Koren Ilana, Weintrob Naomi, Kebesch Rebekka, Majdoub Hussein, Stein Nili, Naor Shulamit, Segev-Becker Anat
Pediatric Endocrinology Unit, Carmel Medical Center, Clalit Health Services, Haifa 3436212, Israel.
Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
J Clin Endocrinol Metab. 2024 Feb 20;109(3):852-857. doi: 10.1210/clinem/dgad546.
Recent guidelines suggest that patients with nonclassic congenital adrenal hyperplasia (NCCAH) stop glucocorticoid therapy after achieving adult height. However, these guidelines do not differentiate between NCCAH genotype groups.
Compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation vs subjects with biallelic mild (mild/mild) mutations.
Retrospective evaluation of the medical records of 122 patients who presented with postnatal virilization and were diagnosed with NCCAH. Patients underwent standard intravenous 0.25 mg/m2 ACTH stimulation testing. Those with stimulated 17OHP level ≥40 nmol/L were screened for the 9 most frequent CYP21A2 gene mutations followed by multiplex ligation-dependent probe amplification. A stimulated cortisol level below 500 nmol/L was defined as partial cortisol deficiency.
Patients were subdivided into 3 genotype groups: 77 carried the mild/mild genotype, mainly homozygous for p.V281L mutation; 29 were compound heterozygous for mild/severe mutation, mainly p.V281L/p.I2Splice, and 16 were heterozygous for p.V281L, and were excluded from statistical evaluation. Stimulated cortisol levels were significantly lower in the mild/severe than in the mild/mild group (mean ± SD, 480 ± 90 vs 570 ± 125 nmol/L, P < .001). The mild/severe group exhibited a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs 28/71, 39%, P = .004). Peak 17OHP was significantly higher in the mild/severe group (198 ± 92 vs 118 ± 50 nmol/L, P < .001).
The high rate of partial adrenal insufficiency in the mild/severe group underscores the need to carefully consider the value of glucocorticoid therapy cessation and the importance of stress coverage in this group.
近期指南建议非经典型先天性肾上腺皮质增生症（NCCAH）患者在达到成人身高后停止糖皮质激素治疗。然而，这些指南并未区分NCCAH基因型组。
比较携带一个轻度和一个重度（轻度/重度）突变的NCCAH患者与双等位基因轻度（轻度/轻度）突变患者在促肾上腺皮质激素（ACTH）刺激下的皮质醇和17-羟孕酮（17OHP）水平，以及部分皮质醇缺乏的发生率。
对122例出生后出现男性化并被诊断为NCCAH的患者的病历进行回顾性评估。患者接受标准静脉注射0.25mg/m²ACTH刺激试验。对刺激后17OHP水平≥40nmol/L的患者进行9种最常见的CYP21A2基因突变筛查，随后进行多重连接依赖探针扩增。刺激后皮质醇水平低于500nmol/L被定义为部分皮质醇缺乏。
患者被分为3个基因型组：77例携带轻度/轻度基因型，主要为p.V281L突变纯合子；29例为轻度/重度突变复合杂合子，主要为p.V281L/p.I2Splice，16例为p.V281L杂合子，被排除在统计评估之外。轻度/重度组刺激后的皮质醇水平显著低于轻度/轻度组（均值±标准差，480±90 vs 570±125nmol/L，P<.001）。轻度/重度组部分皮质醇缺乏的发生率显著更高（21/28，75% vs 28/71，39%，P=.004）。轻度/重度组的17OHP峰值显著更高（198±92 vs 118±50nmol/L，P<.001）。
轻度/重度组部分肾上腺功能不全的高发生率强调了在该组中仔细考虑停止糖皮质激素治疗的价值以及应激覆盖的重要性。
