1. Thyroid Disease in Pregnancy District 1 ACOG Medical Student Teaching Module 2011

2. Physiologic Changes in Thyroid Function During Pregnancy • Thyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesis • The test results that change in pregnancy are influenced by changes in TBG concentration • Plasma iodide levels decrease due to fetal iodide use and increased maternal clearance -> leads to notable increase in gland size in 15% of women (without abnormal TFTs)

3. Physiologic Changes in Thyroid Function During Pregnancy

4. The Fetal Thyroid • Begins concentrating iodine at 10-12 weeks • Controlled by pituitary TSH by approximately 20 weeks

5. Hyperthyroidism Look for: -Nervousness -Tremor -Tachycardia -Frequent stools -Sweating -Heat intolerance -Weight loss -Goiter -Insomnia -Palpitations -Hypertension -Lid lag/lid retraction -Pretibial myxedema • Occurs in 0.2% of pregnancies; Graves’ disease accounts for 95% of cases

6. Fetal & Neonatal Effects of Hyperthyroidism • Associated with preterm delivery, low birth weight, fetal loss • Fetal thyrotoxicosis (related to disease itself or treatment) • Risk of immune-mediated hypo/hyperthyroidism (due to antibodies crossing the placenta, esp. in Graves or chronic autoimmune thyroiditis) • Antibodies in Graves’ disease can be either stimulatory or inhibitory • Neonates of women with Graves’ who have been surgically/radioactively treated are at higher risk, b/c not taking suppression

7. Causes & Diagnosis of Hyperthyroidism • Most common cause of hyperthyroidism is Graves’ disease • Document elevated FT4 or elevated FTI with suppressed TSH, in absence of goiter/mass • Most patients have antibodies to TSH receptor, antimicrosomal, or antithyroid peroxidase antibodies, but measurement of these is not required (though some endocrinologists recommend measuring TSI, which are stimulatory antibodies to TSH receptor) • Other causes: • Excess TSH production, gestational trophoplastic disease, hyperfunctioning thyroid adenoma, toxic goiter, subacute thyroiditis, extrathyroid source of TH

8. Treatment of Hyperthyroidism • Goal is to maintain FT4/FTI in high normal range using lowest possible dose (minimize fetal exposure) • Measure FT4/FTI q2-4 weeks and titrate • Thioamides (PTU/methimazole) -> decrease thyroid hormone synthesis by blocking organification of iodide • PTU also reduces T4->T3 and may work more quickly • PTU traditionally preferred (older studies found that methimazole crossed placenta more readily and was associated with fetal aplasia cutis; newer studies refute this)

9. Treatment of Hyperthyroidism • Effect of treatment on fetal thyroid function: • Possible transient suppression of thyroid function • Fetal goiter associated with Graves’ (usually drug-induced fetal hypothyroidism) • Fetal thyrotoxicosis due to maternal antibodies is rare -> screen for growth and normal FHR • Neonate at risk for thyroid dysfunction; notify pediatrician • Breastfeeding safe when taking PTU/methimazole

10. Treatment of Hyperthyroidism • Beta-blockers can be used for symptomatic relief (usually Propanolol) • Reserve thyroidectomy for women in whom thioamide treatment unsuccessful • Iodine 131 contraindicated (risk of fetal thyroid ablation especially if exposed after 10 weeks); avoid pregnancy/breastfeeding for 4 months after radioactive ablation

11. Hypothyroidism • Symptoms: fatigue, constipation, cold intolerance, muscle cramps, hair loss, dry skin, slow reflexes, weight gain, intellectual slowness, voice changes, insomnia • Can progress to myxedema and coma • Subclinical hypothyroidism: elevated TSH, normal FTI in asymptomatic patient • Associated with other autoimmune disorders • Type 1 DM -> 5-8% risk of hypothyroidism; 25% postpartum thyroid dysfunction

12. Hypothyroidism: Fetal & Neonatal Effects • Higher incidence of LBW (due to medically indicated preterm delivery, pre-eclampsia, abruption) • Iodine deficient hypothyroidism -> congenital cretinism (growth failure, mental retardation, other neuropsychological deficits)

13. Causes & Diagnosis of Hypothyroidism • Causes: • Hashimoto’s (chronic thyroiditis; most common in developed countries) & iodine deficiency -> both associated with goiter • Subacute thyroiditis -> not associated with goiter • Thyroidectomy, radioactive iodine treatment • Iodine deficiency (most common worldwide; rare in US)

14. Treatment of Hypothyroidism • Treat with Levothyroxine in sufficient dose to return TSH to normal • Adjust dosage every 4 weeks • Check TSH every trimester

15. ACOG Recommendations • Screening of all pregnant women with a personal history, physical examination, or symptoms of a thyroid disorder.

16. Prolog Question #1 • A 33 year-old G3 P2 at 10 weeks GA comes to the office for her 1st prenatal visit. She reports that she had hypothyroidism in the distant past, but was never treated and is asymptomatic. Physical examination is normal. On bimanual examination her uterus is 10 weeks size and FHR is 150 bpm. Her TSH level is 13.1 and, free T4 level is 0.7, and her anti-thyroid peroxidase antibody level is high. The next best step in the patient’s care is: • A) Begin levothyroxine • B) Repeat serum TSH and Free T4 after 20 weeks of gestation • C) Measure serum thyroid-stimulating immunoglobulins • D) Perform ultrasonography of the maternal thyroid

17. Answer • A) Begin levothyroxine • Although the patient is asymptomatic she has laboratory evidence of overt hypothyroidism with an elevated TSH and low free T4 level • She also has elevated anti-thyroid peroxidase antibody level which indicates that the likely cause of her hypothyroidism is chronic autoimmune thyroditis (Hashimoto’s disease) • The anti-thyroid peroxidase antibodies also indicate an increased risk of her developing other autoimmune disease, such as adrena insufficiency or type 1 DM. • Hypothyroidism in pregnancy has been associated with pre-eclampsia, GHTN, abruptio placentae, preterm delivery, and neuropsychologic deficits in the child.