Bone mass and mineral metabolism in Klinefelter's syndrome.

A reduced bone mineral density (BMD) is frequently observed in hypogonadal males; however, very little is known on bone and mineral metabolism in Klinefelter's syndrome (KS). In this study 32 XXY KS patients and 24 healthy age-matched male controls were examined. Serum total and free testosterone (TT and FT) were significantly lower in patients than in controls (TT in KS, 15.1 +/- 7.8 nmol/l; controls, 30.4 +/- 9.1; p < 0.001. FT in KS, 81.8 +/- 24.9 pmol/l; controls, 135.7 +/- 16.4; p < 0.001). 17 beta-Estradiol was slightly higher in KS patients (KS, 49.0 +/- 27.1 pg/ml; controls, 39.3 +/- 16.4 pg/ml), but the difference was not significant. BMD, measured at the spine (L2-4) and at the proximal epiphysis of the left femur, was similar in patients and in the control group (spine: KS, 1.016 +/- 0.142; controls, 1.085 +/- 0.144 g/cm2; p = not significant. Femoral neck: KS, 0.926 +/- 0.149; controls, 0.926 +/- 0.122 g/cm2; p = not significant). Bone GLA protein (BGP) was significantly higher in the KS group (12.7 +/- 4.8 vs 8.9 +/- 5.2 ng/ml; p < 0.02), while serum calcium, serum phosphate, calciotrophic hormones and the fasting urinary hydroxyproline/creatinine ratio (OHP/Creat) were similar in the two groups. A positive relationship between FT and both spine and femoral BMD was found in KS patients. Furthermore, OHP/Creat ratio was inversely related to BMD at the femur, and positively related to BGP in KS patients, but not in normal subjects. These findings suggest that (1) KS patients have normal bone mass, most probably because the hypogonadism is moderate; and (2) patients with lower bone mass appear to have higher bone turnover.

Osteoporosis and Klinefelter's syndrome.

OBJECTIVE: We wanted to measure forearm mineral density and bone-related biochemical variables in patients with Klinefelter's syndrome. DESIGN: Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age-matched normal male volunteers. PATIENTS: We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects. MEASUREMENTS: We measured forearm mineral density, forearm fat content, fat-corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio. RESULTS: Forearm mineral density was lower in the Klinefelter's group than in the control subjects (P less than 0.05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P less than 0.002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P less than 0.002). Serum dehydroepiandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r = 0.64, P less than 0.001), but not in the controls (r = 0.22, NS). Forearm mineral density and fat-corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r less than 0.63; P less than 0.01), but not in the control subjects (r less than 0.03, NS). CONCLUSIONS: Decreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased bone resorption.

Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter's syndrome.

Urinary total hydroxyproline excretion in patients with Turner's syndrome and Klinefelter's syndrome was studied. Among the patients with Turner's syndrome hydroxyproline excretion was relatively low in girls 11-14 years old and somewhat increased in 14-17 age groups. Above 17 years of age urinary total hydroxyproline excretion was significantly higher than in the control. In patients with Klinefelter's syndrome at the age below 11 and above 17 years normal hydroxyproline values were observed. In 3 sixteen-year-old boys with 47, XXY karyotype, excretion of hydroxyproline with urine was significantly lower than in the control. Relatively low values of total hydroxyproline in urine of 11-14 year-old girls with Turner's syndrome and decreased in boys with Klinefelter's syndrome result, most probably, from the absence of hormonal changes typical for the puberty. However, concentration of hydroxyproline in urine does not correlate with serum FSH and LH levels. It is not affected by the enhancement of changes in the bone system either. The presented data encourage further studies on the connective tissue biochemistry in the patients with numerical aberrations sex chromosomes.

[Urinary excretion of testosterone and androstenedione in hypogonadism in men]. / Vydelenie s mochoi testosterona i androstendiona pri gipogonadizme u muzhchin.

The authors present the results of determination of the testosterone and androstendion excretion in the patients with various forms of hypogonadism and in healthy men. Testosterone excretion was decreased in the patients with hypogonadism, against the background of normal or increased androstendion excretion whereas the degree of deviations of the testosterone/androstendion ratio depended on the clinical variant of hypogonadism. Thus, retarded or decreased accumulation of the enzymes in the testes responsible for the change from the "child" to the "mature" type of steroid biosynthesis could serve as a mechanism of hypogonadism occurrence, which should be taken into consideration in the elaboration of the methods of syndrome therapy of this type of pathology.

Systemic lupus erythematosus associated with klinefelter's syndrome.

Studies in estrogen metabolism were carried out in 2 males with systemic lupus erythematosus (SLE) who also had Klinefelter's syndrome. Although these studies revealed elevated levels of urinary estrogens in 1 patient, abnormalities of estradiol metabolism suggesting persistent estrogen stimulation were detected in both. This report notes an association between SLE and Klinefelter's syndrome and suggests that chronic estrogenic stimulation may be significant in the development of SLE in these 2 patients.

