Glucocorticoid Resistance Common in Premature Adrenarche and Polycystic Ovary Syndrome

New research indicates glucocorticoid resistance may be associated with states of premature adrenarche and polycystic ovary syndrome.

A small study, incorporating just 41 individuals with premature adrenarche or polycystic ovary syndrome, results indicate glucocorticoid resistance was present in more than half of all patients suffering from either of these conditions.

“The findings of our studies are significant as it gives a new insight into Premature Adrenarche, which was previously considered a benign condition,” wrote study investigators. “Based on the results of the present study, however, it may be more appropriate to reconsider Premature Adrenarche as an early indicator of an altered GC sensitivity that could help physicians to identify and prevent development of PCOS.”

To more accurately describe glucocorticoid sensitivity in patients with premature adrenarche and polycystic ovary syndrome, a team of endocrinologists from institutions across the US designed the current study to test their hypothesis that glucocorticoid sensitivity plays a role in the development in both the aforementioned diseases by increasing androgen synthesis. With the aim of testing their hypothesis that glucocorticoid sensitivity was altered in groups of premature adrenarche and polycystic ovary syndrome patients, investigators designed their study to compare glucocorticoid sensitivity in patients with either condition using A fluorescein labeled-dexamethasone (F-DEX)-mononuclear cell-binding assay.

In total, 14 patients with premature adrenarche and 27 patients with polycystic ovary syndrome were identified for inclusion in the study.

Of the 14 with premature adrenarche, 10 were girls and 4 were boys—the mean age of this group was 6.9±0.6 years. For inclusion in this group, findings of elevated dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEAS) and/or 17-hydroxypregnenolone levels before the age of 8 years with presence of body odor, axillary hair and/or pubic hair development. Exclusion criteria included precocious puberty, non-classical congenital adrenal hyperplasia (CAH), and exogenous hormonal exposure.

Of the 27 with polycystic ovary syndrome, the mean age was 17±2.5 years and polycystic ovary syndrome was defined using National Institutes of Health criteria. Inclusion criteria for this group included irregular periods with clinical signs of clinical hyperandrogenism including acne, hirsutism, and/or male pattern alopecia. Exclusion criteria included non-classical CAH and exogenous hormone exposure. Of note, investigators pointed out all patients included in this group had elevated testosterone levels.

For the purpose of the analysis, investigators created a glucocorticoid sensitivity index, which was calculated as the area under the cube of the F-DEX assay results. Patients were considered glucocorticoid resistant if their glucocorticoid sensitivity index was 264 or less and patients were considered glucocorticoid sensitive if the glucocorticoid sensitivity index was at 386 or greater.

Among patients with premature adrenarche, 8 of 14 patients were classified as glucocorticoid resistant (179.7±39.9), 4 were classified within the normal range of glucocorticoid sensitivity index (299.6±27.9), and 2 were classified as having glucocorticoid sensitivity (423.5±47.9).

Among patients with polycystic ovary syndrome, 18 of 27 patients were classified as glucocorticoid resistant (180.9±58.2), 8 were classified as within normal range (310±26.4), and 1 was classified as having an increased glucocorticoid sensitivity (395.4).

Additionally, among those with polycystic ovary syndrome classified as glucocorticoid resistant, cortisol levels were higher compared to polycystic ovary syndrome with normal glucocorticoid sensitivity index. Investigators also pointed out glucocorticoid sensitivity index correlated negatively with cortisol and testosterone in patients with polycystic ovary syndrome considered glucocorticoid resistant (P <.05).

This study, “Glucocorticoid Resistance in Premature Adrenarche and PCOS: From childhood to adulthood,” was published in the Journal of the Endocrine Society.