endocrinology of pregnancy

Question 1

Hormonal Changes in Pregnancy- Endocrine System

Answer 1

1. Insulin sensitivity early-resistance later (GDM). 2. Earlier conversion to fatty acid metabolism due to  maternal glycogen stores from fetal-placental glucose demands–fasting ketones. 3. Changes in thyroid hormone levels (hCG). 4. increased iodine requirements (goiter, hypothyroid). 5. Changes in autoimmunity (PPT). 6. Estrogen induced pit growth (Sheehan’s)

Question 2

Cardiovascular and Hematologic Changes during pregnancy

Answer 2

1. Increased CO. 2. decreased systemic vascular resistance causes decreased BP. No change in pts with pulm HTN. 3. Increased HR. 4. increased blood volume (anemia of pregnancy)

Question 3

Respiratory/Acid Base Changes from Hormones during pregnancy

Answer 3

1. Increase in Tidal Volume, Minute Ventilation leading to Resp Alkalosis. 2. Compensated Metabolic Acidosis leads to lower buffering capacity (earlier DKA). 3. Increase in O2 consumption. 4. Nasal mucosal edema (stuffy nose, sinusitis)

Question 4

Renal Changes in Pregnancy

Answer 4

1. Increased GFR (clearance of iodine, drugs) -BUN and Cr decrease. 2. Increased renal blood flow. 3. Altered tubular function (glucosuria). 4. decreased ureteral ureteral peristalsis (pyelo). 5. Lowered osmostat for vasopressin release and thirst (hyponatremia)

Question 5

GI Changes in Pregnancy

Answer 5

1. decreased LES (GERD, aspiration pneumonia). 2. decreased stomach emptying, peristalsis (gastroparesis, delayed absorption, constipation). 3. decreased GB emptying (cholestasis)

Question 6

2. List the four major polypeptide releasing hormones produced by the placenta.

Answer 6

CRH (20-fold increase at term), GnRH (stims hCG), GHRH, TRH

Question 7

describe levels of the placental hormones hCG, hPL, hPGH and CRH over the course of the pregnancy

Answer 7

hCG: starts rising at day 8, then drops at 10-12 weeks and plataues. hPL: increases continuously from 5-10 weeks to labor. hPGH: increases continously from 10 wks to labor. CRH: starts increasing at week 25

Question 8

functions of hCG, hPL, hPGH and CRH

Answer 8

hCG maintains the corpus luteum in early pregnancy. hPL participates in the metabolic adjustments that deliver nutrients to the developing fetus. hPGH contributes to insulin resistance of pregnancy. CRH likely plays a role in parturition

Question 9

3. Name the major steroid hormones produced by the placenta.

Answer 9

progesterone, estrogen, Vit D

Question 10

6. Identify the trophoblastic cell type primarily responsible for hormone production.

Answer 10

syncytiotrophoblast- multinuclear layer on surface of villi. Directly bathed by maternal blood within intervillous space. Separated from fetal blood by several layers of tissue. Net transfer of steroids and polypeptide hormones to maternal blood is&raquo_space;> fetus

Question 11

how do levels of estrogen and progesterone change over pregnancy

Answer 11

Both continuously rise- by week 10 placenta takes over with hormone production

Question 12

placental transfer

Answer 12

More permeable to lipid soluble molecules. Hormones > 1200 Daltons have minimal access. Hormones actively metabolized by placenta. T4 metabolized to rT3 by Type III Monodeiodinase. Cortisol metabolize Cortisone by 11-B hydroxysteroid dehydrogenase

Question 13

structure of hCG

Answer 13

Alpha subunit similar to LH, FSH and TSH. Beta subunit is similar to LH but unique C termina

Question 14

hCG functions

Answer 14

1. Maintains corpus luteum steroid (especially progesterone) synthesis until 8-10 wks. 2. Regulates differentiation of cytotrophoblast to syncytiotrophoblast; controls trophoblastic invasion. 3. Induces apoptosis of endometrial T-cells to promote immune survival of embryo . 4. TSH activity at high levels. 5. Stimulates fetal Leydig cells to produce fetal testosterone. 6. May cause hyperemesis. 7. Stimulates Relaxin > increases GFR/Renal blood flow and decreases SVR in rats; studies ongoing in humans

