Disorders of Sexual Differentiation

Question 1

SRY

Answer 1

on y chromosome

makes gonad testes

Question 2

MIS/AMH

Answer 2

causes mullerian ducts to regress

Question 3

46 XX DSD

Answer 3

Congenital Adrenal Hyperplasia (CAH)
21-hydroxylase deficiency
3 β hydroxysteroid dehydrogenase deficiency
11 β hydroxylase deficiency (effects estrogens less)
- hyponatremia, hyperkalemia, hypotension, cardio collapse
 Maternal ingestion of androgenic steroids
 Androgen-producing tumors in mother or fetus
 This is the most common cause of ambiguous
genitalia in the newborn

Question 4

Diagnosis of CAH

Answer 4

Serum 17 OHP≥5 ng/ml is diagnostic, < 2 ng/ml rules out

 Prenatal diagnosis is also available (high 17 OHP or DNA test)

Question 5

46 XY DSD

Answer 5

androgen synthesis disorders
3β hydroxysteroid dehydrogenase deficiency (rare)
 11α hydroxylase deficiency (hypertensive, ↑DOC)

Androgen action disorders
 5 α reductase deficiency (autosomal
recessive)
 Androgen insensitivity (x-linked recessive)-need removal of testes

Swyer Syndrome - typical female external genitalia. The uterus and fallopian tubes are normally-formed, but the gonads (ovaries or testes) are not functional
Complete gonadal dysgenesis- need removal of ovaries

Question 6

ovotesticular DSD

Answer 6

More than 50% are 46XX, but they can be
chimeric 46XX/46XY or mosaic
 The amount of functional testicular tissue
determines internal reproductive tissues (often have both)
 Most will have uterus and ambiguous genitalia
 60% menstruate

Question 7

Physical exam findings concerning for DSD

Answer 7

7% of newborn females with an inguinal hernia
and no cervix are either 46 XY DSD (CAH) or
ovotesticular DSD (mixed gonadal dysgenesis)
 A male with a hypospadias and unilateral or
bilateral cryptorchidism has up to a 50% chance
of DSD (hypospadias is common but less than
1% will have associated cryptorchidism)

Question 8

Evaluation for ambiguous

Answer 8

Electrolytes to rule out salt wasting
 Thorough physical exam—consider malformation
syndrome vs just ambiguous genitalia. Gonads inferior
or at the inguinal canal are probably testes
 Maternal history, especially androgen ingestion,consanguinity, history of unexplained neonatal deaths
 Karyotype, 17 OHP, DHEAS, testosterone, LH, FSH,
dihydrotestosterone
 Imaging: Ultrasound, retrograde genitogram, MRI

Question 9

Uterine didelphys

Answer 9

leaking with tampon
80% renal agenesis
transverse vaginal septum