHRH. The patients' levels of LH and FSH, testosterone, testis volume, and body mass index were compared with those of six normal boys in pubertal stage IV-V. We found that the patients' mean +/- SD peak GnRH-stimulated LH and FSH had returned to the normal range by 1 yr after stopping therapy. Whereas testosterone returned to normal levels by 1 yr, the patients' testis volume remained smaller than normal until 2 yr after therapy. Ultrasonography revealed diffuse, punctate, echogenic foci in the testicular parenchyma of two patients; these were first observed during GnRH agonist therapy and persisted unchanged after discontinuation of treatment. Neither of these two patients reported pain or testicular discomfort, no mass or irregularity was detected by manual examination in either patient at any time, and levels of beta-hCG and alpha1-fetoprotein were normal. By 4 yr after therapy, all patients had pubertal stage V pubic hair; their body mass index was not different from that of the normal boys at any time point. The dimensions of the patients' hamartomas did not change during or after therapy, and no patient reported new neurological symptoms or signs suggestive of an enlarging lesion at any time during or after discontinuation of treatment. Two families did report episodes of emotional lability and truancy as the patients reentered puberty after discontinuation of treatment.

Boys with Precocious Puberty Due to Hypothalamic Hamartoma: Reproductive Axis after Discontinuation of Gonadotropin-Releasing Hormone Analog Therapy