Abnormal sexual development, precocious puberty

Question 1

When does sexual differentiation begin to take place in utero?

Answer 1

6th week of gestation (ovaries vs testes)

Question 2

How do gonads become testes?

Answer 2

Testes determining factor = SRY on the distal short arm of the Y chromosome (otherwise default is female)

Question 3

When and how do duct systems differentiate in utero?

Answer 3

8th week of gestation; AMH produced by males’ Sertoli calls cause regression of the Mullerian system and stimulate abdominal descent of testes

Question 4

What causes development of Wolffian ducts into epididymis, vas deferens, and seminal vesicles?

Answer 4

Testosterone produced by Leydig cells after 8 weeks of gestation (must be very high direct exposure)

Question 5

What causes descent of testes through inguinal canal?

Answer 5

Testosterone

Question 6

Genital tubercle becomes…

Answer 6

Penis vs clitoris

Question 7

Urogenital sinus becomes…

Answer 7

Urethra vs urethra / vagina/ labia minora

Question 8

Labioscrotal swellings become…

Answer 8

Scrotum vs labia majora

Question 9

Differential diagnosis for 46 XX disorders where females are masculinized

Answer 9

CAH, elevated maternal androgens, aromatase deficiency

Question 10

Timing for completion of female sexual differentiation

Answer 10

20 weeks gestation

Question 11

CAH internal anatomy

Answer 11

Normal female anatomy because no AMH

Question 12

Differential diagnosis for 46 XY disorder where males are incompletely masculinized

Answer 12

Androgen insensitvity, 5 alpha reductase deficiency, (less commonly) testosterone biosynthesis defects, gonadotropic resistant testes, AMH deficiency

Question 13

Normal breast development, no pubic hair, female external genitalia, undescended testes

Answer 13

Androgen insensitivity

Question 14

Treatment for AIS

Answer 14

Gonadectomy at 16-18 y/o after endogeneous hormonal changes of puberty

Question 15

Masculinization at puberty, ambiguous genitalia

Answer 15

5 alpha reductase deficiency

Question 16

46 XY with bilateral dsygenesis of testes and thus internal and external female anatomy without working ovaries

Answer 16

Swyer syndrome

Question 17

Most common gonadal tumor for individuals who are 46 XY with female phenotype

Answer 17

Gonadoblastoma (also dysgerminoma and embryonal carcinoma)

Question 18

Anorchia

Answer 18

“Disappearing testes syndrome” where testes regressed before full genitalia could develop

Question 19

Molecular trigger of adrenarche

Answer 19

Rise of adrenal androgens: DHEA, DHEAS, androstenodione (independent of GnRH axis)

Question 20

Molecular triggers of growth in a female

Answer 20

Estrogen and growth hormone (mediator IGF-1)

Question 21

Definition of precocious puberty

Answer 21

Pubertal changes before age 8 y/o

Question 22

Most common causes of precocious puberty

Answer 22

Idiopathic (74%)
CNS (7%)
Ovarian cyst or tumor (11%)
McCune-Albright syndrome (5%)

Question 23

McCune-Albright syndrome presentation

Answer 23

Disseminated cystic bone lesions that easily fracture, cafe au lait spots, precocious puberty (early production of estrogen by the ovaries)
Caused by mutation in alpha subunit of a G protein

Question 24

Why does bone age matter?

Answer 24

Estrogen can cause early fusion of growth plates which leads to early growth then stunted adult height

Question 25

Treatment of precocious puberty

Answer 25

For idiopathic, GnRH agonist

Question 26

Additional work-up after diagnosis of Mullerian agenesis

Answer 26

Imaging of renal tract (CT urogram, IVP, or renal US)

Question 27

Treatment of delayed puberty

Answer 27

Low dose estrogen followed by progesterone with menstruation or 12-24 months later