Insulin resistance in patients with Klinefelter's syndrome and idiopathic gonadotropin deficiency

Patients with Klinefelter's syndrome (KS) have hypergonadotropic hypogonadism and have a higher incidence of diabetes mellitus. Patients with idiopathic gonadotropin deficiency (IGD) also have hypogonadism but have no proven impaired glucose metabolism. Because high serum testosterone concentrations are thought to correlate with insulin resistance, we assessed the relationship of testosterone concentration with insulin resistance in patients with KS or IGD and normal subjects. Seven patients with KS, six with IGD, and seven normal individuals (controls) were enrolled. Insulin resistance was evaluated by two methods: the total area under the curve (AUC) and the incremental AUC of serum insulin concentrations in response to a 75-g oral glucose load, and the insulin suppression test. KS patients had significantly higher follicle-stimulating hormone and luteinizing hormone concentrations than the normal controls, while IGD patients did not. The plasma testosterone concentrations were significantly lower in both KS and IGD groups than in controls. The incremental AUC and total AUC were higher in both KS and IGD patients than in normal subjects. The steady-state plasma glucose concentrations of the KS and IGD groups were significantly higher than that of the normal group, while the steady-state plasma insulin concentrations were similar in all three groups. After log transformation, the plasma testosterone concentration was negatively related to steady-state plasma glucose concentration in all three groups (r = -0.58, p = 0.019). In conclusion, insulin resistance was consistently noted in patients with KS and IGD. Plasma testosterone concentration is inversely related to insulin resistance.