Thyroid in pregnancy
Thyroid in pregnancy and the newborn
Pregnancy changes thyroid tests through three mechanisms: oestrogen raises binding globulin, hCG stimulates the TSH receptor, and iodine needs rise. The fetus relies on maternal thyroxine until its own gland works, and several maternal substances cross the placenta. CPSP tests the interpretation of tests in pregnancy, what crosses the placenta, and congenital hypothyroidism.
One of the most tested topics in past papers
Synthesis and transport
| Step | Detail | Blocked by |
|---|---|---|
| Trapping | Na+/I- symporter (NIS); also in salivary glands, stomach and lactating breast | Perchlorate, pertechnetate (trapped but not organified) |
| Oxidation, organification, coupling | Thyroid peroxidase (TPO) forms MIT and DIT on thyroglobulin; DIT + DIT gives T4, MIT + DIT gives T3 | Carbimazole (prodrug of methimazole), propylthiouracil |
| Storage | Iodinated thyroglobulin in colloid: weeks of supply | Explains the delay before antithyroid drugs work |
| Release | Endocytosis and proteolysis; iodine recycled by deiodination | Iodide excess (Wolff–Chaikoff effect) |
- The gland secretes about 90% T4; most T3 comes from peripheral deiodination. T3 binds the nuclear receptor more strongly. Half-life: T4 about 7 days, T3 about 1 day.
- Most T4 is carried on thyroxine-binding globulin (TBG), then transthyretin and albumin; only the tiny free fraction acts.
- A positive perchlorate discharge test indicates an organification defect.
- Thyroid hormone raises metabolic rate through Na+/K+-ATPase and oxygen use, induces LDL receptors and raises SHBG.
Maternal changes in pregnancy
| Change | Cause | Effect on tests |
|---|---|---|
| TBG rises (doubles by mid-pregnancy) | Oestrogen increases hepatic synthesis and slows clearance | Total T4 and T3 rise about 50%; free T4 normal; hypothyroid women need more levothyroxine from early pregnancy |
| hCG stimulates the TSH receptor | hCG, TSH, LH and FSH share an alpha subunit; specificity comes from the beta subunit; hCG peaks at 9–12 weeks | TSH falls in the first trimester; free T4 may rise slightly |
| Iodine need rises | Higher GFR increases renal iodide loss; iodide passes to the fetus | Intake about 250 micrograms/day (150 outside pregnancy); goitre in iodine-deficient valleys |
| Immune tolerance | Autoimmunity damps in late pregnancy, rebounds after delivery | Graves improves in the third trimester and flares postpartum |
- Gestational transient thyrotoxicosis: hyperemesis, suppressed TSH, mildly raised free T4, no goitre or eye signs, negative TSH receptor antibodies; settles by about 18 weeks as hCG falls. Very high hCG (molar pregnancy, twins) can cause frank thyrotoxicosis.
- Postpartum thyroiditis: best predicted by anti-TPO antibodies; the thyrotoxic phase shows low uptake on scan (destructive release), unlike Graves.
- Subclinical hypothyroidism: high TSH, normal free T4. With TPO antibodies early in pregnancy it is treated, because the early fetus depends on maternal T4.
- Graves disease: stimulating IgG to the TSH receptor (type II hypersensitivity). Hashimoto thyroiditis: mainly T-cell mediated (type IV), with Hürthle cells. Struma ovarii is an ovarian teratoma containing functioning thyroid tissue (low neck uptake).
Placenta and fetus
- Type 3 deiodinase in the placenta inactivates most maternal T4 and T3, yet enough T4 crosses to protect the fetal brain; in thyroid agenesis cord T4 is about one-third of normal, so the baby looks normal at birth.
- Fetal brain glia convert T4 to T3 with type 2 deiodinase.
