임신 중 갑상선 질환의 관리- 임창훈 교수

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임신 중 갑상선 질환의 관리- 임창훈 교수

임신 중 갑상선 질환의 관리- 임창훈 교수

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  • 1. 임신 중 갑상선질환의 관리 관동의대 제일병원 내과 임창훈
  • 2. 임신시 갑상선질환의 빈도2010년 7010명 산모에서,초진시 병력상 갑상선질환 있었던 경우는 326명. (제일병원 산모인덱스 2010) 치료 중 180 2.6 기능저하증 123 1.8 기능항진증 37 0.5 갑상선암 20 0.3 과거 치료 146 2.1 기능저하증 11 0.2 기능항진증 29 0.4 갑상선결절 36 0.5 갑상선질환 (진단 모름) 70 1.0 전체 326명 4.7%
  • 3. (J Clin Endocrinol Metab 2007) (Thyroid 2011)(J Clin Endocrinol Metab 2012)
  • 4. Normal TSH in pregnancy
  • 5. The pattern of changes in thyroid function and hCG TBG total T4 hCG TSH free T4 0 10 20 30 40 Weeks of Gestation Clinical Obstetrics and Gynecology 1997
  • 6. What is the normal range for TSH in eachtrimester?Recommended reference range for TSH (I) 1st trimester : 0.1–2.5 mIU/L 2nd : 0.2–3.0 3rd : 0.3–3.0
  • 7. Sample Trimester-Specific Reference Intervals for Serum TSH TrimesterReference First Second ThirdHaddow et al. 0.94 (0.08-2.73) 1.29 (0.39-2.70)Stricker et al. 1.04 (0.09-2.83) 1.02 (0.20-2.79) 1.14 (0.31-2.90)Panesar et al. 0.8 (0.03-2.30) 1.1 (0.03-3.10) 1.3 (0.13-3.50)Soldin et al. 0.98 (0.24-2.99) 1.09 (0.46-2.95) 1.2 (0.43-2.78)Bocos-Terraz et al. 0.92 (0.03-2.65) 1.12 (0.12-2.64) 1.29 (0.23-3.56)Marwaha et al. 2.10 (0.60-5.00) 2.4 (0.43-5.78) 2.1 (0.74-5.70) (Thyroid 2012)
  • 8. Gestational week-specific TSH values percentile weeks number % 5 median 95 5 55 6.3 0.76 2.20 4.61 6 155 17.6 0.30 2.10 5.40 7 265 30.1 0.20 1.60 4.17 8 168 19.1 0.11 1.28 3.64 9 125 14.2 0.10 1.10 3.57 10 65 7.4 0.03 0.95 3.85 11 22 2.5 0.01 0.85 2.92 12 24 2.7 0.01 1.10 4.38 total 879 100 0.10 1.50 4.20 (제일병원 산모인덱스 2010)
  • 9. (제일병원 산모인덱스 2010) NumbersTSH Gestational weeks Gestational weeks
  • 10. (제일병원 산모인덱스 2010) NumbersTSH Gestational weeks Gestational weeks
  • 11. Gestational week-specific TSH values G weeks numbers median G weeks numbers median 5 55 2.2 6 155 2.1 7 265 1.6 8 168 1.28 8 240 1.06 9 125 1.1 9 312 1.03 10 65 0.95 10 247 0.93 11 22 0.85 11 178 1.0 12 24 1.1 12 110 1.1 13 39 1.06 total 879 1.5 total 1126 1.0 (제일병원 산모인덱스 2010) (Haddow JE, 2004)
  • 12. Gestational week-specific TSH values G weeks numbers median G weeks numbers median 5 55 2.2 6 155 2.1 7 265 1.6 8 168 1.28 8 240 1.06 9 125 1.1 9 312 1.03 10 65 0.95 10 247 0.93 11 22 0.85 11 178 1.0 12 24 1.1 12 110 1.1 13 39 1.06 total 879 1.5 total 1126 1.0 (제일병원 산모인덱스 2010) (Haddow JE, 2004)
  • 13. Hypothyroidism in pregnancy
  • 14. Maternal hypothyroidismMaternal FetalGestational hypertension Spontaneous abortion Preeclamsia Small for gestational age PIH Fetal stress during laborAnemia Fetal deathPostpartum hemorrhage Transient congenital hypothyroidismPlacental abruption Possible impairment in cognitive functionMaternal hyperthyroidismMaternal FetalMiscarriage LBW (Prematurity, Small-for-gestational age,PIH IUGR)Preterm delivery GoiterCHF HypothyroidismThyroid storm StillbirthPlacenta abruptio Hyperthyroidism Best Pract Res Clin Endocrinol Metab. 2004
  • 15. 임신 중 약물의 태반 통과 (모체) (태반) (태아)항갑상선제 갑상선기능저하증 유발요오드 태아에 요오드 공급갑상선 자극항체 갑상선기능항진증갑상선호르몬 뇌조직 성장 (임신초기)
  • 16. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. (Haddow JE, N Engl J Med 1999) 62/25,000 children Children of Children of Control treated women untreated women with hypothyroidism with hypothyroidismNumber 14 48 124IQ score 111 100 107p-score 0.20 0.005
  • 17. Should overt hypothyroidism be treated inpregnancy?Overt hypothyroidism (OH): TSH > 2.5 mIU/L with fT4 or TSH ≥ 10 mIU/LOH should be treated in pregnancy.
