199 Sex Differentiation

Question 1

What are the expected findings (internal and external genitalia) in a 46, XX individual with translocation of SRY?

Answer 1

internal: gonads are testicles, Wolffian structures are stabilized whereas Mullerian structures disappear
external: male appearing external genitalia

Question 2

What is the role of sertoli cells in sexual differentiation?

Answer 2

sertoli cells produce anti-mullerian hormone which causes regression of mullerian ducts

Question 3

Why is 17-OH progesterone elevated in 21-hydroxylase deficiency? Why does this condition have elevated testosterone levels?

Answer 3

abnormal production or absence of 21-hydroxylase creates a block in the usual cortisol levels

the body senses lack of cortisol and the pituitary gland produces extra ACTH to stimulate production of cortisol

deficient 21-hydroxylase leads to buildup of the product prior to the enzyme, 17-OH progesterone, which is shunted towards the unblocked testosterone pathway

Question 4

List diagnoses which would produce a 46, XY individual with palpable testes and ambiguous external genitalia?

Answer 4

5-alpha reducates deficiency

PAIS

CAH (3-beta-hydroxysteroid dehydrogenase deficiency, 17,20-lyase deficiency, and 17-alpha-hydroxylase deficiency

Question 5

What is the internal and external anatomy associated with mixed gonadal dysgenesis?

Answer 5

internal: streak gonad, dysgenetic testicle, unilateral mullerian structures
external: variable

Question 6

What is the internal and external anatomy of ovotesticular DSD?

Answer 6

internal: ovrian and testicular gonads, maybe mullerian structures
external: variable

Question 7

What is the major cause of ovotesticular DSD?

Answer 7

SOX9 duplication

Question 8

What is the internal and external anatomy associated with complete gonadal dysgenesis?

Answer 8

internal: streak gonads, mullerian structures
external: female typical

Question 9

What is the most common cause of complete gonadal dysgenesis?

Answer 9

SF1 and SOX9 mutations

Question 10

Which of the following is least likely to have puberty?

Answer 10

complete gonadal dysgenesis

Question 11

What are the internal and external genitalia associated with complete androgen insensitivity?

Answer 11

internal: testicles, no mullerian
external: female typical

Question 12

What is the most likely cause of complete and partial androgen insensitivity?

Answer 12

AR mutation

Question 13

What are the internal and external genitalia associated with 5-alpha reductase deficiency?

Answer 13

internal: testicles
external: variable

Question 14

Is there puberty in complete androgen insensitivity?

Answer 14

partially - only breast development

Question 15

What internal and external genitalia are associated with testicular DSD (XX + SRY)?

Answer 15

internal: testicles
external: male typical

Question 16

What internal and external genitalia are associated with ovotesticular DSD?

Answer 16

internal: ovary and testicle, variable mullerian
external: variable

Question 17

What are the causes of ovotesticular DSD?

Answer 17

SOX9 duplication

Question 18

What are the internal and external genitalia associated with CAH-21 hydroxylase deficiency?

Answer 18

internal: ovaries, mullerian structures
external: variable

Question 19

Infant presents with penoscrotal hypospadias; scrotal tissue rugated on the right, but flat on the left; right testis palpable in the scrotum, but left testis nonpalpable; mullerian structures on ultrasound.

What is the most likely diagnosis?

a) mixed gonadal dysgenesis
b) testicular DSD
c) complete gonadal dysgenesis

Answer 19

a) mixed gonadal dysgenesis

Question 20

Infant presents with prominent clitorophallic structure, single urogenital sinus, fused labioscrotal tissue (no hyperpigmentation or rugation); no palpable gonads; mullerian structures on ultrasound; 46,XX karyotype.

What is the most likely diagnosis?

a) testicular DSD
b) partial androgen insensitivity syndrome
c) congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Answer 20

c) congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Question 21

A 16 yo girl presents for primary amenorrhea. She began breast development at age 11. Pubic hair is Tanner 2. She has a few wispy axillary hairs. On exam her external genitalia appears phenotypically female, but you palpate 2 inguinal masses.

Which of the following is her likely diagnosis?

a) 5-alpha reducates deficiency
b) mixed gonadal dysgenesis
c) complete androgen insensitivity syndrome
d) 21-hydroxylase deficiency

Answer 21

c) complete androgen insensitivity syndrome

Question 22

Which cells of male genitalia are responsible for mullerian regression?

Answer 22

sertoli cells (via AMH production)

Question 23

What are the following genes important for in sexual development:

SF1

SOX9

SRY

WNT4

Answer 23

SF1 - gonads and adrenal glands

SOX9 - testis (must be suppressed for ovarian development)

SRY - testis

WNT4 - ovaries

Question 24

What is the role of 5-alpha reductase in genital development?

Answer 24

converts testosterone to DHT

masculinization of external genitalia

Question 25

What is the genotype and phenotype of ovotesticular DSD?

Answer 25

genotype: anything but usually has SOX9 duplication
phenotype: variable internal genitalia, variable external genitalia

Question 26

What is the cause of complete/partial gonadal dysgenesis?

Answer 26

SF1 or SOX9 mutations in an XY individual

Question 27

What is the cause of androgen insensitivity syndromes?

Answer 27

XY genotype with a mutation in the androgen receptor