- Fetal thyroid arises from pharyngeal floor endoderm (foramen caecum), traps iodide and makes T4 from 10–12 weeks; the fetal pituitary responds with TSH from about 18–20 weeks. Fetal T3 is low and reverse T3 high until birth.
| Crosses the placenta | Does not cross |
|---|---|
| TRH, iodide, antithyroid drugs, TSH receptor antibodies (IgG), some T4, radioiodine, amiodarone iodine | TSH |
- Consequences: radioiodine after 10–12 weeks ablates the fetal thyroid; amiodarone or excess antithyroid drug causes fetal goitre (neck extension, polyhydramnios, bradycardia); maternal TSH receptor antibodies (even after thyroidectomy) cause fetal and neonatal thyrotoxicosis.
- Drugs: propylthiouracil in the first trimester (carbimazole embryopathy: aplasia cutis, choanal and oesophageal atresia), then carbimazole because PTU causes severe hepatotoxicity. PTU also blocks peripheral T4 to T3 conversion. Both may cause agranulocytosis (sore throat, fever). Long-term beta-blockers impair fetal growth.
- Breastfeeding on carbimazole is safe at usual doses; radioiodine requires stopping breastfeeding because breast NIS concentrates iodide in milk.
Newborn
- TSH surge within minutes of birth (cooling) peaks at about 30 minutes, so very early heel-prick samples give false positives; screen on about day 3–5.
- Congenital hypothyroidism: commonest cause is thyroid dysgenesis (ectopic, often lingual, or absent gland); iodine deficiency is the commonest preventable cause worldwide. Signs develop over weeks: prolonged unconjugated jaundice (immature glucuronidation), large tongue, hoarse cry, umbilical hernia, wide posterior fontanelle, lethargy, constipation. Absent distal femoral epiphysis at term shows prenatal onset. Early treatment prevents intellectual disability.
- Neurological cretinism (deafness, spasticity, intellectual disability) follows maternal hypothyroxinaemia in severe iodine deficiency, even if the child is later euthyroid.
- Neonatal Graves appears around day 5–10 as the maternal antithyroid drug clears, and lasts until maternal antibodies clear. Blocking antibodies cause transient neonatal hypothyroidism.
- TSH-based screening misses central hypothyroidism (septo-optic dysplasia). Preterm babies often have low T4 with normal TSH from an immature axis.
- Thyroid hormone drives non-shivering thermogenesis in brown fat through uncoupling protein 1 (thermogenin).
Remember In pregnancy judge thyroid status by free T4 and trimester-specific TSH, never by total T4.
Exam trap TSH does not cross the placenta; TSH receptor antibodies, iodide and antithyroid drugs do.
Exam trap A suppressed TSH with hyperemesis at 10 weeks is usually hCG effect; check TSH receptor antibodies before calling it Graves.
Test yourself on this topic
5 of the 91 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
At booking, a 27-year-old woman has a TSH of 5.8 mU/L with a normal free T4. She has no symptoms. How are these results classified?
Answer: Subclinical hypothyroidism
A raised TSH with free T4 in the normal range is subclinical hypothyroidism: the pituitary senses a slight shortfall and increases TSH to keep T4 normal. In pregnancy it is judged against trimester-specific ranges, because the first-trimester upper limit is lower than outside pregnancy. Overt hypothyroidism needs a low free T4. Central hypothyroidism gives low T4 with low or normal TSH.
Classifying TFTs
- High TSH, normal T4: subclinical hypo
- High TSH, low T4: overt hypo
- Low TSH, low T4: central
- Use trimester-specific ranges
Remember TSH moves first; T4 follows later.
Exam trap Non-pregnant reference ranges may miss a raised TSH in the first trimester.
Why the other options are wrong
- Overt hypothyroidism Free T4 would be low.
- Central hypothyroidism TSH would be low or normal with low T4.
- Sick euthyroid syndrome Seen in severe illness, usually with low T3.
- Subclinical hyperthyroidism TSH would be low.
A newborn's screening scan shows a lingual thyroid. From which embryonic tissue does the thyroid gland arise?
