目的:46,XY差异/性发育障碍(DSD)是一组相对罕见的异质性疾病,具有不同程度的男性生殖器雄激素不足。应系统地接触此类患者以进行病因诊断。然而,我们缺乏,目前,来自全球这一地区的46,XYDSD中关于诊断方法的临床实践指南。此外,关于不同荷尔蒙测试的时间和截止时间的争论仍然存在,在这些情况下执行。由34名具有管理DSD的兴趣和经验的经验丰富的内分泌学家组成的共识委员会讨论并起草了关于46,XYDSD的诊断方法的共识声明,重点关注相关病史。临床检查,生化评价,成像和遗传分析。
背景:通过对现有文献的系统回顾,然后进行讨论,指导了共识。编写了初步草案,并在成员之间分发。成员们提供了他们的科学投入,所有相关建议都被纳入。委员会成员批准了最终草案。
结论:46,XYDSD的诊断方法应该是多学科的,尽管由经验丰富的内分泌学家协调。我们建议正式的核型分析,即使Y染色体材料已被其他方法检测到。首先应进行细致的病史记录和彻底的从头到脚检查,重点是外生殖器,包括性腺的位置。关于激素和其他生化研究的决定应根据年龄做出,并根据适合年龄的规范进行解释。尽管LC-MS/MS是类固醇激素测量的首选模式,免疫测定,它们广泛可用且较便宜,是可以接受的替代方案。所有46,XYDSD患者均应由训练有素的放射科医生进行腹盆腔超声检查。腹部的MRI和/或腹腔镜检查可用于显示穆勒结构和/或定位性腺。基因研究,其中包括拷贝数变异(CNV)或候选基因的分子测试或下一代测序,然后应根据临床逐步订购,生物化学,荷尔蒙,和放射学发现。
结论:委员会成员认为,需要系统地接触46,XYDSD患者。提出的诊断算法,在协商一致声明中提供,具有成本效益,并辅以适当的遗传研究,可能有助于在大多数此类病例中达到病因诊断。
OBJECTIVE: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice
guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The
consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a
consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis.
BACKGROUND: The
consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members.
CONCLUSIONS: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings.
CONCLUSIONS: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the
consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.