mandel presentation
TRANSCRIPT
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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
American Thyroid Association
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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
American Thyroid Association
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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