임창훈(단국대 제일병원)

1. Chang Hoon Yim
Dankook University
Cheil General Hospital
Thyroid disease in Pregnancy

3. 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
PIH
Preterm delivery Goiter
CHF Hypothyroidism
Thyroid storm Stillbirth
Placenta abruptio Hyperthyroidism
Maternal hyperthyroidism

4. 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?

5. Prevalence of thyroid dysfunction
in pregnant women
0.3 – 0.5% Overt hypothyroidism
2 – 2.5% Subclinical hypothyroidism (SCH)
Subclinical hyperthyroidism
0.1 – 0.4% Overt Hyperthyroidism

6. 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%

7. 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 (3.0)

8. 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

9. 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 %)

10. 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)

11. Gestational weeksGestational weeks
TSH
Numbers
(제일병원 산모인덱스 2010)

12. 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

13. Importance of Gestational Age–Specific Reference Ranges
Singleton pregnancies (solid lines) and twin (dashed lines)
(Dashe JS, Obstet Gynecol 2005)

14. (Zornitzki T, IMAJ 2014)

15. What is the Upper Limit of Serum TSH During the First
Trimester in Chinese Pregnant Women?
(Chenyan Li, J Clin Endocrinol Metab , 2014)
The median of TSH from 4 to 6 weeks was significantly higher than
from 7 to 12 weeks (2.15 [0.56 –5.31] mIU/L vs 1.47 [0.10–4.34]
mIU/L, p= .001).
The upper limit of serum TSH in the first trimester was much higher
than 2.5 mIU/L in Chinese pregnant women.
Thyroid Function in Pregnancy: What Is Normal?
(Marco Medici, Clinical Chemistry, 2015)
Institutions do not rely on fixed universal cutoff concentrations, but
calculate their own pregnancy-specific reference intervals.

16. Adverse maternal and fetal effects
Associated with
Overt hypothyroidism
Overt hyperthyroidism
Not associated with
Subclinical hyperthyroidism
? Subclinical hypothyroidism (SCH)

17. 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

18. 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

19. 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

20. 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)

21. 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)

22. 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

23. (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

24. 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)

25. TSH screening in pregnant women ?

26. 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

27. 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

28. 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)

29. 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%)

30. (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

31. (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%)

32. 2010년에 분만한 6072명에서 산모의 연령분포
(제일병원산모인덱스 2010)
평균연령
33.4 ± 3.6세
연령>30세
4782명 (78.6%)

33. Universal screening is superior in detecting
thyroid dysfunction than selective screening.
In Korea
1st visit : IUP 6.8 주
delivery age : 33.6 세

34. To screen or not to screen,
that is the question.

35. - 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.

36. Screening Pregnant Women for Overt Thyroid Disease
(Alex Stagnaro-Green, JAMA, 2015)
Sufficient evidence exists for the routine screening to
detect and treat overt thyroid disease during pregnancy.
The lack of data regarding the treatment of subclinical
hypothyroidism should not affect the decision to screen for
overt thyroid disease.