2014 07 01 universal thyroid screening

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2014 07 01 universal thyroid screening

  1. 1. Chang Hoon Yim Kwandong University Cheil General Hospital Endocrine Controversy in Pregnancy: Thyroid screening in pregnant women
  2. 2. Maternal hypothyroidism Maternal Fetal Gestational hypertension Spontaneous abortion Preeclamsia Small for gestational age PIH Fetal stress during labor Anemia Fetal death Postpartum hemorrhage Transient congenital hypothyroidism Placental abruption Possible impairment in cognitive function Best Pract Res Clin Endocrinol Metab. 2004 Maternal Fetal Miscarriage LBW (Prematurity, Small-for-gestational age, IUGR)PIH Preterm delivery Goiter CHF Hypothyroidism Thyroid storm Stillbirth Placenta abruptio Hyperthyroidism Maternal hyperthyroidism
  3. 3. Screening for thyroid disease during pregnancy depends on Is disease common during pregnancy? Does disease have adverse maternal /fetal effects? Is there a safe, inexpensive, & universally available test? Does therapeutic interventions exist? Is screening and intervention cost-effective?
  4. 4. Prevalence of thyroid dysfunction in pregnant women 0.3 – 0.5% Overt hypothyroidism 2 – 2.5% Subclinical hypothyroidism (SCH) 0.1 – 0.4% Overt Hyperthyroidism
  5. 5. 산모 과거력상 갑상선질환의 빈도 비교 2009년 6353명에서 314명 (4.9%) 2010년 7010명에서 326명 (4.7%) (제일병원산모인덱스 2009, 2010) 2009년 2010년 치료중 기능저하증 69 1.1% 123 1.8% 기능항진증 28 0.4% 37 0.5% 갑상선암 15 0.2% 20 0.3% 과거치료 기능저하증 44 0.7% 11 0.2% 기능항진증 39 0.6% 29 0.4% 갑상선결절 26 0.4% 36 0.5% 갑상선질환 (진단 모름) 93 1.5% 70 1.0% 314명 4.9% 326명 4.7%
  6. 6. Serum TSH testing is inexpensive, is widely available, and is a reliable test. Trimester-specific reference ranges for TSH should be applied. (B) Recommended reference range for TSH (I) 1st trimester : 0.1–2.5 mIU/L 2nd : 0.2–3.0 3rd : 0.3–3.5
  7. 7. Sample Trimester-Specific Reference Intervals for Serum TSH Trimester Reference First Second Third Haddow † 0.94 (0.08-2.73) 1.29 (0.39-2.70) Stricker ‡ 1.04 (0.09-2.83) 1.02 (0.20-2.79) 1.14 (0.31-2.90) Panesar † 0.8 (0.03-2.30) 1.1 (0.03-3.10) 1.3 (0.13-3.50) Soldin ‡ 0.98 (0.24-2.99) 1.09 (0.46-2.95) 1.2 (0.43-2.78) Bocos-Terraz ‡ 0.92 (0.03-2.65) 1.12 (0.12-2.64) 1.29 (0.23-3.56) Marwaha † 2.10 (0.60-5.00) 2.40 (0.43-5.78) 2.10 (0.74-5.70) (Thyroid 2011)†: 5th and 95th pefcentile, ‡: 2.5 th and 97.5th percentile
  8. 8. 제일병원 TSH 정상치 0.30 - 4.5 mU/L 임신 초기산모 TSH 정상 상한치를 4.5 에서 2.5 mU/L 로 변경 임신 초기산모 1,826명중, TSH > 2.5 인 경우가 387명 (21.0 %)
  9. 9. weeks number % percentile 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 Gestational week-specific TSH values (제일병원 2012)
  10. 10. Gestational weeksGestational weeks TSH Numbers (제일병원 산모인덱스 2010)
  11. 11. 0 50 100 150 6 7 8 9 10 11 12 13 14 0.0 1.0 2.0 3.0 4.0 5 6 7 8 9 10 11 12 13 TSH(mU/L) Gestational age (weeks) 95th 50th 5th Gestational age (weeks) Numbers Gestational age-specific reference ranges for TSH
  12. 12. Importance of Gestational Age–Specific Reference Ranges Singleton pregnancies (solid lines) and twin (dashed lines) (Dashe JS, Obstet Gynecol 2005)
