Severe venous thromboembolism in a young man with Klinefelter's syndrome and heterozygosis for both G20210A prothrombin and factor V Leiden mutations.

Klinefelter's syndrome is the most common cause of primary testicular failure, resulting in impairment of both spermatogenesis and testosterone production. It is a chromosomal disorder characterized by small, firm testes, azoospermia, gynecomastia, varying degrees of eunuchoidism and testosterone deficiency with elevated gonadotropin plasma levels. In Klinefelter's syndrome there is an increase of certain systemic diseases including venous thromboembolism. An increased thromboembolic risk in hypogonadic men has been explained with hypofibrinolysis due to androgen deficiency. Only two cases have been reported about the association between Klinefelter's syndrome and well-known congenital or acquired thrombophilias. We report the case of a 39-year-old patient with Klinefelter's syndrome who underwent severe deep venous thrombosis with pulmonary embolism, in the absence of any circumstantial triggering event. Further examinations also showed a double heterozygosis for G20210A prothrombin and factor V Leiden mutations. This case suggests that the increased thromboembolic risk, reported in Klinefelter's syndrome, can be worsened by the co-existence of one or more well-known thrombophilic conditions, as shown by the relatively young age of the patient. More studies are needed to clearly understand the pathogenesis of venous thromboembolism in males affected by Klinefelter's syndrome.

Effect of glucose tolerance status on PAI-1 plasma levels in overweight and obese subjects.

OBJECTIVE: The aim of our study was to examine whether plasminogen activator inhibitor-1 (PAI-1) plasma levels varied as a function of differences in glucose tolerance status independently of body fatness, body-fat distribution, and insulin sensitivity. RESEARCH METHODS AND PROCEDURES: Plasma PAI-1 antigen levels, along with insulin resistance [measured by homeostatic model assessment (HOMA(IR))], central fat accumulation, body composition, blood pressure, and fasting concentrations of glucose, insulin, and lipids, were measured in 229 overweight and obese [body mass index (BMI) > or =25 kg/m(2)) subjects with normal glucose tolerance (NGT) and in 44 age- and BMI-matched subjects with impaired glucose tolerance (IGT). RESULTS: Plasma PAI-1 antigen levels were significantly higher in IGT than in NGT subjects. Log PAI-1 was positively correlated with BMI, HOMA(IR), and log insulin, and inversely associated with high-density lipoprotein-cholesterol both in IGT and in NGT individuals. On the other hand, log PAI-1 was positively correlated with waist circumference, fat mass (FM), fat-free mass, systolic and diastolic blood pressure, and log triglycerides only in the NGT group. After multivariate analyses, the strongest determinants of PAI-1 levels were BMI, FM, waist circumference, and high-density lipoprotein cholesterol in the NGT group and only HOMA(IR) in the IGT cohort. DISCUSSION: This study demonstrates that PAI-1 concentrations are higher in IGT than in NGT subjects. Furthermore, we suggest that the influences of total adiposity, central fat, and insulin resistance, main determinants of PAI-1 concentrations, are different according to the degree of glucose tolerance.