  • 18. Subclinical hypothyroidism (SCH): TSH 2.5~10 mIU/L with normal FT4SCH associate with adverse maternal and fetal outcomes.TPOAb(+) & SCH pregnant women should be treated with LT4.Universal LT4 treatment in TPOAb(-) & SCH pregnant women (I)
  • 19. What is the goal of treatment?To normalize TSH within the trimester-specific pregnancy reference range. (A) 1st trimester : 0.1–2.5 mIU/L 2nd : 0.2–3.0 3rd : 0.3–3.0
  • 20. How do treated hypothyroid women differfrom other patients during pregnancy?In women with known hypothyroidism, hCG and TSH can not stimulate T4 production.Treated hypothyroid patients should increase their dose of LT4 by 25%–30% on positive pregnancy test.
  • 21. Hyperthyroidism in pregnancy
  • 22. What is the management of patients withGraves’ hyperthyroidism in pregnancy?(Guideline 2007)PTU should be used as a 1st -line drug.MMI may produce aplasia cutis, choanal or esophageal atresia and dysmorphic facies.FDA called attention to the risk of hepatotoxicity of PTU.
  • 23. PTU is preferred in 1st trimester. (I)Following 1st trimester, consideration should be given to switching to MMI. (I)(in lactating women?)MMI (< 20–30 mg/d) is safe. (A)PTU (<300mg/d) is 2nd -line agent due to concerns about severe hepatotoxicity. (A)
  • 24. How can gestational hyperthyroidism bedifferentiated from Graves’ hyperthyroidismin pregnancy? Gestational Graves’Sx pre-pregnancy - ++Sx during pregnancy -/+ +/+++Nausea/vomiting +++ -/+Goiter/Ophthalmopathy - +TSH Receptor Ab - + Best Pract Res Clin Endocrinol Metab. 2004
  • 25. Thyroid AutoAb (+)Association between TAb and spontaneous abortionLT4 therapy in TAb+ euthyroid women decreased abortion rate.Insufficient evidence to recommend for or against screening for TAb or LT4 therapy in TAb+ euthyroid women. (I)
  • 26. Thyroid nodules in pregnancy
  • 27. Prevalence of thyroid nodule detected by US in thewomen for health check-up (Yim, 2002) Age n Subjects with nodules (%) 30-39 117 36 (30.8) 40-49 960 355 (37.0) 50-59 200 83 (41.5) 60-69 23 15 (65.2)
  • 28. FNA confers no additional risks to a pregnancy.Thyroid nodules discovered during pregnancy that have suspicious ultrasound features should be considered for FNA. (I)
  • 29. (2007 Guideline)When nodules are discovered to be malignant, surgery should be offered in the 2nd trimester.Because the prognosis of women with well- differentiated thyroid cancer (DTC) identified but not Tx during pregnancy is similar to that of nonpregnant patients, surgery may be generally deferred until postpartum. (B)
  • 30. Postpartum thyroid dysfunction
  • 31. Immunity in pregnancy Hashimoto’s thyroiditis Graves’ disease activation Immune activity Cellular Humoral immunity immunity pregnant 3 6 9 12 Postpartum (months) Delivery suppression Thyroid 1999;9:710
  • 32. 임상양상 Persistent thyrotoxicosisThyroid function Transient thyrotoxicosis 2 4 months 6 Transient hypothyroidism Delivery Persistent hypothyroidism (Amino et al, 1999)
  • 33. 산후 갑상선기능장애 (Postpartum thyroid dysfunction) = Postpartum thyroiditis (Destructive thyrotoxicosis)Thyroid function 2 4 months 6 PPT Delivery (Transient hypothyroidism)
  • 34. 산후 갑상선기능장애 (Postpartum thyroid dysfunction) = Postpartum thyroiditis + Postpartum Graves’ disease (Destructive thyrotoxicosis) Graves’ dis.Thyroid function 2 4 months 6 PPT Delivery (Transient hypothyroidism)
  • 35. Thyroid function TSH 감소 T3, T4 증가
  • 36. Delivery, Abortion (?) Thyroid function 2 4 mo
  • 37. Delivery, Abortion (?) TSH R Ab (+) Thyroid function 2 4 mo TSH R Ab (-)
  • 38. What is the treatment for postpartumthyroiditis (PPT)?During thyrotoxic phase, symptomatic women may be treated with beta blockers. (B)TSH should be tested every 2 months until 1 year postpartum. (B)Women who are hypothyroid with PPT and attempting pregnancy should be treated with LT4. (A) (or if severe Sx or if patient desires Tx)
  • 39. (Guideline 2007)Asymptomatic women with PPT who have a TSH < 10 mIU/L and who are not planning a subsequent pregnancy do not necessarily require intervention. (B)Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be treated with LT4. (B)
  • 40. Iodine and pregnancy
  • 41. Pregnant and lactating women should ingest a minimum of 250 ug/d iodine. (A)Sustained iodine intake (>500–1100 ug/d) should be avoided due to concerns about the potential for fetal hypothyroidism. (C)
  • 42. Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk supply J Paediatr Child Health, 2011 Female baby was born at 36 weeks by normal delivery weighing 2.66 kg. TSH was normal on day three of life. TSH 39 mIU/L (0.4–5.0) & fT4 9.7 pmol/L (13–30) at three weeks of age. The mother of the baby was Korean, her main food for several weeks was seaweed soup.
