Chang Hoon Yim

 

Kwandong University

Cheil General Hospital

Endocrine Controversy in Pregnancy: Thyroid screening in pregnant women

Maternal hypothyroidismMaternal 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

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?

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

산모 과거력상 갑상선질환의 빈도 비교

2009 년 6353 명에서 314 명 (4.9%)2010 년 7010 명에서 326 명 (4.7%) ( 제일병원산모인덱스 2009, 2010)

2009 년 2010 년

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%

314 명 4.9% 326 명 4.7%

Serum TSH testing is inexpensive, is widely avail-able, 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

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

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 1,826 명중 ,

TSH > 2.5 인 경우가 387 명 (21.0 %)

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)

Gestational weeksGestational weeks

TS

H

Num

bers

( 제일병원 산모인덱스 2010)

6 7 8 9 10 11 12 13 140

50

100

150

5 6 7 8 9 10 11 12 130.0

1.0

2.0

3.0

4.0

Gestational age (weeks)

TS

H (

mU

/L)

95th

50th

5th

Gestational age (weeks)

Num

ber

sGestational age-specific reference ranges for TSH

Importance of Gestational Age–Specific Reference Ranges Singleton pregnancies (solid lines) and twin (dashed lines)

(Dashe JS, Obstet Gynecol 2005)

Adverse maternal and fetal effects

Associated with

Overt hypothyroidism

Overt hyperthyroidism

Not associated with

Subclinical hyperthyroidism

? Subclinical hypothyroidism (SCH)

Subclinical hypothyroidism (SCH)

Many studies

association between SCH and adverse preg-nancy outcome (increased risk of placental abruption, preterm delivery, miscarriage & fetal death)

Some studies

no association

Children of treated women

with hypothyroidism(N=14)

Children of untreated women with hypothy-

roidism(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

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

Randomized4562

Case finding2282

Universal screening

2280

Analyzed

High risk454

Euthyroid432

Hypothy-roid20

Hyperthy-roid

2

Low risk1828

Euthyroid1789

Hypothy-roid34

Hyperthy-roid

5

Analyzed & check TSH

High risk481

Euthyroid451

Hypothy-roid19

Hyperthy-roid

2

Low risk1789

Euthyroid1747

Hypothy-roid44

Hyperthy-roid

7

check TSH

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)

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)

Antenatal Thyroid Screening and ChildhoodCognitive Function (Lazarus JH, N Engl J Med 2012)

21,846 women

10,924 Screening(Assay within 1

wk)

10,922 Control(Assay after deliv-

ery)499 (4.6%) tested posi-

tive242 low fT4

232 high TSH25 low fT4 & high TSH

499 LT4 at 13 gwk

390 childrenpsychological

test

404 childrenpsychological

test

After delivery

551 (5.0%) tested posi-tive

257 low fT4264 high TSH

30 low fT4 & high TSH

(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

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)

TSH screening in pregnant women ?

Endo Society (2012), committee did not reach consensus on the screening.

“Some members recommended screening”

“Some members recommended neither for nor against uni-versal screening. These members strongly support ag-gressive case finding”

TSH screening in pregnant women

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 orHypothyroidism

FHx of thyroid disease

Hx of thyroid surgery Hx of thyroid dysfunction and/or thyroid opGoiter GoiterThyroid antibodies Thyroid antibodiesSx or signs of thyroid hypofunction Sx or signs suggestive of hypothyroidismT1DM or other autoimmune disorders T1DM or other autoimmune disordersHx of miscarriage or preterm delivery Hx of miscarriage or preterm deliveryInfertility InfertilityPrior head or neck irradiation Prior head or neck irradiationCurrent levothyroxine replacement  Living in a region with iodine deficiency  

  Morbid obesity

  Treated with amiodarone or lithium

  Recent exposure to contrast agents

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)

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%)

(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%)

2010 년에 분만한 6072 명에서 산모의 연령분포 ( 제일병원산모인덱스 2010)

평균연령 33.4 ± 3.6 세

연령 >30 세4782 명 (78.6%)

(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

Universal screening is superior in detecting thyroid dysfunction than selective screening.

In Korea

1st visit : IUP 6.8 주 delivery age : 33.6 세

To screen or not to screen,

that is the question.

- 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.