Endocrine Abstracts

Introduction: Glucocorticoid resistance syndrome (GRS) is a rare familial or sporadic condition, caused by mutations in glucocorticoid receptor gene. It is characterised by generalised partial resistance of target tissues to cortisol action and compensatory elevation of ACTH with subsequent hypersecretion of cortisol, mineralocorticoids and androgens. Its clinical spectrum is broad and it may occur with high blood pressure (HBP) metabolic alcalosis, hypokalaemia and virilisation.

Case report: A 19-year-old black male was referred to Endocrinology department due to HBP diagnosed at 14 years old and elevated ACTH. He had delayed psycomotor development and epilepsy since childhood. There was no history of precocious puberty. His height, weight and blood pressure were 1.70 m, 52 kg and 139/95 mmHg, respectively. No signs or symptoms of deficiency or excess of glucocorticoids, hyperandrogenism or other causes of HBP were present. Complementary exams excluded adrenal enzymatic deficiency, primary aldosteronism, phaeochromocytoma and renovascular disease as aetiology of HBP. Pituitary–adrenal axis evaluation revealed: ACTH 158 pg/ml (ND-46), cortisol(s) 08/24 h 21.9/1.8 μg/dl, cortisol (u) 102.5 μg/24 h (20–90); low-dose dexamethasone suppression test (DST): cortisol(s) 19.8 μg/dl; high-dose DST: cortisol(s) <1.0 μg/dl. DNA analysis revealed a frameshift mutation c.2159_2160delAA, in heterozigoty in the NR3C1 gene, not yet described in the literature. Genetic study of relatives has not been done yet, since they live abroad.

Conclusions: The clinical spectrum of GRS is broad, ranging from severe to asymptomatic forms and the biochemical profile varies, depending on the severity of the defect in the signal transduction of glucorticoids. Persistent elevated urinary cortisol and ACTH with no clinical signs of hypercortisolism in this hypertensive young man led us to suspect of GRS. Diagnosis was confirmed by the finding of a not yet described mutation of NR3C1 gene.