Background and Objective: Patients with Klinefelter Syndrome (KS) have increased cardiometabolic
risk however the pathogenesis is not clear. We investigated the presence of endothelial
dysfunction, insulin resistance and inflammation in an unconfounded population of KS.
Methods: A total of 32 patients with KS (mean age 21.59 ± 1.66 years) and 33 healthy control subjects
(mean age: 22.15 ± 1.03 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine
(ADMA), homeostatic model assessment of insulin resistance (HOMA-IR) index and highsensitivity
C-reactive protein (hs-CRP) levels were measured.
Results: The patients had higher Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH),
insulin, HOMA-IR and ADMA levels (p < 0.001 for all) and lower High Density Lipoprotein Cholesterol
(HDL-C) and total testosterone levels (p=0.002 and p<0.001, respectively), compared to the
healthy controls. Total testosterone levels were significantly negatively correlated to ADMA (r = -
0.479, p < 0,001), hs-CRP (r = -0.291, p = 0.034) and positively correlated to HDL-C (r = 0.429, p =
0.001) levels. The multivariate analysis has shown that total testosterone (β = -0.412, p = 0.001) and
TG (β = 0.332, p = 0.009) levels were the significant independent determinants of the plasma ADMA
Conclusion: The results of the present study show that endothelial dysfunction and insulin resistance
are prevalent even in the very young subjects with KS, who have no metabolic or cardiac problems at
present. Also, hypogonadism seems to play an important role for increased cardiometabolic risk in
patients with KS.