Nguyen Matthew H, Zhang Wei, Pankratz Nathan, Lane John, Chitiboina Prashant, Faucz Fabio R, Mills James L, Stratakis Constantine A, Tatsi Christina
Unit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA.
Academy of Mathematics and System Sciences, Chinese Academy of Sciences, Beijing 100045, China.
J Endocr Soc. 2023 Apr 25;7(6):bvad046. doi: 10.1210/jendso/bvad046. eCollection 2023 May 5.
Successful treatment of endogenous Cushing disease (CD) is often followed by a period of adrenal insufficiency (AI). We performed an exploratory study on genetic factors potentially involved in the hypothalamic-pituitary-adrenal (HPA) axis recovery in patients with CD after remission. We identified 90 patients who achieved remission after surgery and had a minimum of 3 months follow-up. Variants in a selected panel of genes that were rare in the general population and predicted as damaging were retrieved from whole exome sequencing analysis. We did not identify any variant with significant correlation with recovery time after adjusting for multiple comparisons. On gene-specific analysis the gene showed a correlation with shorter duration of postsurgical AI, but both patients with variants later experienced a recurrence. After excluding patients with recurrence, no statistical association was recorded. To conclude, we did not identify a strong genetic modifier of HPA recovery in this exploratory study.
内源性库欣病（CD）成功治疗后常伴有一段肾上腺功能不全（AI）时期。我们对CD缓解后患者下丘脑-垂体-肾上腺（HPA）轴恢复可能涉及的遗传因素进行了一项探索性研究。我们确定了90例术后缓解且至少随访3个月的患者。从全外显子测序分析中检索了一组在普通人群中罕见且预测具有损害性的选定基因中的变异。在进行多重比较校正后，我们未发现任何与恢复时间有显著相关性的变异。在基因特异性分析中，该基因与术后AI持续时间较短相关，但两名携带该变异的患者后来均复发。排除复发患者后，未记录到统计学关联。总之，在这项探索性研究中，我们未发现HPA恢复的强遗传修饰因子。
