Transcript THYROID DISEASE IN PREGNANCY: TREATING TWO PATIENTS

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 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
What if the mom’s thyroid doesn’t
work? ~2% of all pregnancies
Subclinical
Hypothyroidism
Overt
Spontaneous abortion5,7
10-70%
60%
1,2,4,6,9
Preeclampsia
“Maternal hypothyroidism is 0-17%
associated with 0-44%
2,3,4,6,7
increased
rate of pregnancy complications,
and
Abruption
0%
0-19%
the risk is greatest
in overt hypothyroidism
1,2,3,6
Stillbirth/fetal
loss
0-3%
0-12%
compared to subclinical hypothyroidism.”
LaFranchi, Thyroid 2005
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
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
And, we are still not getting it right . . .
Frequency (%)
Abnormal thyroid function tests in
pregnant hypothyroid women taking LT4
50
45
40
35
30
25
20
15
10
5
0
43
33
28
1st trimester
n=389
McClain, Am J Obstet Gynecol 2008
2nd trimester Both trimesters
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
2011 Guidelines:
Endocrine Society
American Thyroid Association
• All women attempting to conceive
and pregnant women take a
prenatal vitamin containing 150mcg
of potassium iodine
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. 14th
International Thyroid Congress, Sept 2010
Maternal Adverse Outcomes:
Negro 2010
PRIMARY ENDPOINT:
NO BENEFIT to pregnancy outcome
complications/patient
2
1.5
1
0.7
0.7
0.5
0
Universal Screen
Case Finding
Cognitive Development:
Cognitive development and Maternal Hypothyroidism
CATS 2010
PRIMARY ENDPOINT:
NO difference in IQ scores
120
IQ score
100
80
100
99
60
40
20
0
Universal Screen
Courtesy of John Lazarus ITC 2010
Control
• 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
What to do
2011 Guidelines:
Endocrine Society
American Thyroid Association
• Insufficient evidence to recommend
universal screening for thyroid disease in
pregnant women
• Aggressive detection of women at high risk
for thyroid dysfunction
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