  • 43. Iodine content of human milk and dietary iodineintake of Korean lactating mothers Int J Food Sci Nutr 1999 Iodine values of human milk for different intakes of seaweed soup Stage of Frequency of Dietary iodine Iodine content lactation seaweed soup intake (ug/day) in human milk intake (%) (ug/L) 2-5 days p.p. 1-2 (6.2) 1667.7 1223 3 (54.2) 2503.3 2063 4+ (39.6) 3242.8 2466 4 weeks p.p. 0 (25.6) 260.0 185 1 (20.5) 723.6 272 2 (30.8) 1896.9 1370 3+ (23.1) 2273.0 1590
  • 44. Subclinical hypothyroidism in Korean preterm infantsassociated with high levels of iodine in breast milk J Clin Endocrinol Metab 2009
  • 45. High Iodine Content of Korean Seaweed Soup:A Health Risk for Lactating Women and Their Infants? Thyroid , 2011 The mean iodine content of blended seaweed soup contents was 1705±930 ug/250 mL. Iodine intake of at least 5000 ug/day in the first postpartum week (based on 250mL seaweed soup broth three times daily).
  • 46. Prevalence of Postpartum thyroid dysfunction (Thyroid 1999) Year Autbor Country Prevalence(%) 1982 Amino Japan 5.5 1982 Turney USA 9 1984 Jansson Sweden 6.5 1985 Walfish Canada 7.1 1986 Freeman USA 1.9 1987 Nikolai USA 6.7 1987 Lervang Denmark 3.9 1988 Fung UK 16.7 1990 Rasmussen Denmark 3.3 1990 Rajatanavin Thailand 1.1 1991 Roti Italy 8.7 1991 Lobig Germany 2 1992 Walfish Canada 6 1992 Stagnaro-Green USA 8.8 1992 Kannan India 7 1996 Pizarro Spain 9.3 1997 Yim Korea 8
  • 47. PPT was occurred in 10.3%(6/58) postparturm women.No correlation between pre and post-partum dietary iodine intake and occurrence of PPT (Cho YW, J Korean Soc Endocrinol, 1997)PPT developed in 8.1%(8/99) of postpartum women.Duration of high iodine intake, total ingested amount of high iodine diet, the urinary iodine excretion at 1 month postpartum were not different between two groups. (Kim WB, J Kor Soc Endocrinol, 1998)
  • 48. 한국으로 시집 온 H 씨(23)는 첫 아이를 출산한후 시어머니가 끓여주는 미역국만 억지로 먹어야 했다. 몽골에선 해산 후 양고기를 먹지만 한국에선 삼시 세 끼 미역국만 먹어 고생을 했다는‘몽골 새댁’도 있었다. (다문화사회의 동반자, 이주여성)
  • 49. Universal TSH screeening / Case-finding approach in pregnancy
  • 50. There is insufficient evidence to recommend for or against universal TSH screening at the first trimester visit. (I)All pregnant women should be verbally screened at the initial prenatal visit for history of thyroid dysfunction or medications. (B)
  • 51. TSH screening early in pregnancy in thefollowing women (B)Hx of thyroid dysfunction or surgeryAge >30 yearsSx of thyroid dysfunction or the presence of goiterTPOAb positivityT1DM or other autoimmune disordersHx of miscarriage or preterm deliveryHx of head or neck radiationFHx of thyroid dysfunctionMorbid obesity (BMI ≥ 40 kg/m2)Use of amiodarone or iodinated radiologic contrastInfertilityResiding in an area of iodine insufficiency
  • 52. BUT30% of hypothyroid women would not have been identified using the case-finding approach. (Vaidya B, J Clin Endocrinol Metab, 2005)55% of women with thyroid abnormalities would have been missed using a case-finding rather than a universal screening. (Horacek J, Eur J Endocrinol, 2010)
  • 53. (in Cheil Hospital)in 291 first trimester women, TPO-Ab (+) 33 / 291 (11.3%) TPO-Ab (+) with subclinical hypothyroidism 10 / 291 (3.4%) Hx of thyroid dysfx. or Tx (+) 4 / 10 (-) 6 / 10Universal screening in the first trimester of AITD is cost- effective, not only compared with no screening but also compared with sccreeing of high-risk women. (Dosiou C, J Clin Endocrinol Metab, 2012)