Androgen insensitivity syndrome Flashcards
A 16-year-old individual presents for evaluation of primary amenorrhea. Physical examination reveals normal female external genitalia, scant pubic hair, and a tall stature. There are no palpable masses in the inguinal region or abdomen. The patient denies significant health concerns and has no history of surgeries. Laboratory studies show elevated testosterone and estrogen levels, with increased luteinizing hormone (LH) and normal follicle-stimulating hormone (FSH). Karyotype analysis reveals 46,XY. Which of the following is the most likely diagnosis?
A) Turner syndrome
B) Klinefelter syndrome
C) Androgen insensitivity syndrome
D) Congenital adrenal hyperplasia
E) Müllerian agenesis
Answer: Androgen insensitivity syndrome
Explanation: Androgen insensitivity syndrome (AIS) is a condition caused by mutations in the androgen receptor gene, resulting in end-organ resistance to androgens despite normal or elevated androgen levels. Patients with complete AIS (CAIS) present as phenotypic females despite having a 46,XY karyotype. Clinical features include normal female external genitalia, absent male internal genitalia, cryptorchid testes, sparse or absent pubic hair, and primary amenorrhea due to the absence of a uterus and ovaries. The elevated testosterone and estrogen levels, along with increased LH, reflect the body’s inability to respond to androgens while estrogens are produced via aromatization. Diagnosis is confirmed with karyotype analysis and hormone levels.
Incorrect Answers:
A) Turner syndrome: Typically associated with 45,X karyotype, short stature, and a webbed neck, not elevated testosterone or 46,XY karyotype.
B) Klinefelter syndrome: Characterized by a 47,XXY karyotype and features of male hypogonadism, not a female phenotype.
D) Congenital adrenal hyperplasia: Associated with virilization, ambiguous genitalia in females, and electrolyte disturbances, not a completely female phenotype with absent pubic hair.
E) Müllerian agenesis: Presents with primary amenorrhea and normal female pubic hair development, normal karyotype (46,XX), and normal hormone levels.
What is the prevalence of androgen insensitivity syndrome (AIS) in the male population in the US?
2–5:100,000 genetically male population in the US
What is the etiology of androgen insensitivity syndrome?
X-linked recessive mutation of the AR gene encoding the androgen receptor
What is the karyotype associated with androgen insensitivity syndrome?
46,XY
What is the pathophysiology of androgen insensitivity syndrome?
Defects in the androgen receptor result in varying degrees of end-organ insensitivity to androgens
What are the clinical features of complete androgen insensitivity syndrome?
- female external genitalia and physique (female breast development).
- lacking of upper vagina, uterus, fallopian tubes.
- absent male internal genitalia (lack of prostate)
- cryptorchid testes (within the labia)
- scant or no pubic hair
- primary amenorrhea
- infertility
Why do you breast develop in androgen insensitivity syndrome?
Testosterone normally binds to androgen receptors, and when activated in breast tissue, these receptors suppress estrogen-mediated growth and development, leading to underdeveloped or absent breast tissue.
In complete AIS, individuals with 46,XY karyotype have high testosterone levels but lack functional androgen receptors. Because of receptor insensitivity, testosterone cannot inhibit breast development, allowing breast growth to proceed under the influence of aromatized estrogen.
What are the key diagnostic findings for AIS before puberty?
High testosterone (before puberty)
High LH and estrogen, normal testosterone levels, no virilization (after puberty)
Confirm diagnosis with karyotype and genetic testing of AR gene
What are the key clinical diagnostic findings for AIS after “puberty”?
“Puberty” is in quotes because puberty is biased and doesn’t occur fully.
- It is an Estrogen-Driven Development, where individuals with AIS have testes that produce testosterone, which is just converted to estrogen (via aromatase). This estrogen drives typical female secondary sexual characteristics.
Breasts will develop, but the patient will be experiencing primary amenorrhea.
- Age for primary amenorrhea is 13 with no sex characteristics.
- Age for primary amenorrhea is 15 with sex characteristics.
Patients will have increased LH, increased estrogen, and normal/increased testosterone levels
Yet there is, no virilization
What are the main treatment options for complete androgen insensitivity syndrome?
Estrogen replacement therapy.
Vaginal dilation.
What is the purpose of gonadectomy in patients with androgen insensitivity syndrome?
Prevents malignant transformation of intraabdominal/intralabial gonads
Usually performed after puberty.
What psychological support might be necessary for patients with androgen insensitivity syndrome?
Addressing gender identity concerns and providing psychosocial support for emotional and behavioral issues
