Klinefelter Syndrome Patients Research Articles

Effect of sex hormone treatment on circulating adiponectin and subforms in Turner and Klinefelter syndrome

Sex hormones have been shown to influence levels of adiponectin. Furthermore, testosterone has been shown to alter the subform distribution of adiponectin, whereas the effects of oestradiol are equivocal. We investigated the impact of sex hormone replacement therapy (HRT) on circulating adiponectin and its subforms, fasting lipids and measures of insulin sensitivity in Turner syndrome (TS) and Klinefelter syndrome (KS) respectively. We compared eight young TS patients on and off 2 months of HRT vs. eight age- and body mass index (BMI) matched healthy females as well as 19 untreated KS patients vs. 20 testosterone treated KS patients vs. 20 age and BMI matched healthy males. Total adiponectin and adiponectin subforms separated by fast protein liquid chromatography were measured using an in-house assay. In addition, fasting levels of insulin, glucose and homeostasis model assessment estimates were determined. In TS, total adiponectin levels were 10.5 +/- 3.1 (mean +/- SD) vs. 12.8 +/- 3.5 mg L(-1) (P = 0.02) and high molecular weight (HMW) adiponectin 5.8 +/- 2.7 and 6.8 +/- 1.9 mg L(-1) (P = 0.02) on and off HRT respectively. Irrespective of HRT, total adiponectin and HMW adiponectin were similar to control values. In KS, total adiponectin levels were 6.5 (3.0-24.2) (median and range) and 9.3 (4.3-14.3) mg L(-1) (P = NS) and HMW adiponectin was 2.5 (0.5-16.0) and 4.6 (1.3-8.6) mg L(-1) (P = NS) with and without testosterone treatment respectively, and similar to controls. Short time HRT suppressed HMW and total adiponectin levels in TS patients. Testosterone treatment in KS patients had no effect on these parameters. In both groups of patients either adiponectin or the HMW subform seems to play no greater role in reflecting or mediating insulin sensitivity. Our data indicates that in patients with TS and KS, sex hormones have different effects on circulating adiponectin and its HMW subform than previously reported in other sex hormone deficient patients and healthy subjects.

The azoospermia factor locus-c region was found to be related to Klinefelter syndrome in Turkish patients

We looked for a possible association between Klinefelter syndrome (KFS) and microdeletions in the Y chromosome in Turkish KFS patients. We examined the frequency of KFS in male patients with proven non-obstructive azoospermia and the types of Y chromosome microdeletions in these KFS patients. Fifty azoospermic patients and 50 fertile men were included in this study. KFS was found in 14 azoospermic patients. Y chromosome microdeletions were found in eight KFS patients. Azoospermia factor locus c (AZFc) was the most commonly deleted interval in KFS patients. All KFS patients had elevated plasma follicle-stimulating hormone and luteinizing hormone concentrations, but they had normal plasma testosterone concentrations. Testis biopsy of five samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions were found in the fertile group. We concluded that there could be an association between the AZFc region and KFS. Screening for this should be part of diagnostic work-up, particularly in those considering assisted reproduction.

Severe XIST hypomethylation clearly distinguishes (SRY+) 46,XX-maleness from Klinefelter syndrome

