A new form of insulin resistance with growth retardation, fatty liver, and hypogonadotropic hypogonadism.

A 17-year-old boy presented with growth retardation, marked hepatomegaly, and sexual infantilism. Elevated fasting serum insulin levels and a blunted hypoglycemic response to exogenous insulin (up to 0.35 unit/kg) demonstrated severe insulin resistance. Neither anti-insulin nor anti-insulin receptor antibodies were present. The molecular size of his circulating insulin and its binding to IM-9 lymphocytes was normal. Despite high circulating insulin values, both erythrocytes and cultured skin fibroblasts showed normal insulin binding capacity and affinity. Tissue responsiveness was examined by measuring the insulin-induced increase in 2-deoxyglucose uptake into fibroblasts. Although the basal glucose transport rate was slightly lower than that of controls, the insulin-induced increase was normal. However, the normal increase in thymidine incorporation in response to insulin was blunted, as were the thymidine incorporation responses to epidermal growth factor and fibroblast growth factor. These studies demonstrate the possible existence of a new form of post-insulin receptor defect as a cause of insulin resistance, but underscore the difficulty that exists in defining the exact nature of the defect in these disorders.