Thyroid in pregnancy

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Thyroid in pregnancy

• Dr Ash Gargya
• Endocrinologist, RPA and Bankstown Hospitals
• VMO, Norwest and Strathfield Private Hospitals

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Maternal physiology and TSH recommendations
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Changes in maternal thyroid physiology
Concentration of hormone

• 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
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What crosses the placenta?

• T4
• TSH and T3 do not cross the placenta
• Iodine
• Anti-thyroid medications
• PTU and carbimazole
• TSH receptor antibodies
• A maternal level gt3 times ULN in the third
  trimester may increase the risk of neonatal
  Graves

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TSH reference ranges in pregnancy
97.5th centile
Mean
2.5th centile
9 studies between 2004-2009 ATA ve and iodine
sufficient Non-pregnant TSH reference range
(0.4-4.1)mIU/L
Glinoer D. Nat Rev Endo 2010
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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
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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
• 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

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Who should be screened pre-conception?
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Universal screening is currently NOT advocated
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Maternal hypothyroidism
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What are the implications of maternal
hypothyroidism?

• OVERT hypothyroidism (OH)
• Definition TSH gt2.5 with low fT4
• TSH gt10 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 TSHgt13 (Haddow 1999)
• T4 therapy IMPROVES outcomes (obstetric and fetal)

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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)

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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 gt3h gap from
  Thyroxine
• Post-delivery reduce to pre-pregnancy dose with
  3-monthly monitring for 1 year
• Hashimotos dose may be 20 higher 1 year
  postpartum cf pre-preg

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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)
• ?Heightened immune dysregulation
• ?Thyroid hypofunction
• ?Increased maternal age

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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 TSHgt4 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

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ATA guidelines 2011
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Maternal hyperthyroidism
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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 lt12 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

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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

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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

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Summary
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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 iodinecontaining
  supplement
• Maintain fT4 in upper 1/3 non-preg RR if on ATD