2. THYROID DISEASE IN PREGNANCY: TREATING TWO PATIENTS Susan J. Mandel, MD MPH Perelman School of Medicine, University of Pennsylvania

3. Outline Background Importance of thyroid hormone during pregnancy Hypothyroidism during pregnancy General population of women in the child bearing years

4. Thyroid gland Thyroid hormones—made from IODINE –Thyroxine (T4) –Triiodothyronine (T3) MOSTLY made in liver Many targets in the human body Synthetic T4 (LEVOTHYROXINE LT4) readily available

5. The importance of thyroid hormone for normal growth and development

7. Cretinism Due to severe dietary iodine deficiency Severe hypothyroidism in BOTH Mom and fetus Impaired cognitive development Poor growth Iodine deficiency is considered the most common cause of preventable brain damage in the world today (WHO 1994). http://www.thyroidmanager.org/Chapter20/index.html

8. Sources of thyroid hormone for the fetus Mom: Thyroid hormone crosses the placenta starting in 1 st trimester Fetus: Thyroid begins to function at 12 weeks gestation

9. And if the baby’s thyroid doesn’t work.... Congenital hypothyroidism affects 1:3000 live births in the US Newborn screening programs in all 50 states Detection and treatment by 1 month of life results in normal outcomes THEREFORE, maternal thyroid hormone can protect fetal development in utero

10. What if the mom’s thyroid doesn’t work? “Hypothyroidism” –Hashimoto’s thyroiditis –Prior ablation with radioactive iodine –Prior thyroid surgery Detected by a blood test (TSH) Spectrum –Mild “subclinical” hypothyroidism 1:50 pregnancies –Severe “overt” hypothyroidism 1:500 pregnancies

11. SubclinicalOvert Hypothyroidism Spontaneous abortion 5,7 10-70%60% Preeclampsia 1,2,4,6,9 0-17%0-44% Abruption 2,3,4,6,7 0%0-19% Stillbirth/fetal loss 1,2,3,6 0-3%0-12% Anemia 2,3 0-2%0-31% Postpartum hemorrhage 2,3,4 0-17%0-19% Preterm birth 2,3,7,8 0-9%20-31% 1 Montoro et al, Ann Intern Med 1981; 2 Davis et al, Obstet Gynecol 1988; 3 Leung et al, Obstet Gynecol 1993; 4 Wasserstrum et al, Clin Endocrinol 1993; 5 Glinoer, Thyroid Today, 1995 6 Allan et al, J Med Screen 2002; 7 Abalovich et al, Thyroid 2002; 8 Stagnaro-Green et al, Thyroid, 2005; 9 Sahu et al, Arch Gynecol Obstet 2009 “Maternal hypothyroidism is associated with increased rate of pregnancy complications, and the risk is greatest in overt hypothyroidism compared to subclinical hypothyroidism.” “Maternal hypothyroidism is associated with increased rate of pregnancy complications, and the risk is greatest in overt hypothyroidism compared to subclinical hypothyroidism.” LaFranchi, Thyroid 2005 What if the mom’s thyroid doesn’t work? ~2% of all pregnancies

12. For hypothyroid women taking levothyroxine (LT4) who become pregnant Increased LT4 dosage required in majority of woman Average dose increase about 30% TIMING for increase as early at 7-8 weeks gestation USUALLY prior to 1 st OB visit TSH monitoring required during pregnancy One option: take two additional LT4 pills/week Yassa J Clin Endocrinol Metab 2010 95:3234

13. And, we are still not getting it right... Abnormal thyroid function tests in pregnant hypothyroid women taking LT4 McClain, Am J Obstet Gynecol 2008 n=389

14. 2011 Guidelines: Endocrine Society American Thyroid Association Pre conception education of hypothyroid women and optimization of LT4 dosage Check thyroid function tests as soon as pregnancy confirmed and consider empirically increasing LT4 dose by taking 2 additional LT4 tablets per week

15. Thyroid health in pregnant women without thyroid disease Daily iodine requirements increase in pregnancy –WHO 250mcg/day –Institute of Medicine 220mcg/day NOT all prenatal vitamins contain iodine! In the USA, as of 2009, only 51% of prenatal vitamins labeled to contain iodineIn the USA, as of 2009, only 51% of prenatal vitamins labeled to contain iodine Measured iodine content was only 75% of labeled content!Measured iodine content was only 75% of labeled content! Leung A et al N Engl J Med 2009 360:9

16. All women attempting to conceive and pregnant women take a prenatal vitamin containing 150mcg of potassium iodine 2011 Guidelines: Endocrine Society American Thyroid Association

17. Screening Prevalent disease Screening test for disease identification Adverse outcome related to disease Therapy that ameliorates outcome

18. Screening: Thyroid disease in pregnancy Prevalent disease –YES--~2% of all pregnancies Screening test for disease identification –YES Adverse outcome related to disease –YES Therapy that ameliorates outcome –Therapy —YES –Outcome improved — so far NO

19. Recent Developments for Subclinical Hypothyroidism 2 prospective randomized controlled trials MATERNAL HEALTH Negro R et al, Universal Screening vs Case Finding for Detection and Treatment of Thyroid Dysfunction During Pregnancy, J Clin Endocrinol Metabolism 2010 95:1699 FETAL HEALTH Lazarus J et al. Controlled Antenatal Thyroid Screening (CATS) Study. 14 th International Thyroid Congress, Sept 2010

20. Maternal Adverse Outcomes: Negro 2010 PRIMARY ENDPOINT: NO BENEFIT to pregnancy outcome

21. Cognitive development and Maternal Hypothyroidism Courtesy of John Lazarus ITC 2010 Cognitive Development: CATS 2010 PRIMARY ENDPOINT: NO difference in IQ scores

22. What to do However, secondary analyses for both studies suggest a benefit Negative results could be due to screening and intervention at end of 1 st trimester— TOO LATE

23. Insufficient evidence to recommend universal screening for thyroid disease in pregnant women Aggressive detection of women at high risk for thyroid dysfunction 2011 Guidelines: Endocrine Society American Thyroid Association

24. Women at risk for hypothyroidism History of thyroid dysfunction or prior thyroid surgery Signs or symptoms of thyroid problem Women older than age 30 Presence of other autoimmune disorders –Type 1 diabetes, rheumatoid arthritis Family history of thyroid dysfunction History of miscarriage or preterm labor

25. What is needed... Education programs targeted to patients and care providers –HYPOTHYROID PREGNANT patients: HIGHER thyroid hormone doses –All women: IODINE containing prenatal vitamins Partnerships with public health, government and professional organizations to insure all prenatal vitamins contain 150mcg of potassium iodine Exploration of the feasibility of a randomized controlled trial that screens, identifies, and treats thyroid dysfunction in women PRIOR to conception

26. Thank you for your attention