Klinefelter’s syndrome: a study of its hormonal plasma pattern

Abstract

Plasma testosterone (T), dihydrotestosterone (DHT), 17 beta-estradiol (E2), 17-hydroxyprogesterone (17-OHP), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 5-androstene-3 beta-17 beta-diol (A-diol) and cortisol (F) have been measured in a group of normal males and in a group of patients with Klinefelter's syndrome (KS) before and after hCG stimulation. Significantly lower baseline levels of T and DHT and significantly higher baseline levels of E2 were found in patients with KS. No significant differences were found between baseline levels of 17-OHP, delta, DHEA, DHEAS, A-diol, and F. After hCG stimulation between T, DHT, E2 and 17-OHP levels showed a significant increase in the two groups of subjects. The percentage variation of T and DHT, however, was much less important in Klinefeiter patients, while E2 and 17-OHP did not show a significantly different pattern from that of normal controls, hCG administration did not produce any significant variation of delta, DHEA, DHEAS, and F in the two groups of subjects, while A-diol levels increased significantly in normal subjects, but not in Klinefelter patients. Our data may be consistent with the hypothesis that testicular steroidogenesis in Klinefelter patients is impaired below the 21-C-steriod level not only at delta 4 but also at the delta 5 pathway.

The Metabolic Syndrome Is Frequent in Klinefelter’s Syndrome and Is Associated With Abdominal Obesity and Hypogonadism

“…The median total testosterone level was in the low-normal range but was substantially and significantly lower than the testosterone level in the control subjects, similar to previous findings (24), with reciprocally increased levels of LH and FSH (24,25), clearly illustrating that these Klinefelter's syndrome patients are hypogonadal. In contrast to some reports (25)(26)(27) but in accordance with others (24), SHBG was significantly lower and 17␤-estradiol was normal in Klinefelter's syndrome patients.…”

Klinefelter’s Syndrome: A Clinical and Therapeutical Update

“…2 ). Gynecomastia is present in 30-50% of patients and estradiol levels have been reported to be normal [Kamischke et al, 2003] or high [Forti et al, 1978]. However, as testosterone is often in the low-normal range the ratio estradiol/testosterone is increased in many patients in comparison to controls.…”

“…Male compensated hypogonadism is a not yet well-defined clinical disorder, since the mechanisms involved in the hypothalamic-pituitary-testicular axis functioning are more complicated and less sensitive than those involved in the hypothalamic-pituitary-thyroid axis [Tajar et al, 2010]. However, a reduced response of testosterone to hCG stimulation [Forti et al, 1978] and progressive impairment of Leydig cell function has been reported in adult Klinefelter patients [Gabrilove et al, 1979], thus suggesting a progressive shift towards overt hypogonadism with aging even in patients with normal testosterone concentrations.…”

Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography–tandem mass spectrometry

“…The hCG test, however, has never been standardized in KS patients and was variably based on the administration of 5000 IU of hCG as a single intramuscular dose (11); 5000 IU/day for 3 (12), 4 (13), or 5 days (12); 4000 IU/day for 4 (14) or 5 days (15); or 1500 IU/day for 3 days (16). In general, hCG stimulation was followed by an inconsistent rise of serum TS and/or other steroids, lower than in controls, generating the hypothesis of some enzymatic defects of testicular steroidogenesis of KS men (15,16,17,18,19,20). It should be noted that some early studies were performed even before radioimmunoassays for TS were in use and were based on competitive binding assays using sex hormone-binding globulin (SHBG) (14,18).…”

“…It should be noted that some early studies were performed even before radioimmunoassays for TS were in use and were based on competitive binding assays using sex hormone-binding globulin (SHBG) (14,18). In general, most studies hypothesized a specific deficiency in 17-20 lyase activity in KS (14,15,19). The current knowledge is that the 17-20 lyase activity of P450c17 is physiologically almost absent in normal Leydig and granulosa cells (5), and, thus, this hypothesis should be revisited as the mechanism of reduced TS secretion in KS men.…”