由于21-羟化酶缺乏症导致的典型先天性肾上腺增生(CAH)是一种罕见的常染色体隐性遗传疾病,其特征是皮质醇缺乏和雄激素产生过多。目前的护理标准是糖皮质激素(GC)治疗,有时还有盐皮质激素,替代内源性皮质醇缺乏症;然而,通常需要超生理GC剂量来减少过量的雄激素产生。监测/滴定GC处理仍然是一个主要挑战,在评估治疗充分性方面没有达成一致。这项研究调查了有关经典CAH成年人当前治疗方法和未满足需求的专家意见。
通过在线问卷调查,对成人内分泌学家进行了两轮Delphi程序的改良。调查问题分为三类:实践特征/CAH经验,GC管理,和未满足的需求/并发症。第1轮的匿名汇总数据作为第2轮的反馈提供。使用描述性统计分析两轮的反应。共识被先验地定义为:完全共识(100%,n=9/9);接近共识(78%至<100%,n=7/9或8/9);无共识(<78%,n<7/9)。
同样的九名小组成员参加了两轮调查;五名(56%)位于北美,四名(44%)位于欧洲。大多数小组成员(78%)在大多数患者中使用氢化可的松,但有2人(22%)首选泼尼松/泼尼松龙。小组成员同意(89%)使用临床表现和雄激素/前体实验室值的平衡来最好地评估适当的控制;对于收集雄激素测试样品的最佳时机或表明良好控制的实验室值没有达成共识。尽管在CAH管理的许多方面缺乏共识,小组成员同意许多疾病和GC相关并发症的重要性,并且对新的治疗方法有大量未满足的需求。根据目前可用的治疗方法,小组成员报告说,46%的经典CAH患者没有优化的雄激素水平,无论GC剂量。
在这项研究中获得的有限领域的共识反映了经典CAH成人治疗实践的差异性,即使是在治疗这一人群方面有专长的临床医生。然而,所有小组成员都同意需要经典CAH的新疗法以及许多疾病和GC相关并发症的重要性,用目前可用的治疗方法很难管理。
Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive condition characterized by cortisol deficiency and excess androgen production. The current standard of care is glucocorticoid (GC) therapy, and sometimes mineralocorticoids, to replace endogenous cortisol deficiency; however, supraphysiologic GC doses are usually needed to reduce excess androgen production. Monitoring/titrating GC treatment remains a major challenge, and there is no agreement on assessment of treatment adequacy. This study surveyed expert opinions on current treatment practices and unmet needs in adults with classic CAH.
A modified two-round Delphi process with adult endocrinologists was conducted via online questionnaire. Survey questions were organized into three categories: practice characteristics/CAH experience, GC management, and unmet needs/complications. Anonymized aggregate data from Round 1 were provided as feedback for Round 2. Responses from both rounds were analyzed using descriptive statistics.
Consensus was defined a priori as: full
consensus (100%, n=9/9); near
consensus (78% to <100%, n=7/9 or 8/9); no
consensus (<78%, n<7/9).
The same nine panelists participated in both survey rounds; five (56%) were based in North America and four (44%) in Europe. Most panelists (78%) used
hydrocortisone in the majority of patients, but two (22%) preferred prednisone/prednisolone. Panelists agreed (89%) that adequate control is best evaluated using a balance of clinical presentation and androgen/precursor laboratory values; no consensus was reached on optimal timing of collecting samples for androgen testing or laboratory values indicating good control. Despite lack of
consensus on many aspects of CAH management, panelists agreed on the importance of many disease- and GC-related complications, and that there is a large unmet need for new treatments. With currently available treatments, panelists reported that 46% of classic CAH patients did not have optimized androgen levels, regardless of GC dose.
The limited areas of
consensus obtained in this study reflect the variability in treatment practices for adults with classic CAH, even among clinicians with expertise in treating this population. However, all panelists agreed on the need for new treatments for classic CAH and the importance of many disease- and GC-related complications, which are difficult to manage with currently available treatments.