5-Alpha Reductase Deficiency

Snapshot

• A 16-year-old girl presents with absence of breast development and menarche. This is stressful to her because her friends have experienced this and she has not. On physical exam, the patient has relatively broad shoulders and narrow hips with mild facial hair. On genital inspection, there is an enlarged phallus and absence of a uterus. Testosterone-to-DHT ratio is elevated with normal LH level.

Introduction

• Autosomal recessive defect in 5α-reductase in XY males 
  • impaired conversion of testosterone to dihydrotestosterone (DHT) 
    • leads to impaired virilization during embryogenesis
    • normal testosterone production and normal estrogen levels
    • normal or elevated LH
    • normal internal genitalia
  • ambiguous genitalia until puberty, where elevated testosterone levels leads to masculinization
  • DHT plays an important role in the development of the external genitalia
    • also primary androgen for the prostate gland
• Epidemiology
  • not life threatening
• usually identified in the neonatal period due to ambiguous genitalia

Presentation

• Physical symptoms
  • normal internal gonads
  • ambiguous genitalia 
    • prepubescence
  • gynecomastia is very rare
• a hallmark for androgen insensitivity syndrome

Evaluation

• Usually diagnosed in infancy
• Laboratory testing
  • karyotyping
    • XY male
  • testosterone-to-DHT ratio
• > 20  

Differential Diagnosis

• Androgen insensitivity syndrome
• 17β-hydroxysteroid dehydrogenase 3 deficiency

Treatment

• Patient education
• Gender assignment
• In those with maintained female gender role
  • gonadectomy
  • estrogen therapy
• In those with maintained male gender role
  • surgical intervention
• surgical correction of hypospadias, and in those with cryptorchidism

Prognosis, Prevention, and Complications

• Complications
  • if cryptorchidism, increased risk of testicular cancer