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THYROID DISEASE IN PREGNANCY: TREATING TWO PATIENTS Susan J. Mandel, MD MPH Perelman School of Medicine, University of Pennsylvania Outline • Background • Importance of thyroid hormone during pregnancy • Hypothyroidism during pregnancy • General population of women in the child bearing years 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 The importance of thyroid hormone for normal growth and development 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 Sources of thyroid hormone for the fetus • Mom: Thyroid hormone crosses the placenta starting in 1st trimester • Fetus: Thyroid begins to function at 12 weeks gestation 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 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 What if the mom’s thyroid doesn’t work? ~2% of all pregnancies Subclinical Hypothyroidism Overt Spontaneous abortion5,7 10-70% 60% 1,2,4,6,9 Preeclampsia “Maternal hypothyroidism is 0-17% associated with 0-44% 2,3,4,6,7 increased rate of pregnancy complications, and Abruption 0% 0-19% the risk is greatest in overt hypothyroidism 1,2,3,6 Stillbirth/fetal loss 0-3% 0-12% compared to subclinical hypothyroidism.” LaFranchi, Thyroid 2005 Anemia2,3 0-2% 0-31% Postpartum hemorrhage2,3,4 0-17% 0-19% Preterm birth2,3,7,8 0-9% 20-31% 1Montoro et al, Ann Intern Med 1981; 2Davis et al, Obstet Gynecol 1988; 3Leung et al, Obstet Gynecol 1993; 4Wasserstrum et al, Clin Endocrinol 1993; 5Glinoer, Thyroid Today, 1995 6Allan et al, J Med Screen 2002; 7Abalovich et al, Thyroid 2002; 8Stagnaro-Green et al, Thyroid, 2005; 9Sahu et al, Arch Gynecol Obstet 2009 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 1st OB visit • TSH monitoring required during pregnancy One option: take two additional LT4 pills/week Yassa J Clin Endocrinol Metab 2010 95:3234 And, we are still not getting it right . . . Frequency (%) Abnormal thyroid function tests in pregnant hypothyroid women taking LT4 50 45 40 35 30 25 20 15 10 5 0 43 33 28 1st trimester n=389 McClain, Am J Obstet Gynecol 2008 2nd trimester Both trimesters 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 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 iodine • Measured iodine content was only 75% of labeled content! Leung A et al N Engl J Med 2009 360:9 2011 Guidelines: Endocrine Society American Thyroid Association • All women attempting to conceive and pregnant women take a prenatal vitamin containing 150mcg of potassium iodine Screening • Prevalent disease • Screening test for disease identification • Adverse outcome related to disease • Therapy that ameliorates outcome 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 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. 14th International Thyroid Congress, Sept 2010 Maternal Adverse Outcomes: Negro 2010 PRIMARY ENDPOINT: NO BENEFIT to pregnancy outcome complications/patient 2 1.5 1 0.7 0.7 0.5 0 Universal Screen Case Finding Cognitive Development: Cognitive development and Maternal Hypothyroidism CATS 2010 PRIMARY ENDPOINT: NO difference in IQ scores 120 IQ score 100 80 100 99 60 40 20 0 Universal Screen Courtesy of John Lazarus ITC 2010 Control • However, secondary analyses for both studies suggest a benefit • Negative results could be due to screening and intervention at end of 1st trimester— TOO LATE What to do 2011 Guidelines: Endocrine Society American Thyroid Association • Insufficient evidence to recommend universal screening for thyroid disease in pregnant women • Aggressive detection of women at high risk for thyroid dysfunction 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 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 Thank you for your attention