Endocrine Abstracts

Background: Klinefelter syndrome (KS) is associated with hypergonadotropic hypogonadism as well as obesity, insulin resistance, and dyslipidemia. While impaired glucose metabolism has been described, adipose tissue lipolysis and free fatty acid (FFA) kinetics have not previously been directly examined in this population.

Aim: The purpose of this study was to evaluate FFA metabolism and adipose tissue insulin sensitivity in men with KS and to investigate if 6 months of TRT in males with KS would affect the regulation of FFA.

Methods: In this randomized, double-blinded, placebo-controlled, crossover study we recruited 13 patients and 13 healthy age-matched controls. Men with KS received 160 mg/day Andriol or placebo treatment for 6 months and were then crossed over. At the end of each treatment period, we applied a hyperinsulinemic euglycemic clamp with a palmitate tracer to quantify the regulation of lipolysis.

Results: The concentration of palmitate during clamp was 32.2 micromole/l for KS and 21.8 micromole/l for controls (P =0.0002). KS men had a significantly higher basal palmitate flux compared to controls (mean=194.2 and 121.2 micromole/ min, respectively; P =0.0264). The palmitate flux was significantly higher in KS compared with controls under clamp conditions (mean=79.5 and 33.3 micromole/min, respectively, P = 0.0044). No linear association was observed be-tween palmitate flux and energy expenditure in KS, in contrast to controls. Six months of TRT did not affect palmitate con-centration or flux in men with KS.

Conclusion: Reduced insulin suppression of lipolysis shows that KS men have an abnormal regulation of FFA and are insulin-resistant with respect to the regulation of lipolysis. The absence of a metabolic effect of TRT suggests that dysregulated lipid metabolism in KS is not solely attributable to hypogonadism. These findings support the presence of intrinsic alterations in adipose tissue metabolic regulation in this population.