Society for Endocrinology UK Guidance on the Initial Evaluation of a Suspected Difference or Disorder of Sex Development (Revised 2021)

S. Faisal Ahmed; John Achermann; Julie Alderson; Naomi S. Crouch; Sue Elford; Ieuan A. Hughes; Nils Krone; Ruth McGowan; Talat Mushtaq; Stuart O'Toole; Leslie Perry; Martina E. Rodie; Mars Skae; Helen E. Turner


Clin Endocrinol. 2021;95(6):818-840. 

In This Article

XY DSD With Normal Testosterone, Normal Precursors and low DHT

The type 2 isoenzyme of 5α-reductase type 2 (SRD5A2) is highly expressed in androgen-sensitive tissues and converts testosterone to the more potent androgen, dihydrotestosterone (DHT) required for the development of external male genitalia. At birth, the external appearance of the genitalia of an infant with SRD5A2 deficiency can range from a completely female phenotype to a range of hypospadias severity or, rarely, isolated micropenis. A positive family history is often present in this autosomal recessive condition. In serum, the testosterone: DHT ratio following hCG stimulation often exceeds 30:1 but there are several reports of cases with a lower ratio.[96] In infants over 3–6 months, the defect should be easily identifiable simply on a urine sample which shows a decreased ratio for 5α:5β-reduced C21 and C19 steroids. This biochemical abnormality will also be present in a child who had early gonadectomy. Early diagnosis of this condition is important for sex assignment, and definitive diagnosis in a highly suspicious case may require access to a diagnostic genetics service with a quick turnaround time. With the wide availability of rapid genetic testing, the diagnosis of SRD5A2 deficiency is an example of a condition where molecular genetics is superseding detailed biochemistry as the preferred diagnostic tool.[6] In the infant raised as a boy, application of topical DHT may be a method of assessing the potential of the genitalia to virilise over the longer term. With the discovery of the alternative 'back door' pathway to DHT synthesis, there is a possibility that defects in the aldoketo reductase pathway may also lead to XY DSD[97] but the clinical significance of this defect in the presence of normal 5α-reductase remains debatable.[98]