Duration of Suppression of Adrenal Steroids after Glucocorticoid Administration

Glucocorticoids and mineralocorticoids are mainstays of the treatment of individuals with congenital adrenal hyperplasia (CAH). Several different glucocorticoids are in common use, including hydrocortisone, prednisone/prednisolone, and dexamethasone. Each of these agents has different pharmacokinetic and pharmacodynamic properties, and tailoring their dosing to provide individualized and appropriate control of adrenal androgen secretion remains a major clinical challenge. In this article, we will review the secretory patterns of adrenal steroids and discuss the pharmacokinetics of hydrocortisone and prednisolone. We will then present data from ourselves and others regarding the pharmacodynamics of hydrocortisone and review principles of treatment relating to steroid dosing.When assessing the efficacy of CAH treatment with different doses of glucocorticoids, one must take into account normal diurnal secretory patterns. It has long been known that cortisol production rates range between 5–9？mg/m2/day. This holds true for neonates, children, adolescents, and adults [1, 2]. The serum concentration of cortisol in normal individuals with typical sleep-wake patterns begins to rise at about 0400 and reaches its peak between 0700 and 0900 [3]. Over time, this diurnal variation is constant within individuals, although person-to-person variability is large [4]. Similarly, the variation of 17OHP secretion over a 24-hour period has long been recognized [5, 6]. Untreated subjects with CAH experience increasing serum concentrations of 17OHP between 2400 and 0400. After 1200, 17OHP levels spontaneously fall, although even at their nadir they remain much higher than normal [7, 8]. In treated patients with CAH, a similar pattern is observed. Charmandari et al. studied steroid secretory patterns in 36 treated children and adolescents with CAH [9]. They divided the 24-hour day into two periods: daytime, defined as 0400–1600, and nighttime, defined as 1600-0400. Mean 17OHP levels for 19