21羟化酶缺陷症患者睾丸肾上腺残余瘤的临床特征及相关因素  

Clinical characteristics of testicular adrenal rest tumor and factors associated with its occurrence in 21-hydroxylase deficiency patients

作　　者：高寅洁 于冰青 卢琳[1] 伍学焱[1] 茅江峰[1] 王曦[1] 童安莉[1] 陈适[1] 聂敏[1] Gao Yinjie;Yu Bingqing;Lu Lin;Wu Xueyan;Mao Jiangfeng;Wang Xi;Tong Anli;Chen Shi;Nie Min(Department of Endocrinology,Peking Union Medical College Hospital,Key Laboratory of Endocrinology,National Health Commission,Beijing 100730,China)

机构地区：[1]北京协和医院内分泌科,国家卫生健康委员会内分泌重点实验室,北京100730

出　　处：《中华医学杂志》2020年第24期1850-1855,共6页National Medical Journal of China

基　　金：国家重点研发课题(2016YFC0905102);国家自然科学基金(81971375)。

摘　　要：目的分析21羟化酶缺陷症(21-OHD)患者睾丸肾上腺残余瘤(TART)的发生情况及临床特点,探讨可能与TART发生相关的因素。方法纳入2018年1至12月于北京协和医院内分泌科就诊的27例男性21-OHD患者,并收集其临床和血生化资料。利用Sanger测序方法和多重连接探针扩增技术(MLPA)明确CYP21A2基因突变,并根据21羟化酶残余活性将患者分为Null组(酶活性完全丧失,3例)、A组(酶活性存留0~<1%,9例)、B组(酶活性存留1%~5%,7例)、C组(酶活性存留20%~50%,2例)和D组(携带尚未报道对应酶活性的罕见突变,6例)。双侧阴囊超声检查患者是否出现TART及其形态特征。结果21-OHD男性患者27例,年龄(17.4±9.3)岁。其中15例(15/27,55.6%)出现TART病变,以青少年患者最为多见,最小的仅4岁。超声下多为双侧低回声病变。合并TART的患者17α-羟孕酮(17-OHP)及孕酮水平均高于未合并TART的患者[17-OHP:199.6(62.1,232.7)nmol/L比7.4(3.2,105.0)nmol/L,P=0.003;孕酮:97.1(42.0,126.8)nmol/L比5.4(0.7,20.0)nmol/L,P=0.004]。TART的发生与基因型分组存在相关性,严重影响酶活性的Null组和A组患者,其出现TART的可能性高于轻微影响酶活性的B和C组(8/12比4/9,P=0.021)。结论TART在21-OHD患者中较为常见,其与17-OHP等激素水平及CYP21A2基因型存在一定相关性,多发生于病情控制不佳的21-OHD患者。21-OHD患者TART病变的早期筛查可能对预后有重要意义。Objective To analyze the occurrence and clinical characteristics of testicular adrenal rest tumor(TART)in 21-hydroxylase deficiency(21-OHD)patients,and further explore the possible factors related to the occurrence of TART.Methods Twenty-seven male 21-OHD patients who visited Peking Union Medical College Hospital from January to December 2018 were enrolled and their clinical and biochemical data were collected.The CYP21A2 mutations were identified by Sanger sequencing and multiple ligation probe amplification(MLPA).Patients were divided into different subgroups according to the residual activity of 21-hydroxylase:Null(residual enzymatic activity 0,3 cases),group A(0-<1%,9 cases),group B(1%-5%,7 cases),group C(20%-50%,2 cases)and group D(6 cases).The ultrasound of testis was used to detect whether there was TART and its morphological characteristics.Results Among 27 patients with 21-OHD[average age(17.4±9.3)years],55.6%(15/27)had TART lesions,most of them were adolescents,and the youngest was only 4 years old.The lesions were mostly bilateral and hypoechoic.The levels of 17α-hydroxyprogesterone(17-OHP)and progesterone in patients with TART were higher than those in patients without TART[17-OHP:199.6(62.1,232.7)nmol/L vs 7.4(3.2,105.0)nmol/L,P=0.003;progesterone:97.1(42.0,126.8)nmol/L vs 5.4(0.7,20.0)nmol/L,P=0.004].There was a correlation between the occurrence of TART and genotype of CYP21A2.Patients with Null and A genotypes were more likely to have TART than those with B and C genotypes(8/12 vs 4/9,P=0.021).Conclusions TART is common in 21-OHD male patients,which is related to 17-OHP and CYP21A2 genotype.It is of great significance for the early screening of TART in 21-OHD patients.

关 键 词：肾上腺增生 先天性 21羟化酶缺陷症 睾丸肾上腺残余瘤 基因型 17α-羟孕酮 

分 类 号：R737.21[医药卫生—肿瘤] R586[医药卫生—临床医学]