先天性肾上腺皮质增生症21-羟化酶缺陷儿童青少年期并发睾丸内残余瘤致睾丸功能减退风险因素和糖皮质激素强化治疗疗效分析

An evaluation of the risk factors for orchidism and the efficacy of intensive corticosteroids therapy for the complicating testicular adrenal rest tumors in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency during the childhood and pubescent stages

目的探索先天性肾上腺皮质增生症21-羟化酶缺陷儿童青少年患儿并发睾丸内残余瘤(TART)致睾丸功能减退的风险因素和糖皮质激素强化治疗使瘤体消退的疗效。方法纳入分析19例(27例次)21-羟化酶缺陷合并睾丸残余瘤患儿。强化治疗组12例(17例次)。强化治疗应用相当于氢化可的松19mg·m-2·d^-1~30mg·m-2·d^-1的糖皮质激素制剂。未强化对照组7例(7例次)。纵向回顾分析两组从诊断至随访终点以下参数:(1)B超测量的瘤体和睾丸的大小及声像。(2)血清FSH、LH、睾酮、雄烯二酮、17-羟基孕酮以及抑制素-B。(3)睾丸功能减退界定:各年龄至随访终点期间有抑制素B低下和(或)已进入青春期TannerⅣ者血睾酮睾酮低下。(4)治疗方案与TART消退的关系。结果2~18岁TART发生率28.18%,最小年龄2.48岁。强化治疗后追踪(2.0±1.0)年。强化治疗组瘤的消退率显著高于对照组,分别为20/30和1/11(瘤次,P=0.004)。地塞米松联用氢化可的松,并前者剂量≥30%总量时,瘤消退率显著高于不联用,分别为16/20和4/10(P=0.045)。致睾丸功能减退的风险因素与早期诊断有关:诊断时瘤分期>Ⅲ期(P=0.003),睾丸B超声像异常(P=0.003)以及瘤直径>6.95mm,或瘤/睾丸最大径比值>0.435。抑制素-B是最早提示睾丸功能减退的生化标记。结论21-羟化酶缺陷患儿于儿童-青春期合并睾丸内残余瘤并不少见,早期诊断经糖皮质激素强化治疗可使消退,诊断延迟治疗无效并有致睾丸功能减退风险。建议从2岁起定期B超检查睾丸。

Objective To explore the risk factors for orchidism and the curative efficacy of intensive corticosteroids therapy for the testicular adrenal rest tumors (TART) in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) during childhood and pubescent periods. Methods A total 12 cases (27 case-times) with TART were adopted in intensive corticosteroids therapy, 7 cases (7case-times) as control group without intensive therapy. Retrospective analysis following parameters:(1) The testicular volume and the echogenic characteristics of TART by B-mode ultrasound.(2) Serum levels of FSH, LH, testosterone, 17-hydroxyprogesterone, androstendion, and inhibin-B were measured.(3) Orchidism was defined by one of following events: serum level of inhibin-B≤3rd % for normal, and(or) serum level of testosterone<1.42 ng/ml for the individual which is already in Tanner Ⅳ stage.(4) The relationship between regression of TART and intensive therapy project. Results The prevalence of TART in 21-OHD was 28.18% during 2-18 years old, and the youngest age with TART was 2.48 year of old. The regression rate of TART by intensive therapy was higher than that of the control significantly, 20/30 and 1/11(tumor-times) respectively(P=0.004). When the dose of dexamethasone ≥30% of total doses of corticosteroids, the regression rate of TART was higher than those less than 30% ones, or adopted hydrocortisone alone, were both respectively 16/20 and 4/10(P=0.045). The risk factors for orchidism related to early diagnosis: The TARTs stages in diagnosis (≥stages III;P=0.003), the tumor in size, hyperechogenicity in B ultrasound of the tumors(P=0.003). Inhibin-B is the earliest displayed biochemical warker for orchidism. Conclusions The TART could regress when got early diagnosis and adopted intensive corticosteroids therapy on time. Delayed diagnosis was the main risk factor for orchidism. For early diagnosis of TART, we suggest to conduct the scrotal ultrasound regularly started from 2 years of age.