DDx of Disorders of Sex Development

Question 1

3-Beta-Hydroxysteroid Dehydrogenase Deficiency

Answer 1

Rare form of congenital adrenal hyperplasia that results in decreased production of all 3 groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. In severely affected individuals, decreased mineralocorticoid secretion results in varying degrees of salt wasting in both males and females, and deficient androgen production results in ambiguous genitalia in 46,XY males.

mild defects of HSD3B2 gene may present with premature pubic hair development, hirsutism, irregular menstrual cycles or primary amenorrhea.

Tx: initial replacement of glucocorticoids and mineralocorticoid, plus the addition of sex steroids at appropriate, pubertal age. Good prognosis

Question 2

5-Alpha-Reductase Deficiency

Answer 2

5-alpha-reductase type 2 deficiency (5-ARD) is an autosomal recessive sex-limited condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT). Because DHT is required for the normal masculinization of the external genitalia in utero, genetic males with 5-alpha-reductase type 2 deficiency are born with ambiguous genitalia (ie. 46,XY disorder of sexual development (DSD)).

Question 3

Androgen Insensitivity Syndrome

Answer 3

Androgen insensitivity syndrome (AIS), formerly known as testicular feminization, is an X-linked recessive condition resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete androgen insensitivity syndrome (CAIS) or partial androgen insensitivity syndrome (PAIS), depending on the amount of residual receptor function.