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Thyroid Disease in Pregnancy
I. NORMAL THYROID PHYSIOLOGY DURING PREGNANCY
A. Mother
1. Increased thyroxine-binding globulin (TBG) levels after 3 weeks (peak 12-14 weeks, plateau to term)
a. Increased thyroxine (T4), triiodothyronine (T3) (change in T4 greater than change in T3)
b. Decreased resin T3 uptake (RT3U)
c. Normal free thyroxine index (FTI) (T7)
d. Normal free T4, (FT4), free T3. (FT3), and reverse T3, (rT3)
2. Normal thyroid-stimulating hormone (TSH) (but declines slightly as chorionic gonadotropin [hCG] rises), increased responsiveness to thyrotropin-releasing hormone (TRH)
3. Normal T4 production and turnover rates
4. Thyroglobulin (Tg) rises throughout, especially in the last trimester
5. Increased radioactive iodine uptake U) (contraindicated in pregnancy)
a. Increased renal clearance of iodide leads to decreased iodide space
b. Increased thyroidal clearance of iodide leads to normal total iodide uptake
6. Mild thyroid enlargement (goiter) in 15-85 % (different series)
a. Mainly in areas of iodine deficiency; responds to iodine prophylaxis
b. Goiter is seldom seen in North America. If occurs, evaluation warranted
7. Increased basal metabolic rate (BMR): fetus plus increased cardiac output plus respiratory and muscular work
8. Increased cholesterol
B. Fetus
1. Thyroid
a. Follicles recognizable by 8 weeks
b. Iodide trapping by 10-12 weeks
c. Hormonogenesis by 10-15 weeks
(1) T,
(a) Major hormone
(b) Reaches adult levels by 36 weeks
(2) T3
(a) Minimal production until 30+ weeks
(b) Low in amniotic fluid
(a) Major production from T4
(b) High levels in amniotic fluid (300 ng/dL in first half hyperthyroidism, pregnancy, hypothyroidism, thyrotoxicosis, thyroiditis of
pregnancy; decreases to 100 ng/dL at term)
(4) TBG reaches adult levels in third trimester
2. Hypothalamus-pituitary
a. Synthesis of TRH in brain by 6-10 weeks
b. Thyrotrophs recognizable by 12-14 weeks
c. Synthesis of TSH by 12-14 weeks
d. TSH detectable in amniotic fluid after first trimester
e. Umbilical vein sampling: fetal TSH greater than maternal and high
relative to fetal T4
1. Impermeable to TSH
2. Relatively impermeable to T4, T3, rT3
a. Maternal-fetal transfer less than 1-2 %, but in fetal thyroid agenesis,
sufficient maternal transfer (high gradient) to protect CNS until birth
b. No correlation at any time between fetal and maternal levels of T4, FT4,
T3, FT3, rT3, TSH
3. Permeable to
a. TRH
b. IgG and thyrotropin receptor antibodies (TRAb)
(1) Thyroid-stimulating immunoglobulin (TSI)
(2) TSH-binding inhibitory immunoglobulin (TBII)
(3) Long-acting thyroid stimulator (LATS), etc
c. Thionamides
(1) Propylthiouracil TU)
(2) Methimazole (Tapazole)
d. Iodides
e. Propranolol and other B-blockers
4. Cannot organify I- or de-iodinate T4
5. Synthesizes chorionic thyrotxopin (hCT): small amounts, little biologic activity
6. Synthesizes hCG
a. Shares a-chain with TSH
b. Thyrotropic activity: 1 U hCG -- 0.02 uU TSH
c. Peak secretion at 9-12 weeks, approximating 3-10 uU TSH, associated
with decline in TSH. As hCG falls, TSH returns
II. NORMAL THYROID PHYSIOLOGY AT TERM AND POSTPARTUM
A. Representative values at term
Table 1
Test Nonoreenant Maternal B}ood Cord Blood
T4 5-12 ug/dL 16 (9-20) 12 (8-16)
T3 80-190 ng/dL 160 (105-240) 50 (15-85)
rT3 30-80 ng/dL 55 (30-80) 135 (70-200)
TBG 2.5-4.0 mg/dL 8 (4-13) 5 (1-10)
FTI 1.2-4.3 2.5 2.5
TSH I 0.3-5.0/zU/mL 3.0 (0.:5-5) 8.0 (0-18)
B. Changes in neonate ("neonatal T3-toxicosis")
1. TSH surge due to cooling and other factors
a. 10 uU/mL at birth
b. 100-200/zU/ml. at 30 minutes
c. 13/uU/mI. at 48 hours
2. T3 and FT3 increase 800-900% by 24 hours; normal in 14 days
3. T4 increases by 50%, FT4 by 300% by 24 hours; normal in 14 days
4. rT3 stable for 24 hours; normal by 5 days
5. Thyroglobulin (Tg) increases at 6 hours; remains elevated for several months
6. Transient hypothyroxinemia with normal TSH is common in premature infants
( < 2,000 g)--may be associated with later neurologic or mental developmental
problems
C. Changes in mother
1. Gradual decline in TBG
2. T4 and T3 normal by