46,XX-maleness affects 1 in 20 000 live male newborns resulting in infertility and hypergonadotrophic hypogonadism. Although the phenotypes of XX-males have been well described, the molecular nature of the X chromosomes remains elusive. We assessed the X inactivation status by DNA methylation analysis of four informative loci and compared those to Klinefelter syndrome (KS) and Turner syndrome. Patient cohort consisted of ten sex-determining region of the Y (SRY+) XX-males, two (SRY-) XX-males, ten 47,XXY Klinefelter men, six 45,X Turner females and ten male and female control individuals each. Methylation analysis was carried out by bisulphite sequencing of DNA from peripheral blood lymphocytes analysing X-inactive-specific transcript (XIST), phosphoglycerate kinase 1 (PGK1), ferritin, heavy peptide-like 17 (FTHL17) and short stature homeobox (SHOX). XIST methylation was 18% in (SRY+) XX-males, and thus they were severely hypomethylated compared to (SRY-) XX-males (48%; P<0.01), Klinefelter men (44%; P<0.01) and female controls (47%; P<0.01). Turner females and male controls displayed a high degree of XIST methylation of 98 and 94% respectively. Methylation of PGK1, undergoing X inactivation, was not significantly reduced in (SRY+) XX-males compared to female controls in spite of severe XIST hypomethylation (51 vs 69%; P>0.05). FTHL17, escaping X inactivation, but undergoing cell-type-specific inactivation was similarly methylated in XX-males (89%), KS patients (87%) and female controls (90%). SHOX, an X inactivation escapee located in the pseudoautosomal region, displays similarly low degrees of methylation for XX-males (7%), KS patients (7%) and female controls (9%). XIST hypomethylation clearly distinguishes (SRY+) XX-males from Klinefelter men. It does not, however, impair appropriate epigenetic regulation of representative X-linked loci.

Genetic association between AZF region polymorphism and Klinefelter syndrome

Because of conflicting results about the association between azoospermic patients with Klinefelter syndrome (KFS) and azoospermia factor (AZF) polymorphism, and because nothing is known about the association of KFS with partial AZFc deletions, an association study was performed in Tunisian KFS patients. A total of 29 azoospermic patients and 13 fertile men were enrolled in this study. The classical microdeletions were found in six out of nine KFS patients (67%). Gr/Gr deletions and b2/b3 deletions are partial AZFc deletions. One KFS patient without classical microdeletions had a gr/gr deletion. This deletion (gr/gr) was observed in four out of 18 azoospermic patients without chromosomal abnormalities. In addition, two b2/b3 and one AZFc deletion were identified in this group. All KFS patients had elevated plasma FSH and LH concentrations, but normal plasma testosterone concentration. The testis biopsy of three samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions or partial AZFc deletions were found in the fertile group. It is concluded that in the patient population KFS patients may harbour Y microdeletions, and screening for these should be part of the diagnostic work-up, particularly in those considering assisted reproductive techniques. However, partial AZFc deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KFS subjects.

Probability of taking home baby in cases of non-mosaic Klinefelter's syndrome based on the experience of 60 patients

OBJECTIVE: In this study, we aimed to assess the efficacy of testicular sperm extraction (TESE) combined with ICSI as a therapeutic option for azoospermic Klinefelter's syndrome (KS) patients. DESIGN: Retrospective analysis of clinical outcome in 60 KS patients. MATERIALS AND METHODS: A total of 60 azoospermic non-mosaic KS patients visited the clinic from 1999 to 2008 was involved in the study. On all the patients with written informed consent, TESE was attempted. Multiple testicular biopsy method was utilized until the end of 2004 (26 cases) while micro-dissection TESE was exploited (34 cases) thereafter. When at least one viable spermatozoon was obtained, ICSI was performed with fresh, frozen-thawed or re-frozen re-thawed testicular spermatozoa. RESULTS: The rate of successful sperm retrieval was 45.0% (27/60). With multiple testicular biopsy method the sperm recovery rate was 34.6% (9/26) while it was 52.9% (18/34) with micro-dissection technique. Among 27 patients with viable spermatozoa, 24 cases underwent total of 35 ICSI treatment cycles, 7 with fresh, 27 with frozen-thawed, and 1 with re-frozen re-thawed testicular spermatozoa. In 2 cases no embryos were available for transfer. Consequently 30 fresh and 9 frozen-thawed embryo transfers were performed, resulting with 19 clinical pregnancies and 15 live births so far. Overall 22 newborn (11 boys and 11 girls) were obtained following TESE-ICSI, with 1 case being still ongoing at the moment of the preparation of this abstract. CONCLUSIONS: Although statistically not significant (P = 0.064), there was a trend of higher sperm recovery rate in micro-dissection TESE than conventional method. This study with a relatively large number of cases, demonstrates that TESE-ICSI is an effective treatment option for non-mosaic KS patients with thorough genetic counseling. It can be estimated that about a half of cases sperm can be retrieved with over 60% of live birth rate, thereby, approximately 30% of take home baby rate is expected in first seen azoospermic KS patients.

