Background: Generalised glucocorticoid resistance (Chrousos syndrome) is a rare inherited disease characterized by tissue insensitivity to glucocorticoids and associated with defects in human glucocorticoid receptor (hGR) gene (NR3C1, 138040). Despite of elevated serum and urine cortisol the patients do not develop clinical picture of Cushing syndrome but present with hyperandrogenia and hypertension.
Case presentation: We present a case in which clinical features and laboratory results correspond to the Chrousos syndrome, but no mutations were identified in the GR gene. A 15-year-old girl was investigated because of hirsutism, acne and secondary amenorrhea. Physical examination revealed significant growth of hair on the lower abdomen and acne all over the body. She had normal blood pressure. Clinical signs of Cushing syndrome were not observed. Laboratory evaluation showed altered circadian plasma cortisol and ACTH rhytm (08:00 23.3 μg/dl and 71.5 pg/ml, 23:00 16.7 μg/dl and 62.8 pg/ml respectively), increased 24-h urinary free cortisol excretion (757 μg/day; n.r. 4.056 μg/day) and serum testosterone (144 ng/dl n.r. <775 ng/dl) and DHEA-S (368 μg/dl n.r. 44332) concentrations. A 1-mg overnight dexamethasone suppression test (DST) showed insufficient cortisol suppression (24 μg/dl), whereas high-dose DST (8 mg) revealed an appropriate suppression (6 μg/dl). According to this data, we suspected glucocorticoid resistance. Dexamethasone therapy was started in dose 0.5 mg per day with partial effect. 5 days after the initiation of treatment testosterone and DHEA-S level decreased (72 ng/dl and 184 μg/dl respectively). Three month later her menstrual cycle restored. Sequencing of the coding region of the NR3C1 gene did not reveal any mutations.
Conclusion: Severe hyperandrogenia in adolescents can caused by GC resistance. Other mechanisms of glucocorticoid resistance, than hGR gene mutations, remain to be elucidated.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology