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
0
10
20
30
40 Gestation (wks)
•
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
“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
Iodine
Anti-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
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
Current recommendations
 Where available, use laboratory-specific and trimesterspecific 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 iodinecontaining (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, preeclampsia, preterm delivery, thyroid storm, CCF
 Subclinical hyperthyroidism is NOT associated with adverse fetomaternal 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 4weekly 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