Serious Venous Thromboembolism, Heterozygous Factor V Leiden and Prothrombin G20210A Mutations in a Patient with Klinefelter Syndrome and Type 2 Diabetes

Klinefelter's syndrome (KS) is a common cause of man infertility characterized by small testes, gynecomastia and hypogonadism. Deep vein thrombosis and thomboembolic events are frequent in these patients. Hormone imbalance and co-existent mutations in the coagulation system may be the primary factors in this hypercoagulable state. The increased thromboembolic risk in hypogonadic men has been explained by hypofibrinolysis due to androgen deficiency. Regarding the association between KS and congenital and acquired thrombophilias, to date, only three cases have been. Here, we present the youngest KS case with pulmonary thromboembolism with the heterozygous mutations in factor V Leiden and prothrombin genes, as detected by further tests. He had the previous diagnosis of diabetes mellitus and body mass index was 30 kg/m(2). Our report discusses the prothrombotic state in KS patients, with other possible causes for the young presentation and the importance of necessary tests in emergency service admissions with embolism.

Fertility in a i(Xq) Klinefelter patient: importance of XIST expression level determined by qRT-PCR in ruling out Klinefelter cryptic mosaicism as cause of oligozoospermia

The presence of an isochromosome Xq in Klinefelter syndrome (KS) is an apparently rare condition. In all cases reported so far, patients showed the classic phenotype. We here describe a case of isochromosome Xq [47,X,i(Xq),Y] in a non-mosaic KS patient. The patient exhibited a normal androgenized phenotype, normal testes and normal cognitive abilities. Semen analysis revealed a medium oligozoospermia (5 x 10(6) spermatozoa/ml). After the patient underwent intracytoplasmic sperm injection, he generated two cytogenetically healthy normal females. Fluorescence in situ hybridization analysis showed the presence of a dicentric Xq chromosome that did not show the presence of residual Xp arm up to the 57,820,478 bp position (Xp 1.1) of X chromosome sequence. Preferential inactivation of Xq isochromosome was demonstrated by bromodeoxyuridine replication analysis and transcriptional silencing by DNA methylation at the HUMARA locus. Furthermore, we demonstrated by quantitative RT-PCR an active XIST RNA expression in blood lymphocytes from Klinefelter patients, comparable to that observed in control females and over 30,000-fold greater than in control males. In conclusion, this qRT-PCR approach could be useful for screening of prepuberty males and for diagnosis or exclusion of cryptic Klinefelter mosaics.

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism

Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. Cross-sectional study. Out-patient clinic. We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. The long axis function was significantly reduced in patients with KS (peak systolic velocities 4.4 +/- 1.3 vs. 5.3 +/- 1.0 cm/s, P < 0.01 and strain rate -1.3 +/- 0.3 vs.-1.6 +/- 0.3 s(-1), P < 0.01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = -0.72, P < 0.01) and free testosterone (r = 0.63, P < 0.01), but uncorrelated to plasma glucose, insulin and HOMA-index. Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.

Severe Arterial Thrombophilia Associated With a Homozygous MTHFR Gene Mutation (A1298C) in a Young Man With Klinefelter Syndrome

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It may be associated with an increased risk for venous thrombosis and thromboembolism, which is partially explained by hypofibrinolysis due to androgen deficiency. Additional genetic or acquired thrombophilic states have been shown in KS patients complicated with venous thrombosis as isolated case reports. Arterial thrombotic events had not been previously reported in KS. In this study, a young man with KS who developed acute arterial thrombosis during testosterone replacement therapy is presented. He was homozygous for the A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene.

