Nella Aikaterini A, Mallappa Ashwini, Perritt Ashley F, Gounden Verena, Kumar Parag, Sinaii Ninet, Daley Lori-Ann, Ling Alexander, Liu Chia-Ying, Soldin Steven J, Merke Deborah P
Eunice Kennedy Shriver National Institute of Child Health and Human Development (A.A.N. D.P.M.), National Institutes of Health, Bethesda, Maryland 20892; and National Institutes of Health Clinical Center (A.A.N., A.M., A.F.P., V.G., P.K., N.S., L.-A.D., A.L., C.-Y.L., S.J.S., D.P.M.), Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 2016 Dec;101(12):4690-4698. doi: 10.1210/jc.2016-1916. Epub 2016 Sep 28.
Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction.
This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH.
Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires.
The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured.
CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue.
CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.
经典型先天性肾上腺皮质增生症（CAH）的管理仍然具有挑战性，因为通常需要超生理剂量的糖皮质激素来最佳地抑制促肾上腺皮质激素（ACTH）驱动的肾上腺雄激素过度分泌。
本研究旨在通过持续皮下输注氢化可的松（CSHI）来模拟生理皮质醇分泌，并评估CSHI在难治性CAH患者中的安全性和有效性。
8名成年经典型CAH患者参与了一项单中心开放标签的I-II期研究，比较CSHI与传统口服糖皮质激素治疗。所有患者在研究开始时肾上腺类固醇水平升高且有一种或多种合并症。在基线接受传统治疗时以及CSHI治疗6个月后的评估包括：24小时激素采样、代谢和放射学评估、健康相关生活质量（HRQoL）和疲劳问卷。
测量CSHI模拟生理皮质醇分泌的能力以及07:00时17-羟孕酮（17-OHP）≤1200 ng/dL的患者百分比。
CSHI模拟了生理皮质醇分泌。与基线相比，CSHI治疗6个月导致07:00时和24小时曲线下面积的17-OHP、雄烯二酮、ACTH和孕酮降低，骨钙素、C-末端肽和瘦体重增加，HRQoL（以及SF-36活力评分）和疲劳得到改善。三名闭经女性中有一名恢复月经。一名男性的睾丸肾上腺残余组织减少。
CSHI是一种安全且耐受性良好的皮质醇替代方式，可有效模拟传统治疗控制不佳的经典型CAH患者的生理皮质醇分泌。肾上腺类固醇控制的改善以及对HRQoL的积极影响表明，CSHI应被视为经典型CAH的一种治疗选择。对已存在合并症的长期影响需要进一步研究。
