1. Thyroid in pregnancy Dr Ash Gargya
Endocrinologist, RPA and Bankstown Hospitals
VMO, Norwest and Strathfield Private Hospitals

2. Maternal physiology and TSH recommendations

3. 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 wks → 1st trimester ↑ fT4 (i.e. thyroid hormone pool) and ↓ TSH (~20% pregnancies)
↑GFR → ↑ (2-fold) urinary iodine loss
Gestation (wks)
“Strains” the thyroid functional reserve esp if ATA +ve or iodine insufficient

4. What crosses the placenta?
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’

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

6. Current recommendations
Where available, use laboratory-specific and trimester- specific reference ranges in pregnancy
When not available, aim for:-
Pre-conception TSH mIU/L
1st trimester TSH mIU/L
2nd trimester TSH mIU/L
3rd trimester TSH mIU/L
ATA Guidelines July 2011

7. 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 pmol/L)
Central hypothyroidism
ALL pregnant and breastfeeding women should be on an iodine- containing (250mcg) supplement

8. Who should be screened pre-conception?

9. Universal screening is currently NOT advocated

10. Maternal hypothyroidism

11. 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)

12. What are the implications of maternal hypothyroidism?
SUBCLINICAL hypothyroidism (SH)
Affects 2-3% of all pregnancies
Definition: TSH with normal fT4
Obstetric: associated with increase risk of miscarriage and pre-term delivery (OR across multiple studies)
Fetal: no convincing evidence that SH affects neuro-cognitive development
SCARCE evidence confirming that T4 intervention improves outcomes (obstetric or fetal)

13. Adjusting and monitoring TFT on Thyroxine
For women with pre-existing hypothyroidism on Thyroxine
Aim TSH 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 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

14. 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

15. 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 weeks) for SH/OH
Monitor TFT 3-monthly pp - increased risk of pp thyroiditis

16. ATA guidelines 2011

17. Maternal hyperthyroidism

18. What are the implications of maternal hyperthyroidism?
Affects % 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

19. 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

20. 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 weeks – risk neonatal Graves’
1/3 women can stop ATD by 3rd trimester
High risk of relapse 4-8 months postpartum

21. Summary

22. Summary Use laboratory-specific, trimester-specific RR in pregnancy
TSH pre-conception and during the 1st trimester
TSH 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