Transcript Hypothyroidism in pregnancy

HYPOTHYROIDISM
IN PREGNANCY
Mary Lacy
Case at the VA
 29yo G2P1 w/ h/o poorly controlled primary hypothyroidism. b-hcg
positive on 3/15 and TSH that same day of 101.5.
 Pt has been on 112mcg of levothyroxine since December when her
dose was increased from 88mcg 2/2 TSH of 40.
 What did we do?
 Increased dose to 150mcg based on 1.6mcg/kg and adding 30% for increased
demands in pregnancy
 Repeat labs (recommended q4-6 weeks in pregnancy rather than q6-8weeks)
 Most recent labs (at 11 weeks):
 TSH: 39.81
 Free T4: 1.31
Classifications of Hypothyroidism
 Overt Hypothyroidism: 0.3-0.5% of screened women
 Increased TSH, Decreased Free T4
 Subclinical Hypothyroidism: 2-2.5% of screened women
 Increased TSH, Normal Free T4
Changes in labs during pregnancy
 Increased TBG  Increased Total T4/Total T3
 secondary to increased Estrogen
 Serum TSH decreases early in gestation with rise in free T3/free T4
 Secondary to hCG stimulation of thyroid
 normalizes by end of first Trimester
 Normal TSH in pregnancy
 First trimester: 0.1-2.5 mIU/L
 Second Trimester: 0.2-3.0 mIU/L
 Third Trimester: 0.3-3.0 mIU/L
Thyroid in Fetal development
 Thyroid hormone receptor expressed in fetus at 8-10weeks
 Reports of when fetus begins to produce thyroid hormone vary, most
reports stated 18 weeks, some said 11-12 weeks
• Observational study between 1987 – 1999 in Argentina
• Followed 150 consecutive pregnancies of 114 women with primary
hypothyroidism (primarily chronic lymphocytic)
• 99 women were euthyroid on LT4
• 51 were hypothyroid – 16 with OH, 35 with SCH
TSH < 4
Thyroid Status at
Conception
Pregnancy Loss
Term Delivery
Euthryoid
(n = 99)
4/99 (4%)
84/99 (84.5%)
Hypothyroid
(n = 51)
16/51 (31.4%)
92.6%
0%
p<0.006
p<0.0001
p<0.006
30/51 (59%)
p = 0.18
66.7%
TSH > 4
20.8%
• 4,657 women screened with TSH/TPO-Ab within first 11 weeks of
gestation in Southern Italy
• Subset of women with TPO-Ab negativity:
• Group A: TSH < 2.5
• Group B: TSH between 2.5 – 5.0
• Study assessed pregnancy loss, pre-term and very pre-term delivery
p=0.006
• Retrospective analysis of TSH/freeT4/TPO-Ab in 2nd trimester serum samples of
25,216 pregnant women from 1987-1990 in Maine
• 47 women with TSH > 99.7% of all values
• 15 women with TSH in 98-99.7% + T4 < 7.75mcg/dL (4.6-12)
•Prospective study of 62 children born to mothers with hypothyroidism compared
to 124 control children from same schools
•7-9 year old children who were euthyroid at birth underwent 15 test of
intelligence, school performance, visual-motor performance, etc.
• RCT of 10 centers in UK and 1 in Italy
Target TSH 0.1-1.0
Contrasting these papers
Haddow 1999
Lazarus 2012
Type of study
Observational study of
RCT of treated vs
hypothyroid mothers (tx/no untreated “hypothyroidism”
tx) vs. non-hypothyroid
mothers
Serum Samples
2nd trimester
12-13 weeks
TSH Average
13.2
3.8/3.1
Child Testing
7-9 years
3 years
• Prospective study in the Netherlands between January - November 1994
• 448 pregnant women initially assessed
• Maternal fT4, TSH, TPO-Ab measured at 12 weeks gestation, 32 weeks
gestation, and post-partum
• 220 children from uncomplicated pregnancies/deliveries
• Neurodevelopment assessed at 10 months
Lowest 5% fT4
Lowest 10% fT4
Lowest 15% fT4
• Mean difference in Lowest 5% of
free T4 = 14.1* (5.9 – 22.3)
• Mean difference in lowest 10% =
7.4* (1.1 – 13.9)
• Difference of 10 points on PDI
score thought to reflect delay of
one month
R = 0.46; p=0.03
Lowest 20% fT4
• Observational case-control study in Maine in 2004 – 2006
• Free T4 measured in 5,734 women with normal TSH (0.1-3.5)
• Women with free T4 ≤ 3% matched with women in 10-90th %
• Measurement of Infant Development (VSID III) at age 2 years
So what should I do?
• If Hypothyroidism known prior to pregnancy – target TSH <2.5 (poor)
• Thyroxine requirements increase 30-50% by 4-6 weeks (good)
• can have patients increase dosing to 9 doses/week
• Targeted case finding for hypothyroidism as opposed to universal screening (fair)
• Treat overt hypothyroidism (good)
• Treat subclinical hypothyroidism
• improves obstetrical outcomes (fair)
• improves offspring development (poor)
• Patients with evidence of thyroid autoimmunity are at risk for OH, monitor them
throughout pregnancy (fair)