Nocturnal Dexamethasone versus Hydrocortisone for the Treatment of Children with Congenital Adrenal Hyperplasia

Abstract

Classic congenital adrenal hyperplasia affects approximately 1 in 15,000 children. Current treatment strategies using multiple daily doses of hydrocortisone lead to suboptimal outcomes. We tested the hypothesis that nocturnal administration of dexamethasone will suppress the hypothalamic-pituitary-adrenal axis more effectively than standard hydrocortisone treatment by blocking the inherent diurnal secretion of ACTH. We performed a pilot study of five prepubertal patients comparing CAH control during two 24-hour hospitalizations, one on hydrocortisone and the other on dexamethasone. The patterns of adrenal suppression differed markedly between hydrocortisone and nocturnal dexamethasone, with significant suppression of the morning rise in ACTH, 17-hydroxyprogesterone, and androstenedione while on dexamethasone. On hydrocortisone therapy, there is a marked variation in ACTH and adrenal hormones depending on time of day and timing of hydrocortisone administration. Longer-term studies are needed to investigate the lowest effective dose and potential toxicity of nocturnal dexamethasone to determine its utility as a therapy for CAH.

Figure 1

Subject 1 blood ACTH (squares) and 17 hydroxyprogesterone (17OHP, triangles) over 23-hour period while on hydrocortisone (HC, black) or dexamethasone (Dex, brown). Androstenedione levels were less than assay at all time points on both regimens in this patient. To convert to SI units, multiply ACTH by 0.2222 (pmol/L), 17OHP by 30.2572 (pmol/L), and Androstenedione by 34.9162 (pmol/L).

Figure 2

Subject 2 blood ACTH, 17 hydroxyprogesterone and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figure 1.

Figure 3

Subject 3 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figures 1 and 2.

Figure 4

Subject 4 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figures 1 and 2.

Figure 5

Subject 5 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone. Subject 5 did not complete the dexamethasone admission due to technical difficulties. Abbreviations and symbols as in Figures 1 and 2.

Figure 6

Percent difference in area under the curve on dexamethasone versus hydrocortisone for ACTH, 17 hydroxyprogesterone, androstenedione, and urinary 17-ketosteroids (17-KS) for subjects 1–4. Subject 1 had androstenedione levels less than assay at all time points on both regimens and did not perform a urine collection for 17-ketosteroids.