관동의대 제일병원

내과 임창훈

임신 중 갑상선질환의 관리

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%

(J Clin Endocrinol Metab 2007)

(Thyroid 2011)

(J Clin Endocrinol Metab 2012)

Normal TSH in pregnancy

The pattern of changes in thyroid function and hCG

Clinical Obstetrics and Gynecology 1997

0 10 20 30 40

Weeks of Gestation

TBG

hCG

total T4

free T4

TSH

Recommended reference range for TSH (I)

1st trimester : 0.1–2.5 mIU/L

2nd : 0.2–3.0

3rd : 0.3–3.0

What is the normal range for TSH in each

trimester?

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)

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 산모인덱스 2010)

Gestational weeks Gestational weeks

TS

H

Nu

mb

ers

(제일병원 산모인덱스 2010)

Gestational weeks Gestational weeks

TS

H

Nu

mb

ers

(제일병원 산모인덱스 2010)

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

(Haddow JE, 2004)

Gestational week-specific TSH values

(제일병원 산모인덱스 2010)

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

(Haddow JE, 2004)

Gestational week-specific TSH values

(제일병원 산모인덱스 2010)

Hypothyroidism in pregnancy

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

임신 중 약물의 태반 통과

(모체) (태아)

항갑상선제

요오드

갑상선 자극항체

갑상선호르몬

갑상선기능저하증 유발

태아에 요오드 공급

갑상선기능항진증

뇌조직 성장 (임신초기)

(태반)

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

treated women

with hypothyroidism

Children of

untreated women

with hypothyroidism

Control

Number 14 48 124

IQ score 111 100 107

p-score 0.20 0.005

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.

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)

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

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.

Hyperthyroidism in pregnancy

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.

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)

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

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)

Thyroid nodules in pregnancy

Age n Subjects with nodules (%)

30-39

40-49

50-59

60-69

117

960

200

23

36 (30.8)

355 (37.0)

83 (41.5)

15 (65.2)

Prevalence of thyroid nodule detected by US in the

women for health check-up (Yim, 2002)

FNA confers no additional risks to a pregnancy.

Thyroid nodules discovered during pregnancy that

have suspicious ultrasound features should be

considered for FNA. (I)

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)

(2007 Guideline)

When nodules are discovered to be malignant,

surgery should be offered in the 2nd trimester.

Postpartum thyroid dysfunction

Immunity in pregnancy

pregnant

Delivery

Postpartum (months)

activation

suppression

Graves’ disease Hashimoto’s thyroiditis

Imm

une a

ctivi

ty

Cellular immunity

Humoral immunity

3 6 9 12

Thyroid 1999;9:710

임상양상

Delivery

Thyro

id function

6 4 months 2

Persistent hypothyroidism

Transient hypothyroidism

Persistent thyrotoxicosis

Transient thyrotoxicosis

(Amino et al, 1999)

Delivery

Thyro

id function

6 4 months 2

(Transient hypothyroidism)

(Destructive thyrotoxicosis)

PPT

산후 갑상선기능장애 (Postpartum thyroid dysfunction) = Postpartum thyroiditis

Delivery

Thyro

id function

6 4 months 2

(Transient hypothyroidism)

(Destructive thyrotoxicosis)

Graves’ dis.

PPT

산후 갑상선기능장애 (Postpartum thyroid dysfunction) = Postpartum thyroiditis + Postpartum Graves’ disease

Thyr

oid

function

T3, T4 증가

TSH 감소

Thyr

oid

function

4 mo 2

Delivery, Abortion (?)

Thyr

oid

function

4 mo 2

Delivery, Abortion (?)

TSH R Ab (+)

TSH R Ab (-)

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)

(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)

Iodine and pregnancy

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)

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.

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

lactation

Frequency of

seaweed soup

intake (%)

Dietary iodine

intake (ug/day)

Iodine content

in human milk

(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

Subclinical hypothyroidism in Korean preterm infants

associated with high levels of iodine in breast milk J Clin Endocrinol Metab 2009

High Iodine Content of Korean Seaweed Soup:

A Health Risk for Lactating Women and Their Infants?

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).

Thyroid , 2011

Prevalence of Postpartum thyroid dysfunction

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

(Thyroid 1999)

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)

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)

Universal TSH screeening /

Case-finding approach

in pregnancy

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)

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

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)

(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)