TY - JOUR
T1 - Primary cortisol resistance presenting as isosexual precocity
AU - Malchoff, Carl D.
AU - Javier, Emmanuel C.
AU - Malchoff, Diana M.
AU - Martin, Thomas
AU - Rogol, Alan
AU - Brandon, David
AU - Loriaux, D. Lynn
AU - Reardon, George E.
PY - 1990/2
Y1 - 1990/2
N2 - Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usuallydoes not produce clinical manifestations. This report describes primary cortisol resistance ina boy with isosexual precocity. A 6-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) testes. 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 <; 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, <;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-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 <; 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.
AB - Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usuallydoes not produce clinical manifestations. This report describes primary cortisol resistance ina boy with isosexual precocity. A 6-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) testes. 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 <; 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, <;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-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 <; 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.
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U2 - 10.1210/jcem-70-2-503
DO - 10.1210/jcem-70-2-503
M3 - Article
C2 - 2105334
AN - SCOPUS:0025015208
VL - 70
SP - 503
EP - 507
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -