Pregnancy Flashcards
Maternal GH in pregnancy
[decreases] placental GH replaces pituitary GH in maternal circulation, not detectable at term
Maternal TSH in pregnancy
Maternal T3/T4 in pregnancy
Maternal CRH in pregnancy
Not suppressed by glucocorticoids (may be increased)
Maternal cortisol in pregnancy
- Cortisol binding protein increases in pregnancy -> total circulating cortisol increases more than free cortisol
Maternal prolactin in pregnancy
- Gradual increase across pregnancy
- At term PRL levels 10X (>200 ng/mL)
Maternal estrogens in pregnancy
[increases]
Early pregnancy: Aromatization of maternal androgens
After 20 weeks: Conversion of fetal androgens
- Maternal contribution of DHEA-S is very low
(maternal estrogen very low if fetus lacks adrenal gland)
- Fetus secretes >200 mg DHEA-S daily; >10x of mother
Maternal ACTH in pregnancy
Maternal pituitary ACTH also increased under effect of CRH produce in the cytotrophoblast
Not suppressed by glucocorticoids (may be increased)
Maternal ACTH and cortisol peak in pregnancy
Delivery (increase throughout pregnancy)
CBG in pregnancy
CRH regulators (6)
Vasopressin, NE, AGII, PGs, neuropeptide Y, oxytocin
Protects fetus from maternal increases in cortisol
Placental 11B HSD (converts cortisol to cortisone)
Tx symptomatic prolactinoma (visual disturbance) in pregnancy
- Bromocriptine -> reduce maternal and fetal circulating levels to baseline levels
- Amniotic fluid PRL is unaffected by bromocriptine
Main estrogen of pregnancy
Estriol (E3)
Estriol (E3) in pregnancy
Increases 1000x
16 precursors derived from fetal liver
High estriol implications in pregnancy
- Acute fetal hypoxia
- Multiple gestation
- Risk for preterm labor
- 21-OH CAH
Low estriol implications in pregnancy
- Impending or present fetal demise
- Adrenal hypofunction
- Placental sulfatase deficiency
- Placental aromatase deficiency
- Drug-related effects
Placental sulfatase deficiency inheritance, genetics
- X- linked (essentially all are male); 1 per 2-3000 newborn males
- Complete deletion on the gene within the X (p-region)
Placental sulfatase deficiency diagnosis
Diagnosis: low estriol in pregnancy (not used anymore), high intra-amniotic DHEA-S, normal DHEA, normal androstenedione (differentiate from CAH)
Placental sulfatase deficiency clinical presentation of fetus
Clinically: hyperkeratosis, increased scaling, corneal opacities, pyloric stenosis, cryptorchidism
Placental aromatase deficiency inheritance, genetics
Autosomal recessive; 2 mutations, aromatase gene on chromosome 15
Placental aromatase deficiency clinical implications for mother and fetus (M vs F)
- Maternal hirsutism occurs (still has some peripheral maternal aromatization if mom is not affected by aromatase mutation) – usually in second half of pregnancy, regresses after delivery
- Female fetus is virilized (ambiguous genitalia)
- Female child: hyperandrogenism, multi-cystic ovaries, hypergonadotrophic hypogonadism, absent breast development
- Male child: normal puberty, infertile (estrogen essential for spermatogenesis), no pubertal growth spurt, osteoporosis develops early
From where are Estrone (E1) and Estradiol (E2) derived in pregnancy?
Equally from maternal and fetal precursors
From where is Estetrol (E4) derived in pregnancy?
- Synthesized in the fetal liver from E2 and E3 by the two enzymes 15α- and 16α-hydroxylase
- Alternatively synthesized with 15α-hydroxylation of 16α-hydroxy-DHEA sulfate as an intermediate step
Which estrogen in pregnancy is only detectable during pregnancy?
Estetrol (E4)
Ddx of maternal hirsutism/virilization in pregnancy
- Drug/progestin exposure
- Pregnancy luteomas
- Theca-lutein cysts
- Sertoli-Leydig tumors
Pregnancy luteoma clinical presentation
- Usually discovered incidentally (in third trimester), produce little androgen
- 1/3 reported cases have maternal hirsutism or virilization
- Fetal virilization related to maternal virilization (80% of virilized mothers will deliver virilized female fetuses
Theca-lutein cysts clinical presentation and risk factors
- Associated with elevated HCG
- risk factors – multiples, isoimmunization, molar pregnancy/GTD, gestational diabetes
- 30% of women with theca-lutein cysts will become virilized, no cases of fetal virilization of female fetus
Sertoli-Leydig tumors clinical presentation and association
- Very rare, associated with anovulatory infertility
* Highest risk of maternal and fetal virilization – but low overall
Why fetus escapes virilization
o Aromatase (P450c19/P450arom)
o Increased in SHBG produced by placenta
o Virilization in the Fetus may occur in luteomas due to DHT production
Enzymatic blocks by compartment
- Fetus lacks 3B HSD (conversion of delta 5 androgens to delta 4 androgens)
- Placenta lacks c17 – 17-hydroxylase and 17,20 desmolase
- [Remember: P450 c17 (17alpha hydroxylase) only in theca and P450arom (aromatase) only in granulosa]
Placental progesterone
- Progesterone synthesis independent of quantity of precursor available from fetus (fetus contributes no precursor)
- Progesterone synthesis is derives from MATERNAL cholesterol [Remember: placenta has c17 block, including 17,20 lyase, so placenta CAN make progestins independent of fetal androgens (DHEA)]
- LDL is taken in via endocytosis (mediated by estrogen)
Fetal TSH
Peaks at 28 wks, remains high; T3 low, rT3 high
Fetal FSH/LH
o GNRH neurons develop and migrate week 6 to week 9 (fetal pituitary LH determines fetal T at 12 weeks)
o HPO vascular system complete by 20 weeks
o LH/FSH increase dramatically, reaching a peak between week 20 and week 24
o Decline after midgestation due to negative feedback from placental steroids
o After birth, acute increase in LH and FSH
o Gonadal steroids peak in 3-6 months of age (boys) and 12-18 months of age (girls)
Fetal PRL
Increases throughout
Fetal CRH
Initially secreted at 16 weeks, increase with gestational age, capacity to regulate pituitary ACTH by 2nd tri
Fetal ACTH
Fetal adrenal levels decrease after midgestation
Peptides that do NOT cross the placenta
TSH, insulin, and heparin
