Background: The approach to investigating a newborn with a suspected DSD is likely to vary between centres and may be influenced by local availability.
Method: To explore the current diagnostic practice and needs, an international survey of 124 paediatric endocrinologists, identified through DSDnet and the I-DSD Registry, was performed in 2014.
Results: A total of 77/124 (62%) clinicians, in 74 centres, from 38/42 (91%) countries responded to the survey. In a suspected case of 46,XY DSD, the investigations that would be performed routinely within the first week of presentation included testosterone (97%), karyotype (96%), ultrasound (94%), 17-hydroxy-progesterone (83%), androstenedione (75%), dihydrotestosterone (DHT, 73%), X/Y probes by FISH/PCR (69%), cortisol (68%), and anti-Müllerian hormone (AMH, 58%). Second-line investigations included further imaging (86%), array CGH (69%), cortisol ACTH stimulation (69%), hCG stimulation test (62%), and urinary steroid profile (USP, 51%). The diagnostic tests reported to be not available locally but desirable included USP (43%), array CGH (31%), DHT (21%), and AMH (21%). Clinicians reported that, locally, they had access to the following genetic tests: SRY (75%), AR (66%), SRD5A2 (53%), NR5A1 (53%), exomic/genomic analysis (51%), WT1 (51%), DAX1 (49%), SOX9 (44%), and a wider panel of genes (44%). The genetic tests the clinicians would perform routinely in a case of 46,XY DSD included: SRY (51%), AR (43%), SRD5A2 (31%), and NR5A1 (26%), while they would perform DAX1 (73%), WT1 (71%), NR5A1 (65%), SRD5A2 (62%), and SOX9 (61%) only if family history or biochemistry were suggestive. For diagnosing 5a reductase deficiency, 49% of them reported genetic testing as the single most preferable test whilst 38 and 13% reported testosterone:DHT ratio and USP respectively. The corresponding figures for 17bHSD3 deficiency were 55, 32, and 13%.
Conclusion: There is considerable variation in the diagnostic evaluation of a newborn with suspected DSD between centres and access to specialist tests may influence this factor. Molecular genetic testing is increasingly common in specialist centres. Clearer guidance in complex cases and collaboration through a network of centres could rationalise the need as well as access to diagnostic investigations.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology