Endocrine disorders in pregnancy - thyroid disease
Description
Physiological changes - why the reference ranges move
- inc hCG -> weak TSH-receptor agonism (shared alpha subunit) -> TSH falls, fT4 rises in T1
- Peaks ~8-14 weeks, mirroring hCG
- inc oestrogen -> inc TBG -> inc total T4/T3 (use free hormones, or total T4 x 1.5)
- inc renal iodide clearance + fetal transfer -> inc iodine requirement ~50%
- Placental type 3 deiodinase inactivates T4/T3 -> inc maternal demand
- Thyroxine requirement rises 25-50% by ~week 8 in a treated hypothyroid woman
What crosses the placenta
| Crosses | Does not cross |
|---|---|
| TSH-receptor antibodies (TRAb), TPO and Tg antibodies | TSH |
| Thionamides (carbimazole, PTU) | hCG |
| TRH | Maternal thyroglobulin |
| Iodine and radioiodine | |
| Thyroxine - only in small amounts |
- *This table explains everything* - fetal Graves from maternal TRAb even after maternal thyroidectomy; fetal goitre from maternal thionamide; maternal T4 cannot rescue fetal hypothyroidism
- Fetal thyroid does not function until ~12 weeks - first-trimester neurodevelopment depends entirely on maternal T4
Epidemiology
- Overt hypothyroidism ~0.3-0.5%; subclinical 2-3%; isolated hypothyroxinaemia ~1-2%
- Thyroid autoantibodies in ~18% of pregnant women overall, and ~65% of those with a raised TSH
- Independent risk factor for infertility and sporadic miscarriage
- Thyrotoxicosis ~0.1-0.4%; hCG-mediated (gestational transient) far commoner than Graves
- Hyperemesis gravidarum - biochemical thyrotoxicosis in up to 60%
- Postpartum thyroiditis 5-10%; up to 25% in women with type 1 diabetes
- Australia: iodine-replete since mandatory bread fortification (2009), but pregnancy still requires supplementation
Aetiopathogenesis
Hypothyroidism
- Hashimoto (chronic autoimmune) thyroiditis - commonest in iodine-replete countries
- Prior thyroidectomy or radioiodine; iodine deficiency worldwide
- Central (pituitary), amiodarone, lithium, checkpoint inhibitors
Thyrotoxicosis
- hCG-mediated (gestational transient thyrotoxicosis)
- hCG cross-stimulates the TSH receptor. Very high hCG -> hydatidiform mole, choriocarcinoma, hyperemesis gravidarum, multiple pregnancy
- Suppressed TSH, normal-to-mildly raised fT4, TRAb negative, no goitre, no eye signs, resolves by ~18-20 weeks
- Graves disease - the commonest cause of true thyrotoxicosis in pregnancy
- Pregnancy is relatively immunosuppressive - Graves often improves in T2/T3 and rebounds postpartum**
- Toxic nodule, thyroiditis, struma ovarii
Postpartum thyroiditis
- Destructive autoimmune thyroiditis on immune reconstitution after delivery
- Hyperthyroid (1-6 months) -> hypothyroid (3-12 months) -> recovery; ~20-30% remain permanently hypothyroid
- TPO antibody positive; low radionuclide uptake (scan contraindicated if breastfeeding - use clinical course and TRAb)
Diagnosis
Reference ranges
- Use a trimester- and population-specific TSH range where the laboratory provides one
- Otherwise: T1 lower limit ~0.1 mU/L; upper limit ~4.0 mU/L (the old blanket 2.5 mU/L cutoff over-diagnosed and is no longer used)
- fT4 assays are unreliable in pregnancy (altered binding proteins) - interpret with TSH, not alone
Screening
- Targeted, not universal: prior thyroid disease or surgery/RAI, positive antibodies or goitre, T1DM or other autoimmunity, head/neck irradiation, age >30, BMI >=40, infertility or recurrent miscarriage, amiodarone/lithium/recent iodinated contrast, family history, prior preterm delivery, residence in an iodine-deficient area
Hypothyroidism
- Overt: inc TSH with dec fT4, or TSH >10
- Subclinical: inc TSH with normal fT4
- Confirm with a repeat TSH/fT4 at 4-6 weeks before treating a mildly raised TSH (<6 mU/L)
- Up to 80% of mild abnormalities normalise spontaneously - a brief delay causes no harm
Thyrotoxicosis - distinguishing the two causes
| Gestational transient | Graves | |
|---|---|---|
| TRAb | Negative | Positive |
| Goitre, bruit, orbitopathy | Absent | Present |
| Onset | T1, with hCG peak | Any; often pre-existing |
| Vomiting | Prominent | Not typical |
| Course | Resolves by 18-20 weeks | Persists |
- *Radionuclide uptake scanning is contraindicated in pregnancy* - the distinction is clinical + TRAb
- TRAb at 18-22 weeks in any woman with current or past Graves (including after thyroidectomy or radioiodine - the antibody persists)
- TRAb >3x upper limit -> fetal surveillance for goitre, tachycardia, growth restriction, hydrops
Management
Hypothyroidism
