ISOLATED COMBINED GROWTH-HORMONE AND GONADOTROPIN-DEFICIENCY DUE TO HYPOTHALAMIC DYSFUNCTION, ASSOCIATED WITH INSULIN-RESISTANCE

A 47-year-old woman was evaluated for congenital dwarfism, primary ame norrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and bioc hemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations un responsive to insulin or L-dopa administration. Prolactin, pituitary-a drenal and pituitary-thyroid axes were normal. Dynamic testing with Gn RH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone a nd gonadotrophin deficiency on the basis of a suprapituitary defect su ggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.