1. 관동의대 제일병원 내과 임창훈 갑상선질환과 임신

2. 임신  갑상선의 변화 (physiologic, immunologic) 임신  갑상선기능항진증 / 저하증 산후 갑상선기능이상

3. Regulation of Thyroid Function in Normal Pregnancy increased TBG high Estrogen transient decreased free Hormones increased TSH (within normal limits) high hCG (thyrotropic activity of hCG) stimulation of maternal Thyroid modification in the peripheral metabolism of thyroid hormones through transplacental passage & deiodination Surks MI, Atlas of Clinical Endocrinology. 1999

4. Thyroid Stimulation The Iodine environment - daily iodine intake - pre-existing intrathyroidal iodine stores - renal losses (clearance inc.) - diversion to feto-placental unit in iodine deficiency “pathological alterations” - relative hypo T4 - goitrogenic stimulus (mother and child) in iodine sufficiency “pathological adaptation” - no relative hypo T4 - no goitrogenesis definitive Pathological changes Endocr Rev 1997:8:404

5. The pattern of changes in thyroid function and hCG Clinical Obstetrics and Gynecology 1997 ; 40:6 010203040 Weeks of Gestation TBG hCG total T4 free T4 TSH

6. Immune change in pregnancy and postpartum PregnancyPostpartum T cellsReduced Th1 T cell activityEnhanced Th1 T cell function Maternal tolerance for fetal alloAgs Loss of tolerance for fetal alloAg B cellsB cell function reducedTotal IgG secretion enhanced AutoAb secretion reducedAutoAb secretion enhanced Thyroid 1999 ; 9:677

7. Placental transfer of thyroid hormone and agent Placental transferLimited-transferNot transfer Iodide.T3TSH PTU, MMZT4thyroglobulin beta-blocker IgG (TSI, …) TRH

8. Hypothyroidism and Pregnancy

9. Prevalence of maternal hypothyroidism 0.3-0.5% for overt hypothyroidism 2-3% for subclinical hypothyroidism

10. Pregnancy complication reported in hypothyroid women MaternalFetal Gestational hypertensionSpontaneous abortion PreeclamsiaSmall for gestational age PIHFetal stress during labor AnemiaFetal death Postpartum hemorrhageTransient congenital hypothyroidism due to transplacental passage of maternal TSH-blocking Ab Placental abruptionPossible impairment in cognitive function

11. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. (Haddow JE, et al. N Engl J Med. 1999:341:549)

12. Maternal hypothyroidism should be avoided. Targeted case finding is recommended at the first prenatal visit. Recommend adjustment of the preconception T4 dose to reach a TSH < 2.5 mU/L. Recommends T4 replacement in women with subclinical hypothyroidism.

13. The T4 dose usually needs to be incremented by 4–6wk gestation and may require a 30–50% increase. The T4 dosage should be titrated to rapidly reach and thereafter maintain serum TSH conc. < 2.5 mU/L in the first trimester. After delivery, decrease in the T4 dosage.

14. T3, T4 정상 TSH 정상 TPO Ab (+)

15. Euthyroidism with Autoimmune thyroid disease - normal TFT, thyroperoxidase Ab(+), thyroglobulin ab(+) - lack of thyroid reserve in response to the stimulatory effect of pregnancy - increased risk for several pregnancy-related Cx (spontaneous miscarriage, subclinical hypothyroidism, and postpartum thyroiditis) - should be monitored for elevation of TSH.

16. Hyperthyroidism and Pregnancy

17. Prevalence: 0.1-0.4% Decrease in antithyroid therapy after 24-28wks gestation Use the minimum amount of ATD to keep free T4 levels in the upper third of normal

18. Complication for untreated or poorly controlled hyperthyroidism Maternal Miscarriage PIH Preterm delivery CHF Thyroid storm Placenta abruptio Fetal LBW Prematurity Small-for-gestational age IUR Goiter Hypothyroidism Stillbirth Hyperthyroidism

19. DDx between Gestational and Graves’ hyperthyroidism GestationalGraves’ Sx pre-pregnancy-++ Sx during pregnancy-/++/+++ Nausea/vomiting+++-/+ Goiter/Ophthalmopathy-+ Thyroid Ab-+

20. Anti-thyroid drug PTU used as a first-line drug, especially during first-trimester organogenesis. Methimazole may be prescribed if PTU is not available No evidence that Tx of subclinical hyperthyroidism improves pregnancy outcome

21. Surgery may be indicated during pregnancy 1) a severe adverse reaction to ATD therapy, 2) persistently high doses of ATD are required, 3) uncontrolled hyperthyroidism. The optimal timing of surgery is in the second trimester. 131I should not be given to pregnant woman.

22. The Postpartum Recurrence of Graves' Disease and Its Contributing Factors Thyroid Function Change after Delivery Thyroid functionNo of patients Euthyroid Postpartum thyroiditis GD (Recurrence) 61 (69.3%) 13 (14.8%) 14 (15.9%)

23. Hyperthyroidism TSAb(+) ATD Maternal GD Tx with ATD Maternal & Fetal thyroid function stimulation by Thyroid Stimulating Ab inhibition by Antithyroid drug Maternal thyroid function serves as a " Biosensor" that reflects Fetal thyroid

24. Hyperthyroidism TSAb(+) T4 Maternal hypothyroid Tx with T4 (after RAITx or thyroidectomy for GD) Maternal thyroid function does not serves as a " Biosensor" that reflects Fetal thyroid Fetal US should be performed to look for evidence of fetal thyroid dysfunction fetal hyperthyroidism

25. Thyroid nodule and Cancer Fine-needle aspiration (FNA) cytology should be performed for thyroid nodules larger than 1 cm discovered in pregnancy. When nodules are discovered to be malignant, pregnancy should not be interrupted, but surgery should be offered in 2nd trimester. 131I should not be given to women who are breastfeeding.

26. Postpartum Thyroid dysfunction

27. Various types of postpartum thyroid dysfunction Delivery Thyroid function 64 months2 Transient hypothyroidism Destructive thyrotoxicosis (Amino et al, 1999 )

28. Thyroid peroxidase Ab (+) women should have a TSH performed at 3 and 6 months postpartum. Women with a history of PPT have a risk of developing permanent hypothyroidism. Sx(-) women with PPT (N < TSH < 10 mU/L) and who are not planning a subsequent pregnancy do not necessarily require intervention but should be remonitored in 4–8 wk. Sx(+) women and women with a TSH above normal and who are attempting pregnancy should be treated with levothyroxine.

29. Various types of postabortional thyroid dysfunction Abortion Thyroid function 8 3 2 17 4 months2

30. SCREENING FOR THYROID DYSFUNCTION DURING PREGNANCY Hx of thyroid disease. FHx of thyroid disease. With a goiter. With thyroid antibodies. With Sx or Sign of thyroid dysfunction With type I diabetes. With other autoimmune disorders. With infertility PMHx of head or neck irradiation. Hx of miscarriage or preterm delivery.