Fuqua John S, Rotenstein Deborah, Lee Peter A
Section of Pediatric Endocrinology and Diabetology, James Whitcomb Riley Hospital for Children, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Int J Pediatr Endocrinol. 2010;2010:712549. doi: 10.1155/2010/712549. Epub 2010 Mar 31.
Hydrocortisone has long been the treatment of choice for congenital adrenal hyperplasia (CAH). However, treatment with this medication remains problematic. Patients with 21-hydroxylase deficiency CAH have significant diurnal variation in the secretion of 17-hydroxyprogesterone (17OHP). When considering treatment strategies, this variation must be considered along with the pharmacokinetic and pharmacodynamic properties of exogenous glucocorticoids. Orally administered hydrocortisone is highly bioavailable, but it has a short time to maximum concentration (T(max)) and half life (T(1/2)). While prednisone has a somewhat longer T(max) and T(1/2), they remain relatively short. There have been several studies of the pharmacodynamics of hydrocortisone. We present data indicating that the maximum effect of hydrocortisone in CAH patients is seen 3 hours after a morning dose. After an evening dose, suppression of adrenal hormones continues until approximately 0500 the next day. In both situations, however, there is a large degree of intersubject variability. These data are consistent with earlier published studies. Use of alternate specimen types, possibly in conjunction with delayed release hydrocortisone preparations under development, may allow the practitioner to design a medication regimen that provides improved control of androgen secretion. Whatever dosing strategy is used, clinical judgment is required to ensure the best outcome.
长期以来，氢化可的松一直是先天性肾上腺皮质增生症（CAH）的首选治疗药物。然而，使用这种药物进行治疗仍存在问题。21-羟化酶缺乏型CAH患者的17-羟孕酮（17OHP）分泌存在显著的昼夜变化。在考虑治疗策略时，必须将这种变化与外源性糖皮质激素的药代动力学和药效学特性一并考虑。口服氢化可的松的生物利用度很高，但其达到最大浓度（T(max)）的时间和半衰期（T(1/2)）较短。虽然泼尼松的T(max)和T(1/2)略长一些，但仍然相对较短。已经有多项关于氢化可的松药效学的研究。我们提供的数据表明，CAH患者在早晨服药后3小时可看到氢化可的松的最大效果。在晚上服药后，肾上腺激素的抑制作用会持续到第二天大约05:00。然而，在这两种情况下，个体间都存在很大程度的变异性。这些数据与早期发表的研究一致。使用其他标本类型，可能与正在研发的缓释氢化可的松制剂联合使用，或许能让医生设计出一种能更好控制雄激素分泌的用药方案。无论采用何种给药策略，都需要临床判断以确保获得最佳疗效。
