Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.
Insulin resistance is associated with hyperandrogenic states. To determine the mechanisms by which androgen excess can affect insulin action, we studied insulin sensitivity in five nonobese hyperandrogenic women and six normal women. After oral glucose administration, the hyperandrogenic women had higher serum insulin concentrations than the normal women (P = 0.05). The mean cumulative peripheral serum insulin response in the hyperandrogenic women [79.6 +/- 30.8 (+/- SD) nmol/L.300 min] was significantly greater than that in the normal women (46.6 +/- 15.1 nmol/L.300 min; P less than 0.05). In the basal state and during hyperinsulinemic (20 mU/min.m2) euglycemic clamp studies serum insulin levels were similar in the two groups. Basal and insulin-mediated suppressions of hepatic glucose production determined from [3-3H]glucose specific activity were similar in the two groups. Peripheral glucose utilization was markedly diminished in the hyperandrogenic women compared to that in the normal women (27.8 +/- 6.7 vs 48.9 +/- 12.8 mumol/min.kg fat-free mass; P less than 0.01). We conclude that the insulin resistance in nonobese hyperandrogenic women is due to peripheral, but not hepatic, resistance to the action of insulin. This marked peripheral insulin resistance may result from the effects of hyperandrogenemia on skeletal muscle fiber morphology and metabolism.
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