disorders of sex differentiation

Question 1

Disorders of sex development aka intersex

Answer 1

typical differentiation- series of events whereby the sexually indifferent fetus progressively acquires male or female charactersitics in the gonads, genital tract, and external genitalia

Disorders of sexual differentiation- Congenital conditions characterized by a-typical deveopment (chromosomal, external anatomy, internal anatomy, gonadal development)
Clinical implications- hormonal, sex function, fertility, urinary function, malignancy risk, psychosocial challenges

Question 2

when to consider DSD

Answer 2

infancy- overt atypical genitalia, apperent female genitalia with virtilization, apparent male genitalia with microphallus or bilateral non palpable testicles or severe hypospadias or combo of undescended testicles and mild hypospadias, discordance of genical appearance and prenatal karyotype, lab findings

Beyond infancy- hernia in a female, delayed puberty, virilization in female, primary amenorrhea, breast development in male

Question 3

46 XX DSDs

Answer 3

Androgen excess- congenital adrenal hyperplasia (21 hydroxylase deficiency is the most common cause of 46 XX DSD), excessive maternal androgens (virilizing tumors, maternal medications)

Gonadal/ovarian DSD- Ovotesticular DSD, XX Males SRY +/-

Other- Cloacal extrophy, vaginal Atresia, Meyer rokitansky kleister Hauser (MRKH)

Question 4

46 XY DSD overview

Answer 4

defects in androgen production or function- androgen biosynthesis (Defect in DHT production required for genital development at birth not at puberty), Defect in testicular testosterone synthesis (17 ketosteroid reductase deficiency), Defect in adrenal steroidogenesis (CAH)- 3, 17, Scc deficiency, Androgen receptor action - androgen insensitivity syndrome)

Gonadal dysgenesis- XY (complete or partial), XY (Ovotesticular DSD, vanishing testes)

Mullerian inhibiting Substance hormone or receptor deficiencies (Persistance of mullerian Structures)

Question 5

Sex chromosome DSD

Answer 5

Altered Number of Sex chromosomes-
Turners- 45X0, short stature, heart defects, learning disabiliities, infertility (streak gonads, no malignancy risk)

Klinefelters (46XXY, Tall, under virilized men, small atrophic testes, infertility, malignancy risk- breast prostate, lymphoma)

Mosaicism- 45X0, 46 (XY), 46XX, 46XY, wide variability, individulized, XY mosaicism increases gonadoblastom risk in gonads

Question 6

atypical gonadal development

Answer 6

Complete gonadal dysgenesis- failure of gonads to form, complete absence of gonads at time of evaluation

Gondal Dysgenesis- gonadal tissue present, but abnormally formed, there may or may not be germ cell tissue present

Streak gonad- gonadal tissue is present as a streak, typically no viable germ cell tissue present

Mixed Gonadal dysgenesis- asymmetric development, dysgeneic gonad on one side and the contralateral side has normal or absent testicle

Partial gonadal dysgenesis- bilateral gonadal dysgenesis

Ovotestes- histological definition of a gonad having both ovarian and testicular tissue simultaneously

Question 7

CAH

Answer 7

46 XX DSD, 21 OH def (Cyp 21) or 11 or 3B

Question 8

Complete androgen insensitvity

Answer 8

Pubic hair absent (needs T), Breasts are present, menses are absent - no internal structures