  13. 13. Adverse maternal and fetal effects Associated with Overt hypothyroidism Overt hyperthyroidism Not associated with Subclinical hyperthyroidism ? Subclinical hypothyroidism (SCH)
  14. 14. Subclinical hypothyroidism (SCH) Many studies association between SCH and adverse pregnancy outcome (increased risk of placental abruption, preterm delivery, miscarriage & fetal death) Some studies no association
  15. 15. Children of treated women with hypothyroidism (N=14) Children of untreated women with hypothyroidism (N=48) Control (N=124) IQ score 111 100 107 p=0.20 p=0.005 IQ =< 85(%) 0 19 5 p=0.90 p=0.007 Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. (Haddow JE, N Engl J Med 1999) 62/25,000 children
  16. 16. Universal Screening vs Case Finding for Detection and Treatment of Thyroid Hormonal Dysfunction During pregnancy (Negro R, JCEM 2010) Women assessed 4657 95 excluded for known thyroid disease Randomized 4562 Case finding 2282 Universal screening 2280 Analyzed High risk 454 Euthyroid 432 Hypothyroid 20 Hyperthyroid 2 Low risk 1828 Euthyroid 1789 Hypothyroid 34 Hyperthyroid 5 Analyzed & check TSH High risk 481 Euthyroid 451 Hypothyroid 19 Hyperthyroid 2 Low risk 1789 Euthyroid 1747 Hypothyroid 44 Hyperthyroid 7 check TSH
  17. 17. Number of women experiencing at least one adverse outcome Case finding (n=2257) Universal screening (n=2259) High risk Low risk Total High risk Low risk Total Euthyroid without Ab 166 (41.3%) 659 (39.5%) 824 (39.9%) 179 (41.7%) 637 (39.1%) 816 (39.7%) Euthyroid with Ab 10 (40%) 49 (47.1%) 59 (45.7%) 13 (48.1%) 45 (42.9%) 58 (43.9%) Hypothyroid 9 (45%) 31 (91.2%) 40 (74.1%) 6 (31.6%) 15 (34.9%) 21 (33.9%) Hyperthyroid 2 (100%) 5 (100%) 7 (100%) 1 (50%) 4 (57.1%) 5 (55.5%) Total 187 (41.7%) 742 (41.1%) 930 (41.2%) 199 (41.7%) 701 (40.5%) 900 (39.8%) (Negro R, JCEM 2010)
  18. 18. Complications in patients with thyroid dysfunction, divided by study group (case finding or universal screening) and risk classification (high risk or low risk) (Negro R, JCEM 2010)
  19. 19. Antenatal Thyroid Screening and Childhood Cognitive Function (Lazarus JH, N Engl J Med 2012) 21,846 women 10,924 Screening (Assay within 1 wk) 10,922 Control (Assay after delivery) 499 (4.6%) tested positive 242 low fT4 232 high TSH 25 low fT4 & high TSH 499 LT4 at 13 gwk 390 children psychological test 404 children psychological test After delivery 551 (5.0%) tested positive 257 low fT4 264 high TSH 30 low fT4 & high TSH
  20. 20. (Lazarus JH, N Engl J Med 2012) Screening Gr (N=390) Control Gr (N=404) G wks median 12.3 12.3 NS interquartile range 11.6 – 13.6 11.6 – 13.5 NS TSH (median) median 3.8 3.2 NS interquartile range 1.5 – 4.7 1.2 – 4.2 NS IQ mean 99.2 ± 13.3 100.0 ± 13.3 0.40 <85 (% of children) 12.1 14.1 0.39
  21. 21. Cost-effective Universal screening is cost-effective, not only compared with no screening but also compared with screening of high-risk women. Universal screening remained cost-effective even when only overt hypothyroidism, rather than subclinical hypothyroidism, was detected and treated. (Dosiou C, J Clin Endocrinol Metab, 2012)
  22. 22. TSH screening in pregnant women ?
