Post on 15-Dec-2015
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HYPOTHYROIDISM IN PREGNANCYMary 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
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%) 30/51 (59%)
p<0.0001 p = 0.18
TSH < 4
TSH > 4
92.6%
20.8%
p<0.006
0%
66.7%
p<0.006
• 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 hypothyroid mothers (tx/no tx) vs. non-hypothyroid mothers
RCT of treated vs untreated “hypothyroidism”
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
Lowest 20% fT4
R = 0.46; p=0.03
• 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
• 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)