Abnormal sexual development, precocious puberty Flashcards
When does sexual differentiation begin to take place in utero?
6th week of gestation (ovaries vs testes)
How do gonads become testes?
Testes determining factor = SRY on the distal short arm of the Y chromosome (otherwise default is female)
When and how do duct systems differentiate in utero?
8th week of gestation; AMH produced by males’ Sertoli calls cause regression of the Mullerian system and stimulate abdominal descent of testes
What causes development of Wolffian ducts into epididymis, vas deferens, and seminal vesicles?
Testosterone produced by Leydig cells after 8 weeks of gestation (must be very high direct exposure)
What causes descent of testes through inguinal canal?
Testosterone
Genital tubercle becomes…
Penis vs clitoris
Urogenital sinus becomes…
Urethra vs urethra / vagina/ labia minora
Labioscrotal swellings become…
Scrotum vs labia majora
Differential diagnosis for 46 XX disorders where females are masculinized
CAH, elevated maternal androgens, aromatase deficiency
Timing for completion of female sexual differentiation
20 weeks gestation
CAH internal anatomy
Normal female anatomy because no AMH
Differential diagnosis for 46 XY disorder where males are incompletely masculinized
Androgen insensitvity, 5 alpha reductase deficiency, (less commonly) testosterone biosynthesis defects, gonadotropic resistant testes, AMH deficiency
Normal breast development, no pubic hair, female external genitalia, undescended testes
Androgen insensitivity
Treatment for AIS
Gonadectomy at 16-18 y/o after endogeneous hormonal changes of puberty
Masculinization at puberty, ambiguous genitalia
5 alpha reductase deficiency
46 XY with bilateral dsygenesis of testes and thus internal and external female anatomy without working ovaries
Swyer syndrome
Most common gonadal tumor for individuals who are 46 XY with female phenotype
Gonadoblastoma (also dysgerminoma and embryonal carcinoma)
Anorchia
“Disappearing testes syndrome” where testes regressed before full genitalia could develop
Molecular trigger of adrenarche
Rise of adrenal androgens: DHEA, DHEAS, androstenodione (independent of GnRH axis)
Molecular triggers of growth in a female
Estrogen and growth hormone (mediator IGF-1)
Definition of precocious puberty
Pubertal changes before age 8 y/o
Most common causes of precocious puberty
Idiopathic (74%)
CNS (7%)
Ovarian cyst or tumor (11%)
McCune-Albright syndrome (5%)
McCune-Albright syndrome presentation
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
Why does bone age matter?
Estrogen can cause early fusion of growth plates which leads to early growth then stunted adult height
Treatment of precocious puberty
For idiopathic, GnRH agonist
Additional work-up after diagnosis of Mullerian agenesis
Imaging of renal tract (CT urogram, IVP, or renal US)
Treatment of delayed puberty
Low dose estrogen followed by progesterone with menstruation or 12-24 months later