Metabolic Syndrome in Men with Klinefelter's Syndrome

To investigate the metabolic syndrome and sex hormones in patients with Klinefelter's syndrome (KFS), 46XY men with nonobstructive azoospermia (NOA), and an age-matched obstructive azoospermia (OA) group. We examined 60 patients with KFS, 60 46XY male patients with NOA, and 50 patients with OA. Height, weight, waist circumference, and blood pressure were examined. Fasting blood samples were analyzed for sex hormones, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, and plasma glucose. Height, weight, and waist circumferences were significantly greater in KFS patients compared with NOA and OA patients. Low-density lipoprotein cholesterol of KFS patients (132.9 +/- 29.4 mg/dL) was significantly increased compared with NOA (117.0 +/- 27.8 mg/dL) and OA patients (106.1 +/- 27.9 mg/dL) (P <0.05 and P <0.01). High-density lipoprotein cholesterol was significantly decreased in KFS patients (50.1 +/- 15.9 mg/dL) compared with NOA (58.7 +/- 11.7 mg/dL) and OA patients (59.5 +/- 17.9 mg/dL) (both P <0.05). Total cholesterol, triglycerides, and fasting glucose were not significantly different among the three groups. The differences between KFS and NOA, KFS and OA, and NOA and OA were all significant (P <0.01, P <0.001, and P <0.01, respectively) in terms of follicle-stimulating hormone, luteinizing hormone, and free testosterone level. Hypogonadism in KFS may cause an unfavorable change in body composition and the metabolic syndrome.

Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm

The aim of this study was to investigate the feasibility of using frozen-thawed testicular sperm as well as the timing of testicular sperm extraction (TESE) in patients with non-mosaic Klinefelter syndrome. Intracytoplasmic sperm injection (ICSI) was performed in six of 17 (35%) patients whose sperm was recovered by TESE. Multiple biopsies of both testes were performed on the day of oocyte retrieval in all but one of the six patients. Seven pregnancies and deliveries were achieved in five couples, and one couple was unsuccessful. Five pregnancies were achieved using fresh motile sperm, and two were achieved using frozen-thawed sperm. Sperm cryopreservation was not possible in one of the five couples because of the small number of recovered sperm, and possible in four other couples for subsequent ICSI. One woman whose husband had TESE performed prior to ovarian stimulation did not become pregnant. This may be due to the attainment of only a few immotile sperm following the frozen-thawed procedure. The outcome of ICSI using fresh or frozen-thawed testicular sperm in patients with non-mosaic Klinefelter syndrome was identical; however, TESE should be performed on the day of oocyte retrieval until such time as a procedure with a higher sperm yield from TESE is available. Moreover, an improved recovery procedure after cryopreservation-thawing of a single spermatozoon must be developed.

O-249: The risk of intracytoplasmic sperm/spermatid injection for non-mosaic Klinefelter syndrome patients

Previously published results of sperm analysis using multicolor FISH in XXY indicated the presence, in most cases, of an increase in the proportion of abnormal XY and XX spermatozoa in XXY males. It has been reported that the sex chromosome abnormality incidence rate for ICSI children increased when Klinefelter syndrome patient sperm had been used. We conducted this study to investigate the mechanism of germ-cell mosaics.