Question 15

hCG clinical correlates

Answer 15

hCG has TSH activity first trimester, hCG-induced hyperthyroidism with HG, Lack of hCG doubling 1st trim—missed Ab, No gestational sac; hCG >1500 U/L-ectopic, No cardiac activity; hCG>9000-missed Abm Altered in placental insuff and trisomies: increased hCG in Down’s–decreased in Trisomy 18
hCG has TSH activity first trimester, hCG-induced hyperthyroidism with HG, Lack of hCG doubling 1st trim—missed Ab, No gestational sac; hCG >1500 U/L-ectopic, No cardiac activity; hCG>9000-missed Abm Altered in placental insuff and trisomies: increased hCG in Down’s–decreased in Trisomy 18

Question 16

hPL clinical correlates

Answer 16

1. Originally thought to be insulin resistance hormone of pregnancy. 2. Facilitates mobilization and utilization of FFAs for energy by increasing lipolysis. 3. Both insulin and anti-insulin effects. 4. Stimulates insulin secretion. 5. Weak GH activity and mainly a lactogen—Promotes growth of mammary tissue and stims prolactin

Question 17

hPGH functions

Answer 17

hPGH appears to be the major insulin resistance hormone of pregnancy. replaces pituitary GH by 20 weeks. Does not cross placenta but regultaes IGF-1. Decreased by glucose, increased by hypoglycemia. Potent somatogen.

Question 18

What stimulates progesterone release from placenta

Answer 18

hCG

Question 19

progesterone functions

Answer 19

1. Promotes decidua formation . 2. Substrate for synthesis of cortisol and aldosterone in the definitive zone of the fetal adrenal cortex. 3. Inhibits uterine contractions. 4. Modulates immune system (promotes Th2 ab and suppresses Th1 cell mediated response). 5. Stimulates minute ventilation. 6. Smooth muscle relaxant (GI, uterus; GU). 7. Promotes lobular development in the breast; inhibits milk secretion. 8. May contribute to ↓ SVR

Question 20

progesterone maternal-placental-fetal axis

Answer 20

maternal cholesterol is used to make placental progesterone. This is then used by mom and baby for hormone production

Question 21

progesterone clinical correlates

Answer 21

Progesterone given for luteal phase defects. Progesterone given to prevent preterm labor. Misoprostone acts as abortifacent. Autoimmune ds may improve; worsen PP (MS, PPT, Grave’s). Gastroparesis worsens; GERD, aspiration pneumonia. Ureteral relaxation results in urinary reflux, high risk of pyelonephritis

Question 22

how do estrogen levels change during pregnancy

Answer 22

levels may increase 100 fold. High levels of placental aromatase. DHEAS from mom and baby is converted to estrogens by placenta. 90% of estradiol is secreted into maternal circulation

Question 23

estrogen functions

Answer 23

1. Stimulates growth of myometrium. 2. Induces hypercoagulable state ( clotting factors, fibrinogen). 3. Induces protein synthesis (SHBG, TBG, CBG). Induces lactotrophs;. 4. Peripheral vasodilation ( SVR, BP). 5. Increases C.O. 6. Inc mucosal edema (sinusitis, epistaxis). 7 Incr uterine blood flow and decreased resistance. 8. Inc blood volume (anemia). 9. Inc renal perfusion and GFR (increased proteinuria). Inc TG synthesis. Increased Pit size and vasculature

Question 24

estrogen clinical correlates

Answer 24

risk of thrombosis, worsening of proliferative retinopathy, pituitary size increases so prolactin macroadenomas may enlarge, pit at risk of ischemia, estrogen induced hypertriglyceridemia can cause pancreatitis

Question 25

hypercoagulable state of pregnancy

Answer 25

Stasis (venous flow decreases by 3rd trim), vascular damage (delivery/ C section), hypercoagulabiity. Risk goes back to baseline by 6 weeks post partum