THYROID DISEASE THYROID DISEASE IN IN

PREGNANCY:PREGNANCY:TREATING TWO TREATING TWO

PATIENTSPATIENTS

Susan J. Mandel, MD MPHSusan J. Mandel, MD MPH

Perelman School of Medicine, Perelman School of Medicine,

University of PennsylvaniaUniversity of Pennsylvania

Outline

• Background• Importance of thyroid hormone

during pregnancy• Hypothyroidism during pregnancy• General population of women in

the child bearing years

Thyroid gland

• Thyroid hormones—made from IODINE– Thyroxine (T4)– Triiodothyronine (T3) MOSTLY made in liver

• Many targets in the human body• Synthetic T4 (LEVOTHYROXINE LT4)

readily available

The importance of thyroid hormone for normal growth and development

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 the world today (WHO 1994).

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

Sources of thyroid hormone for the fetus

• Mom: Thyroid hormone crosses the placenta starting in 1st trimester

• Fetus: Thyroid begins to function at 12 weeks gestation

And if the baby’s thyroid doesn’t work. . . .

• Congenital hypothyroidism affects 1:3000 live births in the US

• Newborn screening programs in all 50 states

• Detection and treatment by 1 month of life results in normal outcomes

• THEREFORE, maternal thyroid hormone can protect fetal development in utero

What if the mom’s thyroid doesn’t work?

• “Hypothyroidism” – Hashimoto’s thyroiditis– Prior ablation with radioactive iodine– Prior thyroid surgery

• Detected by a blood test (TSH)• Spectrum

– Mild “subclinical” hypothyroidism 1:50 pregnancies

– Severe “overt” hypothyroidism 1:500 pregnancies

Subclinical OvertHypothyroidism

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, 19956Allan 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 Maternal hypothyroidism is associated with increased rate of pregnancy complications, and increased rate of pregnancy complications, and the risk is greatest in overt hypothyroidism the risk is greatest in overt hypothyroidism compared to subclinical hypothyroidism.”compared to subclinical hypothyroidism.”

LaFranchi, Thyroid 2005

What if the mom’s thyroid doesn’t work? ~2% of all pregnancies

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

pregnancyOne option: take two additional LT4 pills/weekOne option: take two additional LT4 pills/week

Yassa J Clin Endocrinol Metab 2010 95:3234

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

Abnormal thyroid function tests in Abnormal thyroid function tests in pregnant hypothyroid women taking LT4pregnant hypothyroid women taking LT4

43

3328

05

101520253035404550

Frequency

(%

)

1st trimester 2nd trimester Both trimesters

McClain, Am J Obstet Gynecol 2008

n=389

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 additional LT4 tablets per week

Thyroid health in pregnant women without thyroid disease

• Daily iodine requirements increase in pregnancy – WHO 250mcg/day– Institute of Medicine 220mcg/day

• NOT all prenatal vitamins contain iodine!• In the USA, as of 2009, only 51% of In the USA, as of 2009, only 51% of

prenatal vitamins labeled to contain prenatal vitamins labeled to contain iodineiodine

• Measured iodine content was only 75% of Measured iodine content was only 75% of labeled content!labeled content!

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

• All women attempting to conceive and pregnant women take a prenatal vitamin containing 150mcg of potassium iodine

2011 Guidelines: Endocrine Society

American Thyroid Association

Screening• Prevalent disease• Screening test for disease identification• Adverse outcome related to disease• Therapy that ameliorates outcome

Screening: Thyroid disease in pregnancy

• Prevalent disease– YES--~2% of all pregnanciesYES--~2% of all pregnancies

• Screening test for disease identification– YES

• Adverse outcome related to disease– YES

• Therapy that ameliorates outcome– Therapy —YES– Outcome improved — so far NO

Recent Developments for Subclinical Hypothyroidism

2 prospective randomized controlled trials

MATERNAL HEALTHNegro R et al, Universal Screening vs Case Finding for Detection and Treatment of Thyroid Dysfunction During Pregnancy, J Clin Endocrinol Metabolism 2010 95:1699

FETAL HEALTHLazarus J et al. Controlled Antenatal Thyroid Screening (CATS) Study. 14th International Thyroid Congress, Sept 2010

Maternal Adverse Outcomes: Negro 2010

PRIMARY ENDPOINT:NO BENEFIT to pregnancy outcome

0.7 0.7

0

0.5

1

1.5

2

com

plica

tions/p

ati

ent

Universal Screen Case Finding

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 s

core

Universal Screen Control

What to doWhat to do

• However, secondary analyses for both studies suggest a benefit

• Negative results could be due to screening and intervention at end of 1st trimester—TOO LATE

• Insufficient evidence to recommend universal screening for thyroid disease in pregnant women

• Aggressive detection of women at high risk for thyroid dysfunction

2011 Guidelines: Endocrine Society

American Thyroid Association

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

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 and professional organizations to insure all prenatal vitamins contain 150mcg of potassium iodine

• Exploration of the feasibility of a randomized controlled trial that screens, identifies, and treats thyroid dysfunction in women PRIOR to conception

Thank you for your attention