The adoption more than a decade ago of an international consensus on the diagnosis and treatment of infants born with ambiguous genitalia and disorders of the reproductive system was a huge leap forward.1 Because disorders or differences of sex development (DSD) are rare and often stigmatized, the evidence base is scant, and therefore most of the recommendations still rely on expert consensus and international data sharing.2

Now global efforts are underway to standardize diagnostic protocols, laboratory tests, and reference values.3 The European Reference Network for Rare Endocrine Disorders is among the largest of the networks aggregating information for DSD and other such rare disorders, explained pediatric endocrinologist Sabine E. Hannema, MD, PhD, from the Leiden University Medical Centre in The Netherlands.3

Even though the network will enable clinicians to share knowledge, they will still need to tailor treatment to their individual patients. “It is important to take into account which assay their laboratory uses, what reference values are appropriate to use, and that cut-off values from guidelines or published articles may not be applicable in their situation,” Dr Hannema said. “In addition, we hope to motivate clinicians involved in care for people with DSD to invest time and effort in initiatives to improve standardization of diagnostics and harmonization of laboratory tests.”

Goal: Early Identification

The European Reference Network for Rare Endocrine Disorders hopes to help clinicians provide a swift and accurate diagnosis of infants born with indeterminate genitalia and suspected DSD.3 While genetic testing may inform the prognosis and individualized treatment, there are few recognized genes associated with DSD available for clinical testing.4 Thus, genetic sequencing is among the last few diagnostics recommended for patients with suspected DSD.4 Prenatal genetic testing specifically for DSD is recommended only for patients with a family history of the disorder.4

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The 2016 international consensus statement provided clinicians with diagnostic guidance for DSD and early treatment.3,4 Experts continue to update the consensus statement and have recommended measuring the following as first-line tests for DSD:

● 17α-hydroxyprogesterone (17-OHP)

● Androgen

● Gonadotropin

● Anti-Müllerian hormone (AMH)

● Serum electrolytes4