Diagnosis is usually made between birth and puberty. Pseudovaginal perineoscrotal hypospadias presenting with female appearing genitalia and pubertal virilization is the classical syndrome attributed to<unk> R2D, but modern diagnostic methods can diagnose the deficiency shortly after birth and recognize the broad spectrum of presentation. The initial diagnosis of 46,XY DSD is indicated by overt genital abnormality. The objective clinical evaluation of dysmorphic features to diagnose 46,XY DSD for apparent female genitalia include: enlarged clitoris, posterior labial fusion, and inguinal/labial mass. For apparent male genitalia: nonpalpable testes, micropenis, isolated perineal hypospadias, or mild hypospadias with undescended testis. Family history and prenatal history are also taken into account in evaluation. Karyotyping and SRY gene analysis on samples from peripheral leukocytes will exclude sex chromosome abnormalities. With the determination of an XY karyotype and normal SRY, the differential diagnosis of 46,XY DSD is made with endocrinological measurements of T/DHT ratios (which indicate<unk> R2 activity) and precise anatomical imaging since<unk> R2D can be difficult to distinguish from other causes of 46,XY DSD (e.g., partial androgen insensitivity syndrome and 17β- hydroxysteroid dehydrogenase type 3 enzyme deficiencies). The measurement of the serum DHT concentration is challenging since the concentrations are low and DHT has a high level of cross-reactivity. A high level of assay specificity is required to measure concentrations of DHT since serum T levels are generally 10 fold higher than DHT in young males. Endocrinological tests for T/DHT ratios can be difficult to interpret since the normal ratio level varies according to age and severity of<unk> R2 activity impairment. Affected young males of at least pubertal age with normal serum T levels demonstrate elevated T/DHT levels (normal T, lower than normal DHT). Stimulation with human chorionic gonadotropin (hCG) (alternatively, testosterone enanthate) is required in prepubertal children (with stimulation and samples taken over several days) to increase serum testosterone levels for measurement. Interpreting T/DHT ratios in male newborns is especially challenging due to neonatal testosterone surge and higher than normal 5a-reductase type 1 activity. SRD5A2 gene analysis is recommended for diagnosis in newborns. Broadly,<unk> R2D is diagnosed with T/DHT ratios greater than 18 while ratios greater than 30 have been observed in severely affected individuals.<unk> R2D can also be indicated by low ratios of<unk> - to 5ß- reduced steroids, as measured in urine measured via gas chromatography–mass spectrometry. Ultrasonography is the primary means for assessing internal reproductive organs for diagnosis while genitography and voiding cystourethrography are used to resolve structures such as urethral and vaginal tracts. The use of pelvic MRI for diagnostic imaging for<unk> R2D remains controversial.
5α-Reductase 2 deficiency
Isolated 17,20-lyase deficiency
17β-Hydroxysteroid dehydrogenase III deficiency
Aromatase deficiency
Cortisone reductase deficiency
Androgen-induced hermaphroditism
Multiple sulfatase deficiency
Gonadotropin-releasing hormone insensitivity