- Known hypothyroidism: increase levothyroxine by ~25-30% as soon as pregnancy is confirmed (a practical rule: two extra tablets per week), then titrate
- Target TSH in the lower half of the trimester-specific range (broadly <2.5 mU/L)
- Check TSH every 4 weeks until mid-gestation, then at least once around 30 weeks
- Return to the pre-pregnancy dose immediately postpartum and recheck at 6 weeks
- Separate levothyroxine from iron, calcium and multivitamins by 4 hours - a very common cause of apparent dose failure in pregnancy
Subclinical hypothyroidism - what changed in 2026
- *TPO antibody status is no longer used to decide whether to treat*
- This overturns the previous framework, which treated the TPOAb-positive woman at a lower TSH
- Decide on degree and persistence of TSH elevation, and gestation at detection
- TSH >6 mU/L -> reasonable to treat immediately
- TSH 4-6 mU/L -> repeat in 4-6 weeks and treat if persistent
- Treatment started after the first trimester has not been shown to improve obstetric or childhood neurocognitive outcomes - the window is early
- Euthyroid, TPOAb-positive women should NOT be offered levothyroxine for infertility, before fertility treatment, or for recurrent miscarriage
- Instead check thyroid function every 3-6 months preconception (7-9% develop hypothyroidism)
Thyrotoxicosis
- Gestational transient: supportive only - antiemetics, fluids, beta blocker briefly if needed. No thionamide
- Graves
- PTU in the first trimester - carbimazole/methimazole embryopathy (aplasia cutis, choanal and oesophageal atresia, omphalocele)
- Switch to carbimazole after the first trimester - PTU carries fulminant hepatotoxicity risk
- *Lowest possible dose, targeting maternal fT4 at or just above the upper limit of the non-pregnant range*
- Thionamides cross the placenta far more readily than T4 - normalising the mother makes the fetus hypothyroid and goitrous
- Block-and-replace is contraindicated in pregnancy for the same reason
- Radioiodine absolutely contraindicated; surgery only for uncontrolled disease, ideally in T2
- Beta blocker (propranolol, metoprolol) short-term; atenolol avoided - fetal growth restriction
- Thyroid storm: as outside pregnancy, plus obstetric input; a known precipitant of preterm labour
Postpartum thyroiditis
- Thyrotoxic phase: beta blocker only - no thionamide (nothing is being synthesised)
- Hypothyroid phase: levothyroxine, then attempt withdrawal after ~12 months (unless planning another pregnancy)
- Annual TSH thereafter - high rate of eventual permanent hypothyroidism
Iodine
- 150 microg/day supplement for all women planning pregnancy, pregnant or breastfeeding (NHMRC)
- Total requirement ~250 microg/day
- Avoid excess (>500 microg/day) and kelp - Wolff-Chaikoff -> fetal hypothyroidism and goitre
Nodules and cancer
- Ultrasound and FNA are safe in pregnancy
- Differentiated thyroid cancer: surgery can usually be deferred to postpartum unless rapid growth or nodal disease; radioiodine always deferred, and pregnancy avoided for 6 months after
Associations
- Untreated overt hypothyroidism -> miscarriage, pre-eclampsia, placental abruption, preterm birth, low birthweight, impaired neurocognitive development
- Thyroid autoimmunity -> infertility, miscarriage, postpartum thyroiditis
- Type 1 diabetes - postpartum thyroiditis in up to 25%
- Hyperemesis gravidarum, molar pregnancy, multiple gestation - hCG-mediated thyrotoxicosis
- Graves - fetal and neonatal thyrotoxicosis (transplacental TRAb), fetal goitre from thionamide
- Postpartum depression - check TSH, but the association is not causal in most
- Amiodarone, lithium, iodinated contrast, checkpoint inhibitors
Natural history & complications
- Gestational transient thyrotoxicosis resolves by 18-20 weeks; no fetal risk
- Graves usually improves through T2/T3 and rebounds in the first 3-6 months postpartum - anticipate it and warn her
- Neonatal Graves presents at 7-10 days as maternal thionamide clears; tachycardia, poor feeding, goitre, craniosynostosis. Self-limiting over 3-12 weeks as maternal antibody is cleared
- Postpartum thyroiditis: ~70-80% recover; 20-30% permanently hypothyroid, and it recurs in ~70% of subsequent pregnancies
- Adequately treated maternal hypothyroidism carries near-normal outcomes - the risk is undertreatment in the first trimester
- Congenital hypothyroidism is detected on newborn bloodspot screening; treat within 2 weeks to preserve IQ
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