Klinefelter syndrome and mediastinal germ cell tumors

Precocious puberty is not a typical manifestation of patients with Klinefelter syndrome (KS). However, there is an increased incidence of mediastinal germ cell tumors (M-GCT) in KS, whereas the discussion of a generally higher tumor risk in this condition is still controversial. A rare subgroup of KS patients consists of prepubertal children with precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs. We present clinical data on a boy with KS and sexual precocity, and summarize the published data on 12 boys with KS out of 54 cases of KS and M-GCT. an 8.5-year-old boy presented with signs of precocious puberty. Laboratory analyses (suppressed gonadotropins, elevated testosterone) and thoracic CT demonstrated a beta-human chorionic gonadotropin (beta-hCG) and alpha(1)-feto protein (alpha-FP) secreting mediastinal tumor. Histological analysis showed a mixed germ cell tumor comprising choriocarcinoma (CH), embryonal carcinoma (EC), mature teratoma (MT), and yolk sac tumor (YS). He was successfully treated by surgery and adjuvant chemotherapy. Epianalysis of published cases: all KS patients (n = 12), age 4-9 years, presented with precocious sexual development (PP), whereas the older ones showed thorax-associated symptoms, mainly chest pain, dyspnea, and cough. The histological distribution was also age-dependent with mixed germ cell tumors predominantly in younger patients. Thus, M-GCTs are strongly associated with precocious puberty in young boys with KS. Therefore, a karyotype analysis should be included in the clinical work-up of boys with precocious puberty and M-GCT. There is still no convincing explanation for the association of M-GCTs and KS.

Evaluation of event-related potentials in Klinefelter syndrome and idiopathic hypogonadotrophic hypogonadism.

Many studies have evaluated patients with idiopathic hypogonadothropic hypogonadotropism (IHH), but few of these studies utilize event-related potentials (P300). To assess the cognitive functions of hypergonadotropic vs. hypogonadotropic patients. The study group consisted of 41 untreated IHH patients, 32 untreated Klinefelter syndrome (KS) patients, and 30 healthy control subjects. In this study, the latency and amplitude of P300 was evaluated in 41 untreated IHH and 32 untreated KS patients and compared to healthy control subjects (average age: 30 years). Also evaluated were the patients' hormone levels. In this study, the amplitude of P300 was found to be reduced, and the latency prolonged in IHH patients in comparison to KS patients and control subjects. In KS patients, there was no difference in latency of P300, but the amplitude was reduced when compared with the control group. Cognitive dysfunction in patients with hypogonadotropism is related to androgen hormone levels. This deficiency can affect development of the central nervous system (CNS), causing defects of CNS to varying degrees during the perinatal period. Androgen deficiency is considered to exert its effects during the period of cognitive ability development, manifest in IHH patients but not KS patients.

Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter’s syndrome

To determine factors affecting successful sperm retrieval by testicular sperm extraction in patients with nonmosaic Klinefelter's syndrome. Medical record analysis for nonmosaic Klinefelter's syndrome patients who underwent testicular sperm extraction. Three university-based tertiary centers. Fifty-one patients with nonobstructive azoospermia related to nonmosaic Klinefelter's syndrome. Testicular sperm extraction. Correlation of patient characteristics; serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T); as well as testicular volume with success in testicular sperm extraction. We succeeded in obtaining spermatozoa in 26 patients and failed in 25. Levels of LH, FSH, and T and testicular volume did not differ between patient groups defined by success and failure. Median ages for successful and failed testicular sperm extraction were 31 and 38 years, respectively (statistically significant difference). When we analyzed success rates of testicular sperm extraction between two patient groups (<35 and > or =35 years old), the percentage of successful recovery of spermatozoa decreased after the age of 35 years (statistically significant difference). Testicular sperm extraction should be recommended before the critical age of 35 years.

