Fig. 3. Cortisol and synthetic glucocorticoid profiles over 24 hours.

The physiological cortisol circadian rhythm has one peak in the morning at approximately 8.00 a.m. or upon awakening, with a gradual decline throughout the day¹¹². By contrast, in patients with congenital adrenal hyperplasia (CAH) receiving hydrocortisone three times daily (the glucocorticoid of choice in all children and select adults) results in three cortisol peaks approximately 90 minutes following each dose, followed by rapid declines to undetectable levels¹⁰⁸. Similarly, patients with CAH receiving once-daily dexamethasone or twice-daily prednisone have non-physiological glucocorticoid profiles⁴⁸. Failure to mimic the circadian cortisol profile contributes to management challenges and supraphysiological doses of glucocorticoid are typically needed to adequately suppress the adrenocorticotrophic hormone (ACTH)-mediated androgen excess of CAH. Data presented are from 24-hour serial sampling studies and reflect varied treatment practices. Data remain inconclusive regarding recommended dosing practices, including morning versus evening dose weighting. Data are expressed as geometric means. Data sources: healthy volunteers (n = 33, aged 17–57 years; dark blue line)¹¹²; patients with classic 21-hydroxylase deficiency CAH (n = 14, aged 17–55 years) on thrice-daily oral hydrocortisone tablet regimen (10 mg at 8.00 a.m., 5 mg at 3.00 p.m., 15 mg at 10.00 p.m.; yellow line)¹⁰⁸; patients with classic 21-hydroxylase deficiency CAH (n = 13) on an individualized dose thrice-daily oral hydrocortisone tablet regimen (8.00 a.m., 3.00 p.m. and 10.00 p.m.; orange line)²⁵; patients with CAH receiving once-daily dexamethasone (n = 4, dose range: 0.25–0.5 mg, median dose time: 10.00 p.m.; light blue line) or twice-daily prednisone (n = 11, dose range: 2–7.5 mg (morning), 2–5 mg (night), median dose administration times 8.00 a.m. and 9.00 p.m.; green line)⁴⁸.