Mandel Presentation

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THYROID DISEASE IN

PREGNANCY:TREATING TWO

PATIENTS

Susan J. Mandel, MD MPH

Perelman School of Medicine,

University of Pennsylvania


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Outline

Background Importance of thyroid hormone during

pregnancy

Hypothyroidism during pregnancy General population of women in the

child bearing years


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Thyroid gland

Thyroid hormonesmade from IODINE

Thyroxine (T4)

Triiodothyronine (T3) MOSTLY made in liver

Many targets in the human body

Synthetic T4 (LEVOTHYROXINE LT4)

readily available


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The importance of thyroid hormone for

normal growth and development


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Cretinism

Due to severe dietary iodine

deficiency

Severe hypothyroidism in BOTH

Mom and fetus

Impaired cognitive development

Poor growth

Iodine deficiency is considered

the most common cause of

preventable brain damage in theworld today (WHO 1994).

http://www.thyroidmanager.org/Chapter20/index.html


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Sources of thyroid hormone for the

fetus Mom: Thyroid hormone crosses the

placenta starting in 1sttrimester

Fetus: Thyroid begins to function at 12weeks gestation


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What if the moms thyroid doesnt work?

Hypothyroidism

Hashimotos thyroiditis

Prior ablation with radioactive iodine

Prior thyroid surgery

Detected by a blood test (TSH)

Spectrum

Mild subclinical hypothyroidism 1:50pregnancies

Severe overt hypothyroidism 1:500

pregnancies


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Subclinical Overt Hypothyroidism

Spontaneous abortion5,7 10-70% 60%

Preeclampsia1,2,4,6,9 0-17% 0-44%

Abruption2,3,4,6,7 0% 0-19%

Stillbirth/fetal loss1,2,3,6 0-3% 0-12%

Anemia2,3 0-2% 0-31%

Postpartum hemorrhage2,3,4 0-17% 0-19%Preterm birth2,3,7,8 0-9% 20-31%

1Montoro et al, Ann Intern Med 1981; 2Davis et al, Obstet Gynecol 1988; 3Leung et al,

Obstet Gynecol 1993; 4Wasserstrum et al, Clin Endocrinol 1993; 5Glinoer, Thyroid Today, 1995

6Allan et al, J Med Screen 2002; 7Abalovich et al, Thyroid 2002; 8Stagnaro-Green et al, Thyroid, 2005; 9Sahu et al,Arch Gynecol Obstet 2009

Maternal hypothyroidism is associated with increased

rate of pregnancy complications, and the risk isgreatest in overt hypothyroidism compared to

subclinical hypothyroidism.LaFranchi, Thyroid 2005

What if the moms thyroid doesnt work?

~2% of all pregnancies


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For hypothyroid women taking levothyroxine

(LT4) who become pregnant

Increased LT4 dosage required in majority of

woman

Average dose increase about 30% TIMING for increase as early at 7-8 weeks

gestation USUALLY prior to 1st OB visit

TSH monitoring required during pregnancy

One option: take two additional LT4 pills/week

Yassa J Clin Endocrinol Metab 2010 95:3234


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And, we are still not getting it right . . .

Abnormal thyroid function tests in pregnant

hypothyroid women taking LT4

43

33

28

0

5

10

15

20

25

3035

40

45

50

Frequency(%

)

1st trimester 2nd trimester Both trimesters

McClain, Am J Obstet Gynecol 2008

n=389


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2011 Guidelines:

Endocrine Society

American Thyroid Association

Pre conception education of hypothyroid

women and optimization of LT4 dosage Check thyroid function tests as soon as

pregnancy confirmed and consider empirically

increasing LT4 dose by taking 2 additionalLT4 tablets per week


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Thyroid health in pregnant women

without thyroid disease

Daily iodine requirements increase inpregnancy WHO 250mcg/day

Institute of Medicine 220mcg/day

NOT all prenatal vitamins contain iodine!

In the USA, as of 2009, only 51% of prenatalvitamins labeled to contain iodine

Measured iodine content was only 75% oflabeled content!

Leung A et al N Engl J Med 2009 360:9


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All women attempting to conceive and

pregnant women take a prenatal vitamincontaining 150mcg of potassium iodine

2011 Guidelines:

Endocrine Society



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Screening

Prevalent disease

Screening test for disease identification

Adverse outcome related to disease Therapy that ameliorates outcome


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Recent Developments for

Subclinical Hypothyroidism

2 prospective randomized controlled trials

MATERNAL HEALTH

Negro R et al, Universal Screening vs Case

Finding for Detection and Treatment of ThyroidDysfunction During Pregnancy, J Clin

Endocrinol Metabolism 2010 95:1699

FETAL HEALTH

Lazarus J et al. Controlled Antenatal Thyroid

Screening (CATS) Study. 14thInternational

Thyroid Congress, Sept 2010

M t l Ad O t


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Maternal Adverse Outcomes:Negro 2010

PRIMARY ENDPOINT:NO BENEFIT to pregnancy outcome

0.7 0.7

0

0.5

1

1.5

2

compli

cations/patient

Universal Screen Case Finding

Cognitive Development:


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Cognitive development and Maternal Hypothyroidism

Courtesy of John Lazarus ITC 2010

Cognitive Development:CATS 2010

PRIMARY ENDPOINT:NO difference in IQ scores

100 99

0

20

40

60

80

100

120

IQ

score

Universal Screen Control


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What to do

However, secondary analyses for both studies

suggest a benefit

Negative results could be due to screening andintervention at end of 1sttrimesterTOO LATE


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Insufficient evidence to recommend universal

screening for thyroid disease in pregnantwomen

Aggressive detection of women at high risk for

thyroid dysfunction

2011 Guidelines:

Endocrine Society



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Women at risk for hypothyroidism

History of thyroid dysfunction or prior thyroid

surgery

Signs or symptoms of thyroid problem

Women older than age 30

Presence of other autoimmune disorders

Type 1 diabetes, rheumatoid arthritis

Family history of thyroid dysfunction History of miscarriage or preterm labor


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What is needed . . .

Education programs targeted to patients and care

providers HYPOTHYROID PREGNANT patients: HIGHER

thyroid hormone doses

All women: IODINE containing prenatal vitamins

Partnerships with public health, government andprofessional organizations to insure all prenatalvitamins contain 150mcg of potassium iodine

Exploration of the feasibility of a randomizedcontrolled trial that screens, identifies, and treatsthyroid dysfunction in women PRIOR to conception


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Thank you for your attention

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