Sperm aneuploidy in fathers of Klinefelter’s syndrome offspring assessed by multicolour fluorescent in situ hybridization using probes for chromosomes 6, 13, 18, 21, 22, X and Y

It is still unclear if a recurrence risk would exist in fathers of an aneuploid offspring of paternal origin. We have studied disomy frequencies in spermatozoa from fathers having Klinefelter syndrome (KS) offspring or miscarriages. The effect of paternal age on sperm disomy percentages is also analysed. Parental origin of 17 KS patients was carried out by amplification of X chromosome polymorphisms. Spermatozoa from their fathers were studied by multicolour fluorescent in situ hybridisation (FISH) using probes for chromosomes 6, 13, 18, 21, 22, X and Y. In 53% of KS cases studied the additional X chromosome was of paternal origin. The paternally transmitted KS group of fathers showed significantly higher frequencies for XY disomy sperm as compared to fathers of the maternal-origin group. A correlation between paternal age and XY disomy frequencies was only found in the paternally derived cases. In contrast, similar disomy frequencies for all autosomes analysed were found in both groups of fathers. XY disomy frequencies increase with advancing paternal age only in fathers with paternally inherited KS offspring.

Age as a Limiting Factor for Successful Sperm Retrieval in Nonmosaic Klinefelter Syndrome

Intracytoplasmic sperm injection (ICSI) now permits fertilization of eggs using very small numbers of spermatozoa. Improvements in testicular sperm extraction (TESE) techniques have expanded indications from oligozoospermia to nonobstructive azoospermia. Klinefelter syndrome, which accounts for 5% of the latter cases, is characterized by sterility caused by lack of spermatogenesis. Isolated foci of spermatogenesis have been found in involved testes, explaining the rare cases of sperm production with appearance in the ejaculate. Several institutions perform TESE using either ordinary testicular biopsy techniques or meticulous microdissection to retrieve spermatozoa for ICSI. The reported success rate for TESE in patients with Klinefelter syndrome is 56%, but no predictive factors have been identified given the paucity of cases in each report. We analyzed results of TESE to elucidate success determinants for TESE in patients with Klinefelter syndrome. Retrospective analysis of microdissection TESE in nonmosaic Klinefelter syndrome patients. A collaborative study with three institutions. Eighty-four patients with nonobstructive azoospermia related to nonmosaic Klinefelter syndrome underwent TESE. To determine factors affecting successful sperm retrieval by TESE in patients with nonmosaic Klinefelter syndrome medical record were analyzed retrospectively. Correlations of patient characteristics, serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T), as well as testicular volume with success in testicular sperm extraction were investigated. We succeeded in obtaining spermatozoa in 51 patients and failed in 33. LH, FSH, T, and testicular volume did not differ between patient groups defined by success and failure. Median ages for successful and failed TESE were 32.6 and 37.1, respectively (p<0.001). When we analyzed success rates of testicular sperm extraction for 5-year age brackets, the ratio of successful recovery of spermatozoa to failure decreased beyond 35 years. Testicular sperm extraction should be recommended before the critical age of 35 in nonmosaic Klinefelter syndrome patients.

Mosaic status in lymphocytes of infertile men with or without Klinefelter syndrome

Gonosomal aneuploidies such as Klinefelter syndrome (47,XXY) are the most frequent chromosomal aberration in infertile men. Normally the chromosomal status of patients is detected by karyotyping of up to 20 metaphase spreads of lymphocyte nuclei, whereby low grade mosaicism may be overlooked. To test whether Klinefelter patients with 47,XXY karyotype or infertile men with 46,XY karyotype represent gonosomal mosaicisms, we performed meta- and interphase fluorescence in situ hybridization (FISH) on 45 men. A total of 400 interphase and 40 metaphase lymphocyte nuclei per patient were scored after hybridization with DNA probes specific for chromosomes X and Y, and chromosome 9 as a control. On the basis of conventional karyotype, hormone levels and clinical appearance, patients were subdivided into 18 Klinefelter syndrome patients with 47,XXY (group I), 11 Klinefelter syndrome-like patients with normal karyotype, 46,XY (group II) and six non-Klinefelter-like infertile patients with normal 46,XY karyotype (group III). Ten normal men (group IV) served as controls. Testicular volume in the Klinefelter group I was smaller compared with group II (P = 0.016), group III (P < 0.001) and group IV (P < 0.001). In addition, testicular volumes in group II were lower compared with group III and group IV (P < 0.004). No significant differences between the aneuploidy rate analysed by FISH in interphase nuclei and metaphases were found in either single patients or groups. Patients with Klinefelter syndrome, 47,XXY (group I) or with symptoms similar to those in Klinefelter patients 46,XY (group II) showed a similar aneuploidy rate (group I 7.1 +/- 4.0% and group II 4.6 +/- 3.4%) and two 47,XXY patients with a high prevalence for normal 46,XY lymphocytes had sperm in their ejaculate. However, in general, no correlations between FISH mosaic status and serum hormone parameters, nor with ejaculate parameters were found. The results suggest that 47,XXY patients with an increased incidence of XY cells (average of 4.2 +/- 2.3) may have a higher probability of germ cells as we found sperm only in the ejaculate of Klinefelter syndrome patients with mosaic 46,XY cells (6.0 and 7.0%). On the other hand, 46,XY patients with mosaic sex chromosome aneuploidies detected by FISH analysis more often show symptoms of hypogonadism phenotypically resembling Klinefelter syndrome.