Evidence for a gonadotropin from nonpregnant subjects that has physical, immunological, and biological similarities to human chorionic gonadotropin.

Substances from urinary extracts of normal, nonpregnant subjects and human pituitary gonadotropin preparations were found to react similarly to human chorionic gonadotropin (hCG) in a radioimmunoassay system that is highly specific for hCG and without crossreactivity to human luteinizing hormone (hLH). The antiserum was produced in a rabbit immunized with a bovine albumin conjugate of the unique carboxyl-terminal peptide (residues 123-145) isolated from a tryptic digest of the reduced, S-carboxymethylated hCGbeta subunit. The antibody recognition site on the peptide was found to reside on the last 15 amino acid residues of the carboxyl-terminal peptide, as evidenced by the competitive binding activities against 125I-labeled hCG of a series of peptides chemically synthesized according to the carboxyl-terminal sequence of HCGbeta. In order to elucidate the nature of the crossreacting substance in urinary extracts, a human postmenopausal urinary preparation (Pergonal) and a kaolin-acetone extract of urine from a patient with Klinefelter's syndrome were subjected to gel chromatography on Sephadex G-100. The results indicate that fractions showing immunocrossreactivity with the antiserum to hCGbeta-carboxyl-terminal peptide coeluted with 125I-labeled hCG which was separated distinctly from hLH. The same fractions from this postmenopausal urinary gonadotropin preparation exhibited in vitro biological activity proportional to the immunocrossreactivity of the hCG-specific antiserum. Concentration of postmenopausal women's urine by acetone precipitation retained approximately five times more immunoreactivity per unit volume than kaolin-acetone extraction, when assayed with the antiserum to hCGbeta-carboxyl-terminal peptide.

[Gonadotropic hormone excretion in men with hypogonadism and its dynamics under the influence of exogenous testosterone]. / Ekskretsiia gonadotrophnykh gormonov pri gipogonadizme u muzchin i ee dinamika pod vliianiem ékzogennogo testosterone

The work is a clinico-laboratory study and and treats of the results of determination of gonadotropine excretion before and after the administration of testosterone to the patients with various forms of hypogonadism. The prevailing effect of testosterone on the excretion of the gonadotropic hormones could be blocking, stimulating or neutral depending on the clinical variant of hypogonadism. Thus, a change of sensitivity of the central link in the hypophysis-gonad system to the action of the peripheral hormones could apparently be of definite significance in the pathogenesis of hypogonadism; this should be taken into consideration in the elaboration of rational schemes of its therapy.

[Excretion of testosterone in men with various forms of hypogonadism]. / Ekskretsiia testosterona u muzhchin s razlichnymi formami gipogonadizma

A reduction of testosterone excretion in men with hypogonadism is reported in literature; however, the clinical peculiarity of its individual forms are not considered in these works. This paper treats of testosterone excretion in 43 patients with various forms of hypogonadism, of this number in 36 before and after a single testosterone-propionate loading. There was seen a reduction of testosterone excretion in hypogonadism. Secondary hypogonadism coursed against the background of a more marked insufficiency of testosterone excretion than the primary one. In a number of hypogonadism cases testosterone excretion remained unchanged and their clinical signs were caused by an inadequate realization of the androgenic effect. In hypogonadism an increase of the urinary excretion following its administration did not always correspond to the dose of the administered hormone, which could serve as one of the pathogenetic mechanisms of development of the disease.

Plasma testosterone in Klinefelter's syndrome: diurnal variation and response to ACTH and dexamethasone.

The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude. Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome.

Excretion of urinary testosterone in Klinefelter's syndrome.

The urinary testosterone excretion in 55 patients with Klinefelter's syndrome was determined by gas-chromatographic methods. The mean testosterone level in the group of Klinefelter patients was significantly decreased (15.7 mug/24 hrs) compared with the excretion by 30 normal men (44.1 mug/24 hrs). An age dependency of excretion levles was not obvious in chromatin-positive men when compared to healthy subjects. A correlation between testosterone excretion and configuration types seemed to be probable by reason of observations and statistical values. Average testosterone excretion increased with increasing normalization of body proportions. Gynecomastia was noticed in 56% of those examined. With increasing severity of gynecomastia the mean testosterone levels decreased. A correlation between beard and body hair, which was decreased in almost all subjects, and testosterone excreiton was not visible. With diminishing mean testosterone excretion an increase of osteoporosis seemed to be probable. A statistically significant difference was found when comparing patients who never had ejaculations with those who had regular libido and ejaculations. Klinefelter patients who had not succeeded in completing school or an occupational education showed a significantly decreased testosterone level as compared with others who had a profession.