임신 중 갑상선 질환의 관리- 임창훈 교수

1. 임신 중 갑상선질환의 관리
관동의대 제일병원
내과 임창훈

2. 임신시 갑상선질환의 빈도
2010년 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 each
trimester?
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
Trimester
Reference First Second Third
Haddow 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)
Numbers
TSH
Gestational weeks Gestational weeks

10. (제일병원 산모인덱스 2010)
Numbers
TSH
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 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
Maternal hyperthyroidism
Maternal Fetal
Miscarriage LBW (Prematurity, Small-for-gestational age,
PIH IUGR)
Preterm delivery Goiter
CHF Hypothyroidism
Thyroid storm Stillbirth
Placenta abruptio Hyperthyroidism
Best Pract Res Clin Endocrinol Metab. 2004

15. 임신 중 약물의 태반 통과
(모체) (태반) (태아)
항갑상선제 갑상선기능저하증 유발
요오드 태아에 요오드 공급
갑상선 자극항체 갑상선기능항진증
갑상선호르몬 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 hypothyroidism
Number 14 48 124
IQ score 111 100 107
p-score 0.20 0.005

17. Should overt hypothyroidism be treated in
pregnancy?
Overt hypothyroidism (OH):
TSH > 2.5 mIU/L with fT4
or TSH ≥ 10 mIU/L
OH should be treated in pregnancy.

18. Subclinical hypothyroidism (SCH):
TSH 2.5~10 mIU/L with normal FT4
SCH 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 differ
from 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 with
Graves’ 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 be
differentiated from Graves’ hyperthyroidism
in 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
abortion
LT4 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 the
women 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 thyrotoxicosis
Thyroid 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 postpartum
thyroiditis (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 iodine
intake 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 infants
associated 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 출산한
후 시어머니가 끓여주는 미역국만 억지로 먹어
야 했다. 몽골에선 해산 후 양고기를 먹지만 한
국에선 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 the
following women (B)
Hx of thyroid dysfunction or surgery
Age >30 years
Sx of thyroid dysfunction or the presence of goiter
TPOAb positivity
T1DM or other autoimmune disorders
Hx of miscarriage or preterm delivery
Hx of head or neck radiation
FHx of thyroid dysfunction
Morbid obesity (BMI ≥ 40 kg/m2)
Use of amiodarone or iodinated radiologic contrast
Infertility
Residing in an area of iodine insufficiency

52. BUT
30% 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 / 10
Universal 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)