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)