  23. 23. Endo Society (2012), committee did not reach consensus on the screening. “Some members recommended screening” “Some members recommended neither for nor against universal screening. These members strongly support aggressive case finding” TSH screening in pregnant women
  24. 24. The current recommendations for targeted screening for women at high risk for thyroid dysfunction Endocrine Society (2012) American Thyroid Association (2011) Aged > 30 years Aged > 30 FHx of autoimmune thyroid disease or Hypothyroidism FHx of thyroid disease Hx of thyroid surgery Hx of thyroid dysfunction and/or thyroid op Goiter Goiter Thyroid antibodies Thyroid antibodies Sx or signs of thyroid hypofunction Sx or signs suggestive of hypothyroidism T1DM or other autoimmune disorders T1DM or other autoimmune disorders Hx of miscarriage or preterm delivery Hx of miscarriage or preterm delivery Infertility Infertility Prior head or neck irradiation Prior head or neck irradiation Current levothyroxine replacement Living in a region with iodine deficiency Morbid obesity Treated with amiodarone or lithium Recent exposure to contrast agents
  25. 25. Screened thyroid function in 1560 pregnant women, 413 women (26.5%), as a high-risk group (PHx or FHx of thyroid disorder or PHx of other autoimmune disease) 12 of 40 women with raised TSH (30%) were in the low-risk group. (Vaidya B, J Clin Endocrinol Metab, 2005)
  26. 26. 55% of women with thyroid abnormalities would have been missed using a case-finding rather than a universal screening approach. (Horacek J, Eur J Endocrinol, 2010) Consensus guideline risk factor Occurrence (%) Personal history of a thyroid disorder 4 (8%) Family history of a thyroid disorder 15 (31%) Goitre 1 (2%) History of positive thyroid antibodies 0 (0%) Symptoms/signs of thyroid hypo/hyperfunction 0 (0%) History of type 1 diabetes mellitus 0 (0%) History of other autoimmune disorders 1 (2%) Infertility 0 (0%) History of head/neck irradiation 0 (0%) History of miscarriage or preterm delivery 7 (14%) None of them 27 (55%)
  27. 27. (in Cheil Hospital) 523 1st trimester women (mean age 33.6 ± 3.7 yrs, IUP 6.8 ± 2.0 wks) Age > 30 yrs 425 PHx of thyroid disease 46 FHx of thyroid disease 51 Age > 30 yrs or PHx or FHx 436 Low risk 87 women (16.6%) High risk 436 women (83.4%)
  28. 28. 2010년에 분만한 6072명에서 산모의 연령분포 (제일병원산모인덱스 2010) 평균연령 33.4 ± 3.6세 연령>30세 4782명 (78.6%)
  29. 29. (in Cheil Hospital) in 511 first trimester women, TPO-Ab (+) 65 / 511 (12.7%) TPO-Ab (+) with subclinical hypothyroidism 15 / 511 (2.9%) Hx of thyroid dysfunction or Tx (+) 7 / 15 (-) 8 / 15
  30. 30. Universal screening is superior in detecting thyroid dysfunction than selective screening. In Korea 1st visit : IUP 6.8 주 delivery age : 33.6 세
  31. 31. To screen or not to screen, that is the question.
  32. 32. - European Thyroid Association, 2010 42% responders screened all pregnant women for thyroid dysfunction. - American Thyroid Association, 2013 Universal screening was recommended by 74% of the survey respondents.

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