AssessmentsAndrogen insensitivity syndrome
Androgen insensitivity syndrome
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 20-year-old woman comes to the office because she has not had her first menstrual period. Physical examination shows normal breast development, but minimal axillary and pubic hair. Pelvic examination shows that the vagina ends in a blind pouch, and masses are palpable in the inguinal region. Which of the following karyotype findings is most likely?
Androgens are responsible for primary sex characteristics like development of the penis and testes as well as secondary sex characteristics like height and body shape, so in androgen insensitivity syndrome all of these can be affected.
Okay, normally, very early on in fetal life, male and female genital tissues are undifferentiated and look identical.
In males, a gene on the Y chromosome, called the sex-determining region Y gene, or SRY gene for short, helps the fetal gonads turn into the testes.
A small fraction of testosterone, gets converted by the enzyme 5α- reductase into its more potent form, called dihydrotestosterone, which is mostly responsible for development of male external genitalia.
Looking closely at these structures, at the top there’s the genital tubercle, which is a small projection.
Just below that, there's the urethral groove, which is the external opening of the urogenital sinus or the future urethra and bladder and is surrounded by the urethral folds and the labioscrotal swellings.
At the same time, the testes also produce a hormone called anti-Müllerian hormone which prevents the Müllerian ducts from developing into the female reproductive tract and instead makes them degenerate.
About two months before birth, testosterone helps the testes descend from the abdomen into the future scrotum and later on, in puberty, testosterone helps sperm cells mature - a process called spermatogenesis.
In females, there’s no Y chromosome so the SRY gene is absent.
As a result, ovaries develop from the internal gonads, and androgen levels remain relatively low, so the genital tubercle remains small, forming the clitoris and the urethral folds and labioscrotal swellings remain unfused or separate, forming inner and outer skin folds that surround the opening of the vagina and are called labia minora and labia majora.
In androgen insensitivity syndrome, XY-individuals have testes that produce androgens, but these hormones can’t exert their action, because there’s a defect in the androgen receptor on various target tissues like the external genitalia, genital ducts, and the testes itself.