THYROID DISEASE IN

PREGNANCY:
TREATING TWO
PATIENTS
Susan J. Mandel, MD MPH
Perelman School of Medicine,
University 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 hormonesmade 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 1
st
trimester
Fetus: Thyroid begins to function at 12
weeks gestation
And if the babys thyroid doesnt
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 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 1:50
pregnancies
Severe overt hypothyroidism 1:500
pregnancies
Subclinical Overt
Hypothyroidism
Spontaneous abortion
5,7
10-70% 60%
Preeclampsia
1,2,4,6,9
0-17% 0-44%
Abruption
2,3,4,6,7
0% 0-19%
Stillbirth/fetal loss
1,2,3,6
0-3% 0-12%
Anemia
2,3
0-2% 0-31%
Postpartum hemorrhage
2,3,4
0-17% 0-19%
Preterm birth
2,3,7,8
0-9% 20-31%
1
Montoro et al, Ann Intern Med 1981;
2
Davis et al, Obstet Gynecol 1988;
3
Leung et al,
Obstet Gynecol 1993;
4
Wasserstrum et al, Clin Endocrinol 1993;
5
Glinoer, Thyroid Today, 1995
6
Allan et al, J Med Screen 2002;
7
Abalovich et al, Thyroid 2002;
8
Stagnaro-Green et al, Thyroid, 2005;
9
Sahu et al,
Arch Gynecol Obstet 2009
Maternal hypothyroidism is associated with increased
rate of pregnancy complications, and the risk is
greatest in overt hypothyroidism compared to
subclinical hypothyroidism.
LaFranchi, Thyroid 2005
What if the moms thyroid doesnt 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 1
st
OB visit
TSH monitoring required during pregnancy
One 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 pregnant
hypothyroid women taking LT4
43
33
28
0
5
10
15
20
25
30
35
40
45
50
F
r
e
q
u
e
n
c
y

(
%
)
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 prenatal
vitamins labeled to contain iodine
Measured iodine content was only 75% of
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 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 HEALTH
Negro 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 HEALTH
Lazarus J et al. Controlled Antenatal Thyroid
Screening (CATS) Study. 14
th
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
c
o
m
p
l
i
c
a
t
i
o
n
s
/
p
a
t
i
e
n
t
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
I
Q

s
c
o
r
e
Universal Screen Control
What to do
However, secondary analyses for both studies
suggest a benefit
Negative results could be due to screening and
intervention at end of 1
st
trimesterTOO 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