LBODP010 A Case of Glucocorticoid Resistance Syndrome

CASE PRESENTATION: A 55 yr old female presented with persistent mild elevation of cortisol for the previous 7 years. Four years prior to presentation, she was incidentally noted to have a small left sided adrenal nodule on CT scan of the abdomen. Biochemical evaluation of the nodule showed 24 hour urine cortisol of 176(0-50), morning cortisol of 36 ug/dl(6.2-19.4), ACTH 18 pg/ml(7.3-66.3), two out of three salivary samples with elevated cortisol. High dose dexamethasone suppressed ACTH to <1.1 from 13.8, cortisol from 30 to 3.3. She did not have signs and symptoms of Cushing's syndrome, mineralocorticoid excess nor androgen excess. Serum testosterone and DHEA were normal. DEXA revealed normal bone density. MRI brain demonstrated normal pituitary . She had no family history of pituitary or adrenal tumors nor endocrine syndromes. She underwent laparoscopic left adrenalectomy with pathology demonstrating benign adrenal adenoma, although the pathologist was unable to exclude nodular hyperplasia due to fragmented specimen. Elevation of 24 hour urine cortisol, serum cortisol and ACTH have persisted after surgery, without any clinical features of Cushing's. Gene sequencing with copy number analysis revealed heterozygous variant in the NR3C1 gene c.2239A>T(p. Ile747Phe), suspicious for autosomal dominant hereditary primary glucocorticoid resistance syndrome also known as Chrousos syndrome. DISCUSSION: Glucocorticoid resistance syndrome is rare, may be familial or sporadic, and is characterized by end organ insensitivity to glucocorticoids. Glucocorticoids are steroid hormones synthesized and secreted by adrenal cortex. The actions of glucocorticoids are mediated by the glucocorticoid receptor, which belongs to nuclear receptor family of ligand-dependent transcription factors. Affected individuals have elevations in circulating cortisol and ACTH, but no clinical evidence of hypercortisolism. Excess ACTH can result in increased mineralocorticoid and/or androgenic activity resulting in HTN and/or hypokalemic alkalosis and acne/hirsutism/infertility/male pattern hair loss. Asymptomatic, normotensive patients with primary glucocorticoid resistance do not require any treatment. Aim of treatment is to suppress excess ACTH to decrease mineralocorticoid and androgen effects. Treatment involves high doses of dexamethasone(1-3 mg/day), which activate the mutated and/or wild type hGR alpha and suppresses endogenous secretion of ACTH. CONCLUSION: Mutations in human GR gene impair one or more molecular mechanisms of glucocorticoid action affecting signal transduction and altering tissue sensitivity to these hormones. Recognition of this condition avoids unnecessary adrenal surgery and informs appropriate treatment and long term follow up of patients and family members. Presentation: No date and time listed