Background: Glucocorticoid resistance syndrome is a rare, familial or sporadic disease, caused by genetic mutations of the glucocorticoid receptor or at any other level of the signaling pathway. It is characterized by general, partial, target-tissue insensitivity to glucocorticoids, leading to activation of the hypothalamohypophysisadrenal axis resulting in compensatory increased levels of cortisol, but also increased concentrations of adrenal products with mineralocorticoid and androgenic activity by stimulating the adrenal with the excessive ACTH concentration. The clinical presentation is chronic fatigue, anxiety, symptoms and signs of mineralocorticoid excess (hypertension, hypokalemic alkalosis) and of androgen overproduction (acne, hirsutism, infertility, precocious puberty). The usual treatment consists in administration of high doses of Dexamethasone.
Case report: We present three cases (2F, 1M, 2128 years old) with glucocorticoid resistance syndrome. The two female patients presented severe hirsutism, menstrual irregularities and anxiety; all patients presented early-appeared hypertension and obesity. All patients had high plasma cortisol levels, normal to high ACTH levels, increased 24-hour urinary excretion of steroid-metabolites (17OHCS, 17CS), elevated androgen concentrations, normal circadian pattern of cortisol and resistance of HPA axis to dexamethasone suppression. All patients received treatment with ketoconazole 800 mg/day and were evaluated at 3 months, then every 6 months. All patients had a favorable clinical evolution with remission of hypertension, amelioration of hirsutism, weight-reduction and also normalized biological parameters. The male patient presented mild hepatocytolysis, as a side effect of the drug, that remitted after reducing the dose to 400 mg/day.
Conclusions: We consider that treatment with ketoconazole in glucocorticoid resistance syndrome is an efficient and safe alternative to therapy, with favorable effects on clinical and biological features of the disease.
25 - 29 Apr 2009
European Society of Endocrinology