ESPE Abstracts

Background: Treatment of a subset of Congenital Adrenal Hyperplasia (CAH) patients consists of glucocorticoids, such hydrocortisone and prednisone. Doses are titrated to achieve adequate levels of biochemical markers, namely 17-hydroxyprogesterone and androstenedione. When these biomarkers are abnormal, medication adherence is often considered. However, alterations in glucocorticoid sensitivity is rarely considered. We have created a fluorescein labeled dexamethasone(F-Dex) monocyte binding assay to measure glucocorticoids sensitivity that has been validated in multiple patient populations including PCOS and Nephrotic Syndrome. We propose to use the F-Dex monocyte binding assay to study glucocorticoid sensitivity in patients with CAH.

Objective: To use the F-Dex monocyte binding assay to study glucocorticoid sensitivity in patients with CAH.

Design/Methods: Samples were collected from patients with a diagnosis of CAH on steroid therapy. The samples were analyzed using a Fluorescein labeled dexamethasone (F-Dex) monocyte binding assay of collected monocytes. Glucocorticoid sensitivity index was calculated as the area under the curve of F-Dex-monocyte binding for control and subjects. Normal glucocorticoid sensitivity: GCSI: 266-285; glucocorticoid resistance: GCSI<265 and increased glucocorticoid sensitivity: GCSI>286.

Results: In our preliminary studies, we evaluated a patient with CAH that was treated with increasing doses of hydrocortisone up to 28 mg/m²/day. Despite the patient being on this high dose of hydrocortisone, the patient continued to have elevated 17 hydroxyprogesterone levels up to 2,139 ng/dL. Medication adherence was questioned in this patient. However, when the patient’s glucocorticoid sensitivity was measured with the F-Dex assay, the patient was found to be glucocorticoid resistant with a GCSI:258. Our group evaluated a second patient with CAH, who was also treated was treated with increasing doses of hydrocortisone up to 22 mg/m²/day. Despite the patient being on this higher dose of hydrocortisone, the patient continued to have elevated 17 hydroxyprogesterone levels up to 1770 ng/dL. Medication adherence was also questioned in this patient. The patient’s glucocorticoid sensitivity was measured via the F-Dex assay and the patient was found to be glucocorticoid resistant with a GCSI: 264.

Conclusion: Our preliminary results demonstrate that the cause of elevations in the biomarkers monitored in CAH can be due to alterations in glucocorticoid sensitivity. Examining glucocorticoid sensitivity in patients with CAH can lead to more precise glucocorticoid dosing that will allow better treatment, while avoiding side effects. This will be explored further with the examination of additional patients.