Evaluation of Insulin Sensitivity in Patients with Klinefelter's Syndrome: A Hyperinsulinemic Euglycemic Clamp Study

Patients with Klinefelter's syndrome have a higher incidence of diabetes mellitus and the percentage of insulin resistance was reported to be high in these patients. However, little is known about the insulin sensitivity assessed by the hyperinsulinemic euglycemic clamp in these patients. In the present study, subjects included 13 newly diagnosed patients with Klinefelter's syndrome, and 9 age- and body mass index-matched healthy males. The hyperinsulinemic euglycemic clamp was performed in all patients and controls. Insulin resistance was present in five (38.5%) patients with Klinefelter's syndrome. Compared with control subjects, patients with Klinefelter's syndrome had elevated plasma concentrations of fasting insulin, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin, whereas they had reduced plasma free testosterone and total testosterone concentrations. The multivariate linear regression analysis showed that fasting glucose, fasting insulin, free testosterone, and total testosterone were independently associated with M-value. In conclusion, the present study by using hyperinsulinemic euglycemic clamp indicates the high prevalence of insulin resistance in Klinefelter's syndrome patients. However, these patients did not have reduced mean M-values compared with the controls, although their plasma insulin levels were significantly elevated. It is possible that hyperinsulinemia may be the primary metabolic abnormality rather than insulin resistance.

Effect of supraphysiologic doses of testosterone on fasting plasma total homocysteine concentrations in men with Klinefelter's syndrome

Objective To examine the effect of supraphysiologic doses of testosterone (T) on plasma total homocysteine (tHcy) concentrations in patients with Klinefelter's syndrome (KS). Design Prospective clinical study. Setting University hospital. Patient(s) Thirty-two newly diagnosed male patients with KS, and 20 healthy, volunteer controls matched by age and body mass index. Intervention(s) Testosterone was administered IM every 2 weeks for 6 months. Initially, pretreatment fasting blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 7 days after the last injection. Main outcome measure(s) Plasma total homocysteine. Result(s) The KS patients had lower tHcy levels than the controls. However, plasma fasting tHcy concentrations increased in a statistically significant manner after 6 months of treatment. As compared with the levels among controls, pretreatment levels of the serum creatinine, hemoglobin, and hematocrit were significantly lower, and increased in a statistically significant way following treatment. Posttreatment levels of total cholesterol were statistically significantly higher than the baseline. The pretreatment folate and cobalamin levels also were statistically significantly higher in patients when compared with controls, and decreased significantly after treatment. The linear regression analysis showed that only creatinine, cobalamin, and folate were independently associated with plasma tHcy levels in patients before and after treatment. Conclusion(s) The patients with KS showed lower tHcy concentrations than healthy, age-matched male controls. Testosterone treatment increased plasma tHcy levels.