Thyroid disorders and pregnancy

1. Thyroid disorders and pregnancy Medical Complications November 23, 2007 Jill Newstead-Angel, MD FRCPC

2. Objectives • Discuss the normal physiology of the thyroid gland during pregnancy • Discuss hyperthyroidism and pregnancy • Diagnosis • Treatment • Discuss hypothyroidism and pregnancy • Diagnosis • Treatment • Discuss thyroid nodules in pregnancy

3. Case 1 • 24 yr old G2P1 presents at 9 weeks GA for first prenatal visit • Part of screening blood work was TSH • TSH 0.5 mU/L • Clinically and on history - no evidence of thyroid disease

4. What should be done? • Book the patient for a radioactive iodine uptake scan • Start PTU at 100 mg bid • Do nothing at all • Check FT4 and FT3

5. Normal thyroid physiology in pregnancy • Fetal thyroid and fetal hypothalamic-pituitary-thyroid axis develop independently of maternal thyroid • Starts to function after 10 weeks GA • 11-12 weeks GA, fetal thyroid concentrates iodine and FT4 and TSH are present in fetal circulation

6. Increase in thyroid binding globulin due to increase in estrogen (stimulation of hepatic production and decreased degradation) • Increase in total T4 and T3 • Increase in GFR leads to increase in renal iodine clearance

7. HCG has similar properties to TSH therefore has intrinsic thyroid stimulating activity • increase FT4 and FT3 levels during first trimester

9. Increase frequency in goiters? • In iodine replete areas there is not an increased frequency of goiters during pregnancy • If there is a palpable goiter - should be further investigated as underlying thyroid disease is present 50% of the time

10. Hyperemesis Gravidarum • High levels of HCG • Associated biochemical evidence of hyperthyroidism • Does not need treatment • Follow patients out of first trimester to ensure not true hyperthyroidism

11. What should be done? • Book the patient for a radioactive iodine uptake scan • Start PTU at 100 mg bid • Do nothing at all • Check FT4 and FT3

12. Case 2 • 33 year old G5P4 presents at 13 weeks GA for first prenatal • Complaining of palpitations, heat intolerance, and tremors • Clinically: tachycardia, tremor and palpable thyroid with bruit

13. TSH <0.01 • FT4 33 • FT3 9

14. Hyperthyroidism and pregnancy • Prevalence 0.1 to 0.4% • Graves is the most common cause • Other causes: • Functioning adenoma • Toxic mutlinodular goiter • Thyroiditis • Excessive thyroid hormone intake • Gestational transient thyrotoxicosis

15. Diagnosis difficult in pregnancy because of the hyper dynamic state of pregnancy • Eye signs, tremor, weight loss, marked tachycardia more suggestive of hyperthyroidism • Laboratory • low TSH with elevated FT4 and FT3 • TSH receptor antibodies • TPO and TBG antibodies

16. Pregnancy outcome • Depends on treatment and control • Worse pregnancy outcomes with no treatment or partial treatment • Preterm labor • Preeclampsia • Stillbirth • Small for gestational age

17. Treatment • Antithyroid medications • PTU • partially inhibits the conversion of T4 to T3 • Crosses the placenta less • Dose 100 – 600 mg • Methimazole • Aplasia cutis • Dose 10 – 40 mg • Transient leukopenia develops 10% women treated • Beta blockers • Propranolol - may be useful in those with marked tachycardia

18. Surgery • Second trimester best • Reserved for those that fail medical treatment • Radioactive iodine treatment • Contraindicated in pregnancy • Over all goal • treat maternal disease while limiting potential for fetal hypothyroidism

20. Back to case • Send off blood work for Thyroid stimulating antibodies • Start PTU 100 mg tid • Start propanolol 10 - 20 mg bid • Repeat TSH in 2 weeks • Titrate medications to keep FT4 within higher limits of normal

