Hypospadias in a male patient with 21-hydroxylase deficiency

A 17-day-old Japanese boy was transferred to the hospital because of vomiting and impaired consciousness. His external genitalia was pigmented associated with small penis and penoscrotal hypospadias. He was diagnosed as suffering from adrenal deficiency according to severe electrolyte abnormality, moderate hypoglycemia, metabolic acidosis and extremely elevated 17-OHP and testosterone levels. He turned out to be a compound heterozygote of CYP21A2 mutations by genetic analysis. Through endocrinological evaluation, he seemed to have normal hypophyseal function, intact testosterone production and appropriate 5-alpha-reductase-2 activity. Partial androgen insensitivity could not be ruled out by slight decrease of SHBG in hCG loading test, although mutation was not detected on androgen receptor gene. This is a rare case of a male patient with 21-hydroxylase deficiency accompanied by hypospadias. As the cause of hypospadias in this case has yet to be elucidated, further investigation and careful follow-up are required.