Glucocorticoid Resistance in Premature Adrenarche and PCOS: From Childhood to Adulthood

Context: We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome (PCOS) by increasing androgen synthesis. Objective: To study glucocorticoid sensitivity in vitro in subjects with PA and PCOS. Patients and Methods: Fourteen subjects (10 girls, 4 boys, 6.9 +/- 0.6 years) with PA; 27 subjects with PCOS (17 +/- 2.5 years) and 31 healthy controls were enrolled in the study. All subjects and controls underwent GC sensitivity analysis in vitro using a fluorescein labeled-dexamethasone (F-DEX) assay. A GC sensitivity index (GCSI) was calculated as area under the curve of the F-DEX assay results. Subjects were classified as GC resistant if the GCSI <= 264 and GC sensitive if the GCSI >= 386. Results: In the PA group, 8 of 14 subjects were resistant with GCSI of 179.7 +/- 39.9, 4 were within the normal range with GCSI of 299.6 +/- 27.9, and 2 had increased GC sensitivity with GCSI of 423.5 +/- 47.9. In the PCOS group, 18 of 27 subjects were GC-resistant with GCSI of 180.9 +/- 58.2, 8 were within the normal range with GCSI of 310.7 +/- 26.4, and 1 had increased GCSI of 395.4. In the PCOS GC-resistant subgroup, cortisol was higher compared with PCOS with normal GCSI (P < 0.05). In the combined PCOS plus female control group, GCSI correlated negatively with cortisol and testosterone (P < 0.05). Conclusion: GC resistance was found in more than 50% of patients with PCOS and PA. The findings strongly suggest that GC resistance is associated with states of PA and PCOS. (C) Endocrine Society 2020.