21. Sub-clinical hyperthyroidism • Low TSH with normal FT4 • Affects 1.7% of pregnant women • During pregnancy – not found to be associated with any adverse outcomes

22. Case 3 • 25 year old G1P1 seen preconception for hypothyroidism • Would like to conceive in the near future • Currently on Synthyroid 75 mcg per day • Most recent TSH 4 with normal FT4 and FT3

23. Hypothyroidism and pregnancy • 95% the result of primary disease of the thyroid • Autoimmune (Hashimoto’s thyroiditis) • Less common causes • Over treatment of hyperthyroidism • Transient hypothyroidism due to postpartum thyroiditis • Medications • Pituitary or hypothalamic disease

24. Diagnosis • 20-30% of patients have symptoms • Elevated TSH • Patients with central hypothyroidism do not manifest elevated TSH during pregnancy

25. Complications • Overt hypothyroidism • Gestational hypertension (36% of patients • Placental abruption • Spontaneous abortion • Preterm birth • Postpartum hemorrhage

26. Association between maternal hypothyroidism and impaired cognitive function of the offspring

28. Thyroid replacement and medications • Drugs that interfere with absorption: • Prenatal vitamins • Iron replacement • Antacids • Cholestyramine • Drugs that interfere with metabolism • Phenytoin • Rifampin • Carbamazapine

29. Back to case • Increase her medication to 100 mcg per day to get her TSH <2.5 before conception • Once she becomes pregnant, check her TSH and adjust the dose as necessary • Monitor q trimester during pregnancy

30. Sub clinical hypothyroidism • Elevated TSH with ~normal FT4 and FT3 • Prevalence 4-8.5% • Pregnant women 2-5% • Normal TSH 0.3 and 2.5 mU/L • Levels between 2.5 and 4.0 “gray zone” • Values >4.0 indicative of early thyroid failure • Treat? • controversial

31. Postpartum Thyroiditis • Occurs in 5-10% of women • 25% of patients with DMI

32. Occurs 6-12 weeks postpartum • Phases • Hyperthyroid - last 1-2 months • Hypothyroid - last 6-9 months • Postpartum depression • Screen with a TSH as may be cause

33. Treatment • Hyperthyroid phase • Anti-thyroid medications not effective • Beta blockers for symptoms • Hypothyroid phase • Treat with replacement for 6-12 months and then reduce or discontinue dose and recheck TSH in 6 weeks

35. Thyroid nodules and cancer during pregnancy • Increase in the prevalence of thyroid nodule during pregnancy • Increase in the growth of existing nodules during pregnancy • No evidence to suggest thyroid cancer arises de novo more frequently during pregnancy

36. Evaluation • Lab evaluation of thyroid function • Ultrasound • FNA • Benign cytology - observe and follow postpartum • Malignant cytology - surgery recommended

37. Women with previously diagnosed or treated differentiated thyroid cancer require an increase in levothyroxine dosage during pregnancy • TSH of 0.1-0.8 mU/L for papillary or follicular cancer • TSH of <2.5 mU/L for patients with medullary thyroid cancer

38. Summary • Normal physiology of pregnancy is such that the TSH will decrease in the first trimester due to similarities to HCG • If initially low, repeat second trimester and check FT4 and FT3 • Hyperthyroidism - treat to maintain FT4 in the higher range of normal • Hypothyroidism - goal TSH 0.5 to 2.5 mU/L

39. Postpartum depression - screen for postpartum thyroiditis

40. Reference • Casey B, Leveno K. Thyroid disease in pregnancy. Obstetrics and Gynecology 2006; 108 (5): 1283-1292 • Hypothyroidism in the pregnant woman. Drug and therapeutic bulletin 2005; 44 (7): 53-55 • LeBeau S, Mandel S. Thyroid disorders during pregnancy. Endocrinology and Metabolism Clinics of North America. 2006; 35: 117-136 • Molitch M. Endocrine disease in pregnancy. Principles and Practice of Endocrinology and Metabolism 3rd edition.