Thyroid in pregnancy

Dr Ash Gargya

Endocrinologist, RPA and Bankstown Hospitals

VMO, Norwest and Strathfield Private Hospitals

Maternal physiology and TSH recommendations

Changes in maternal thyroid physiology

• E2 ↑ TBG synthesis (2-fold) and sialylation → ↓ TBG plasma clearance → ↑ in total T4 (and T4 binding sites) and T3

• ↑ volume of distribution and placental T4 transfer (accounts for 35% cord T4)

• hCG has TSH-like activity → peak 10-12 wks → 1st trimester ↑ fT4 (i.e. thyroid hormone pool) and ↓ TSH (~20% pregnancies)

• ↑GFR → ↑ (2-fold) urinary iodine loss

0 10 20 30 40 Gestation (wks)

“Strains” the thyroid functional reserve esp if ATA +ve or iodine insufficient

What crosses the placenta?

T4 • TSH and T3 do not cross the placenta

IodineAnti-thyroid medications

• PTU and carbimazole

TSH receptor antibodies• A maternal level >3 times ULN in the

third trimester may increase the risk of neonatal Graves’

TSH reference ranges in pregnancy

Glinoer D. Nat Rev Endo 2010

9 studies between 2004-2009ATA –ve and iodine sufficientNon-pregnant TSH reference range (0.4-4.1)mIU/L

97.5th centile

2.5th centile

Mean

Current recommendations

Where available, use laboratory-specific and trimester-specific reference ranges in pregnancy

When not available, aim for:-

Pre-conception TSH 0.3-2.5mIU/L

1st trimester TSH 0.1-2.5mIU/L

2nd trimester TSH 0.3-3.0mIU/L

3rd trimester TSH 0.3-3.0mIU/L

ATA Guidelines July 2011

Current recommendations

fT4 less reliable in pregnancy• Depends on methodology (ED and MS gold

standard)• Effect of iodine insufficiency

When is fT4 measurement useful?• Differentiate OH from SH • Monitoring anti-thyroid therapy

o Aim fT4 upper non-pregnant RR (i.e. 15-20pmol/L)

• Central hypothyroidism

ALL pregnant and breastfeeding women should be on an iodine-containing (250mcg) supplement

Who should be screened pre-conception?

Universal screening is currently NOT advocated

Maternal hypothyroidism

What are the implications of maternal hypothyroidism?

OVERT hypothyroidism (OH)

• Definition: TSH >2.5 with low fT4

• TSH >10 regardless of fT4

• Obstetric: associated with miscarriage, SGA, prematurity, gestational hypertension and PPH

• Fetal: 7 point IQ deficit (age 7-9yo) with delays in language, attention and motor development [untreated maternal TSH>13] (Haddow 1999)

• T4 therapy IMPROVES outcomes (obstetric and fetal)

What are the implications of maternal hypothyroidism?

SUBCLINICAL hypothyroidism (SH)

• Affects 2-3% of all pregnancies

• Definition: TSH 2.5-10 with normal fT4

• Obstetric: associated with increase risk of miscarriage and pre-term delivery (OR 2-2.5 across multiple studies)

• Fetal: no convincing evidence that SH affects neuro-cognitive development

• SCARCE evidence confirming that T4 intervention improves outcomes (obstetric or fetal)

Adjusting and monitoring TFT on Thyroxine

For women with pre-existing hypothyroidism on Thyroxine

• Aim TSH 0.3-2.5 pre-conception

• Once pregnant, increase dose by 30% (usually = 2 extra tablets through the week)

• For athyreotic women a dose increase up to 50% is needed

• Monitor TFT 4-weekly till 20 weeks and once at 28-32 weeks

• Take prenatal/Ca/Fe supplements >3h gap from Thyroxine

• Post-delivery reduce to pre-pregnancy dose with 3-monthly monitring for 1 year• Hashimoto’s: dose may be 20% higher 1 year postpartum cf pre-

preg

What are the implications of positive thyroid autoimmunity?

Occurs in 5-15% of child-bearing women

Positive thyroid antibodies are associated with• SH and OH

• Postpartum thyroiditis (risk 30-50% if +ve in 1st trimester)

• Increased rate of miscarriage (OR 2.73)o ?Heightened immune dysregulation

o ?Thyroid hypofunction

o ?Increased maternal age

What are the implications of positive thyroid autoimmunity?

Guidelines recommend treating with T4 if• Euthyroid and history of recurrent miscarriage

• SH

If euthyroid with +ve ATA pre-conception

• 20% of these women will have a TSH>4 by the 3rd trimester

• Monitor 4-6 weekly till mid-gestation (and once at 28-32 weeks) for SH/OH

• Monitor TFT 3-monthly pp - increased risk of pp thyroiditis

ATA guidelines 2011

Maternal hyperthyroidism

What are the implications of maternal hyperthyroidism?

Affects 0.1-0.4% of pregnancies

85% have Graves’ disease

• Other causes include hCG-mediated thyrotoxicosis (hyperemesis gravidarum, twin pregnancy), toxic nodule/s, thyroiditis (subacute, postpartum – M/C or delivery <12 months), molar pregnancy

Overt hyperthyroidism associated with miscarriage, IUGR, pre-eclampsia, preterm delivery, thyroid storm, CCF

Subclinical hyperthyroidism is NOT associated with adverse feto-maternal outcomes

How to approach a low TSH in early pregnancy

Check fT4, TRAb

• If both elevated – treat with antithyroid meds

• fT3 may help confirm Graves’ - T3 toxicosis (DD AFTN)

• If normal fT4 and +ve TRAb – monitor TFT 4-weekly and treat once overtly hyperthyroid

• If normal fT4 and –ve TRAb, likely hCG-mediated thyrotoxicosis

Graves’ disease in pregnancy

Use lowest effective dose of ATD

PTU in the 1st trimester (monitor LFT) and carbimazole thereafter if continued therapy required

Maintain fT4 in the upper 1/3 of non-pregnant RR

Monitor TFT 4-weekly whilst on ATD

Check TRAb around 28-32 weeks – risk neonatal Graves’

1/3 women can stop ATD by 3rd trimester

High risk of relapse 4-8 months postpartum

Summary

Summary

Use laboratory-specific, trimester-specific RR in pregnancy

TSH 0.3-2.5 pre-conception and during the 1st trimester

TSH 0.3-3.0 during the 2nd and 3rd trimesters

If on Thyroxine, increase dose by 30-50% once pregnant with 4-weekly monitoring in the first half of pregnancy

ALL women should take an iodine–containing supplement

Maintain fT4 in upper 1/3 non-preg RR if on ATD