DSD Flashcards
Red flags in DSD
- Family hx of DSD
- Hx of prenatal exposure to sex hormones
- discordance b/w genital appearance and prenatal karyotype
- vomiting, hypovolemia, and shock in early infancy
In older kids…
- Genital ambiguity
- delayed puberty
- breast development in male
- cyclic, gross hematuria in male
- inguinal hernia in female
- primary amenorrhea
Red Flags PE in DSD
Females
- large clitoris
- palpable testes in labia majora
- congenital labial fusion, usually posterior
- other virilization
Males
- short penis and non-palpable testes
- displaced urethral opening (usually hypospadias) with other findings
- bifid scrotum
When there are red flags…
- Obtain pregnancy hx (meds) and family hx
- very thorough PE
- karyotype and probe for SRY and other Y chromosome markers using FISH
- measure baseline electrolytes until CAH ruled out
- assess adrenal and gonadal fxn
- pelvic/abd US to eval gonads and presence/absence of uterus
CAH
- AR inheritance
- 46 XX > virilized female
- 21-OH deficiency, 11-beta-OH deficiency
- insufficient cortisol production > less negative feedback > increased androgens
- Salt-wasting vs. non
Non-salt wasting 21-OH def
- Simple virilizing CAH
- Labs: low cortisol, elevated ACTH, 17-hydroxyprogesterone, DHEA, and androstenedione, NML electrolytes
Virilization varies
- XX: mild clitoromegaly to phenotypic external male genitalia
- Female internal reproductive organs intact
- XY: phenotypically NML (or hyperpigmented/enlarged) genitalia - delayed dx
Salt wasting 21-OH def
- Lab findings: met acid, hyperkalemia, hyponatremia, hypoglycemia, increased renin (d/t hypovolemia/low salt), low cortisol, elevated ACTH, 17-OHP, DHEA, and androstenedione
- Hypotension
- require steroid replacement daily for life and increased use during stress
Virilization same variation as non-salt wasting except XY often detected within first few weeks of life d/t adrenal crisis and FTT
11beta-OH def CAH
- Labs: hypokalemia, decreased renin, low cortisol and aldosterone, elevated DOC, ACTH, DHEA, DHEAS, and androstenedione, salt wasting rare
- HTN
- degree of virilization varies
Types of CAH that lead to under-virilization
Lipoid CAH and 17 alpha -OH def
Lipoid CAH
- Defect in STAR > negligible prod of all steroids
- cholesterol accumulates in adrenocortical tissues (fatty adrenal glands)
- damaged cells eventually non-functional
- lack of steroid hormones > increased ACTH, LH, FSH, since there’s no neg feedback
- pt present with adrenal crisis, no virilization, hyperpigmentation, and susceptibility to infxn
17-alpha OH def CAH
-Labs: low cortisol, increased DOC and corticosterone, decreased renin, elevated mineralocorticoid activity > hypokalemia, decreased sex steroids and glucocorticoids
-HTN
-XX: phenotypically NML @ birth but no puberty/primary amenorrhea later
XY: under virilization varies
46 XY DSD occur d/t insufficient DHT caused be…
- XY Gonadal dysgenesis (complete = Swyer syndrome, absent testicular tissue; partial = wide range of testicular fxn
- Defect in DHT production > 5alpha-reductase def
- inability to respond to androgens
5 alpha-reductase def
- Absent ability to convert T to DHT
- AR inheritance
- range of enzyme activity > varied phenotypic presentation
XY infants may appear female @ birth and be raised female but at puberty significant virilization can occur
- clitoris may have phallus like growth
- muscle bulk increases and shoulders broaden
- Adam’s apple
- facial hair
- breast development doesn’t occur
complete androgen insensitivity syndrome (CAIS)
- NML appearing labia, clitoris, and vaginal introitus
- undescended testes, no internal female organs
- increase in LH @ puberty drives T/E2 production»_space; female 2nd sex characteristics
Partial androgen insensitivity syndrome (PAIS)
- wide spectrum of masculinization
- @ puberty, virilization poor, gynecomastia
- impaired sexual fxn and fertility in individuals raised as males
