Dexamethasone Therapy of Congenital Adrenal Hyperplasia and the Myth of the "Growth Toxic" Glucocorticoid

The use of long-acting glucocorticoids in the treatment of individuals with Congenital Adrenal Hyperplasia (CAH) has been greeted with controversy [1]. A large part of this controversy rests on the mistaken assumption that prednisone is 5 times more potent than hydrocortisone and dexamethasone is 30 times more potent than hydrocortisone in suppressing adrenal androgen production [2]. These literature entrenched equivalencies are based on anti-inflammatory properties [2]. And when prednisone and hydrocortisone are used at 5- and 30-fold potencies relative to hydrocortisone, respectively, children will be overtreated [3, 4].As observed more than 50 years ago by Wilkins and coworkers, prednisone and dexamethasone are 15- and 80-fold more potent than hydrocortisone that in suppressing adrenal androgen production, respectively [5]. These relative dose equivalencies have been reaffirmed in clinical studies [6–9], and when prednisone and hydrocortisone are used at the higher potency equivalency ratios, children can be effectively treated with these long-acting glucocorticoids [6–8].The use of dexamethasone in the treatment of CAH was introduced in 1971 by Hayek et al. [10]. The authors noted "Elucidation of the circadian rhythm of ACTH release, and the demonstration that secretion as reflected by low 8 a.m. cortisol levels can be efficiently suppressed by a single 1-mg dose of dexamethasone, led us to investigate the efficacy of prolonged administration of the this compound once daily as an alternative to the conventional three daily dose in the treatment of patients with CAH". In detailed acute studies of four patients with CAH, daily administration of dexamethasone resulted in normalization of 17-ketoseteroid and pregnanetriol excretion (Figure 1). The dexamethasone doses used in these studies were 0.2 to 0.5？mg/m2.In the 1980s Hughes and colleagues at the University of Wales College of Medicine (Cardiff, UK) published an elegant series of publications relating to dexame