Primary cortisol resistance presenting as isosexual precocity

Abstract

Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.