Endocrine Abstracts

Primary generalized glucocorticoid resistance or Chrousos syndrome is a rare disorder, which affects all tissues expressing the human glucocorticoid receptor. It has been defined by an absence of overt Cushing’s syndrome (CS) signs (no skin weakness, muscle atrophy, or osteoporosis) associated with biological hypercortisolism consisting of high urinary free cortisol (UFC) and an absence of negative feedback loop of cortisol on HPA, defined as 8-AM cortisol level >50 nmol/l after overnight 1 mg DXM suppression test. It is characterized by tissue insensitivity to glucocorticoids caused by genetic defects in the NR3C1 gene. To date, 31 NR3C1 loss-of-function mutations have been reported

Case Report: A 31-year-old woman was referred to our hospital to continue monitoring and treatment of ACTH-dependent CS. When she was 26-year-old an analysis was performed for a hormonal study prior to laser treatment for hirsutism, where elevated cortisol was evidenced, being referred to an outpatient clinic of endocrinology. An increased UFC was found of 2 times over the upper limit of normal (234 and 248 mg/dl), a disturbed 1-mg and 2-mg dexamethasone suppression test with a cortisol value of 8,14 and 14 µg/dl respectively and a high normal ACTH level of 136 pg/ml where evidenced. Pituitary imaging with magnetic resonance imaging (MRI) showed no pituitary adenoma. A bilateral petrosal sinus sampling was performed showing a lack of ACTH gradient. A whole-body CT was performed to evaluate tumors suggestive of ectopic ACTH secretion with no findings. In 2021 she arrived at our hospital. At physical examination her blood pressure was 110/70mmHg, her body mass index was 23.5 kg/m2. She hadn’t plethoric facial appearance, no central obesity, no muscle atrophy, no ecchymoses and no hirsutism. She had regular menses. No osteoporosis. Levels of UFC (243 mg/dl), ACTH (147pg/ml), DHEAS (675 mg/dl), androstenedione (6.9ng/ml), testosterone (0.59ng/ml) and 17OHprogesterone (3.90ng/ml) where similar than five years ago. Aldosterone concentration and ratio aldosterone/DRC were normal. A CT scan shows bilateral adrenal hyperplasia. With a suspected diagnosis of glucocorticoid resistance syndrome, we proposed a NR3C1 sequencing study in which no pathogenic variants were identified

Conclusion: In patients with biological hypercortisolism without signs and symptoms of CS we must think in a GC resistance syndrome. There had been several cases reports of patients with clinical and/or biochemical glucocorticoid resistance without alterations in glucocorticoid receptor gene NR3C1