Klinefelter症候群における間脳-下垂体-睾丸系の内分泌学的研究

抄録

Twenty-five cases of Klinefelter's syndrome were extensively studied to clarify the mechanism of their hypothalamo-pituitary-testicualar function.
In the patients before treatment serum levels of follicle-stimulating hormone (FSH) and lutenizing hormone (LH), both measured by radioimmunoassay, were highly elevated compared with those in normal adult males. However, serum LH values in some cases were only slightly elevated above the upper limit of normal controls. Synthetic LH-releasing hormone (LH-RH, 100μg) administered im. provoked excessive increases of serum LH and FSH levels in these patients. Serum levels of testosterone (T) in these cases were significantly lower than those in normal adult men, but these values were scattered in a wide range and some were within the normal range. Human chorionic gonadotropin (hCG, 5000IU) administered im. for four days gave smaller increases of serum T levels in the cases with Klinefelter's syndrome than those observed in the control group.
Serum levels of gonadotropins were followed for three weeks after a single shot administration of a depot T preparation (100mg). The suppressive effect of the exogenous T load on serum gonadotropins was smaller in these cases than normal controls. Observation on the long-term substitution treatment by weekly im. injection of the depot T revealed that the serum levels of LH and FSH in these patients gradually decreased to the normal range or below in several weeks. However, when the injection interval was prolongecl to 2-3 weeks, the serum gonadotropin levels rebounded to higher levels than basal values. After the chronic T substitution therapy serum T levels were lowered and responses to hCG stimulation became smaller than before treatment. Also, serum gonadotropins were suppressed to a lesser degree by the same amount of exogenous depot T in chronically treated cases than in pre-treated patients.
It is concluded that in Klinefelter's syndrome alterations in the endocrine function of the hypothalamo-hypophyso-testicular axis are compatible with the nature of primary disorders of the seminiferous tubules causing secondary changes on the Leydig cell functions which are however variable among indiviual cases. The feedback sensitivity of the hypothalamo-pituitary system to peripheral T levels appears to be blunted in this syndrome and a highly excessive gonadotropin secretion continues for long duration after puberty. The doses of T substitution therapy, which is clinically effective inducing sufficient manifestation of androgenicity in this disease, are not effective enough to correct the abnormal hypothalamo-pituitary function.