Answer: Endoderm of the pharyngeal floor
The thyroid arises in week 4 as a midline thickening of the endoderm in the floor of the primitive pharynx, at the site later marked by the foramen caecum. It descends in front of the hyoid and larynx, attached by the thyroglossal duct, to reach the front of the trachea by week 7. Arrest of descent at the tongue base produces a lingual thyroid. Only the C cells come from elsewhere, via the ultimobranchial body.
Thyroid origin
- Pharyngeal floor endoderm
- Site: foramen caecum
- Descends via thyroglossal duct
- Arrest at tongue: lingual thyroid
Remember Thyroid starts at the tongue and walks down.
Exam trap The third pouch forms parathyroid and thymus, not thyroid follicles.
Why the other options are wrong
- Ectoderm of the stomodeum Forms Rathke's pouch and the anterior pituitary.
- Neural crest of the fourth arch Gives C cells via the ultimobranchial body, not follicles.
- Mesoderm of the second arch Forms muscles of facial expression.
- Endoderm of the third pouch Forms the inferior parathyroids and thymus.
A woman with Graves disease takes high-dose propylthiouracil throughout pregnancy. From about which gestation can the fetal pituitary respond to the drug-induced fall in fetal T4 by raising TSH and enlarging the fetal thyroid?
Answer: About 18–20 weeks
The fetal thyroid starts making T4 at about 10–12 weeks, but the hypothalamic–pituitary–thyroid feedback loop matures later. From around mid-gestation (18–20 weeks), fetal TSH rises when fetal T4 falls, so overtreatment with antithyroid drugs can then produce a fetal goitre. Before this, low T4 does not drive a strong TSH response. The axis keeps maturing until after birth.
Fetal thyroid axis
- T4 synthesis from 10–12 weeks
- Feedback matures by 18–20 weeks
- Fetal TSH rises if T4 falls
- Overtreatment then gives fetal goitre
Remember Gland first, feedback later.
Exam trap Do not confuse the start of fetal hormone synthesis with maturation of feedback.
Why the other options are wrong
- About 6–8 weeks The thyroid has not yet begun to make hormone.
- About 10–12 weeks The gland starts making T4 then, but feedback is still immature.
- About 34–36 weeks Feedback is established well before this.
- Only after birth Feedback works before birth, as fetal goitre shows.
A non-pregnant woman with untreated Graves disease has oligomenorrhoea. Her total testosterone and total oestradiol are raised, but free levels are normal. Which change explains these results?
Answer: Raised SHBG
Thyroid hormone stimulates hepatic production of sex hormone–binding globulin, so SHBG rises in hyperthyroidism and falls in hypothyroidism. More bound hormone raises total testosterone and oestradiol, while free levels stay close to normal. Altered sex steroid metabolism and gonadotrophin pulsatility contribute to the menstrual upset. Raised LH or prolactin would change free levels or cause other patterns.
Thyroid and SHBG
- Hyperthyroid: SHBG up
- Total testosterone and oestradiol up
- Free levels near normal
- Hypothyroid: SHBG down
Remember Thyroid excess raises SHBG.
Exam trap Raised prolactin goes with hypothyroidism through TRH, not with Graves disease.
Why the other options are wrong
- Raised TBG Carries thyroid hormone, not sex steroids; not raised by hyperthyroidism.
- Raised albumin Not changed this way.
- Raised LH Would raise free hormone production.
- Raised prolactin Seen in hypothyroidism, not hyperthyroidism.
Cord blood from a fetus at 30 weeks is analysed. Compared with an adult, which iodothyronine is present in relatively high concentration?
Answer: Reverse T3
In fetal life, type 3 deiodinase activity in the placenta and fetal tissues is high and type 1 activity in the liver is low. T4 is therefore converted mainly to inactive reverse T3, and fetal serum and amniotic fluid contain much reverse T3 with little T3. After birth, hepatic type 1 activity rises and T3 increases. This pattern lets tissues such as the brain make T3 locally only where it is needed.
Fetal iodothyronines
- High reverse T3
- Low T3 until birth
- High type 3 deiodinase
- T3 rises after birth
Remember Fetus: reverse T3 dominates.
Exam trap Free T4 is present in the fetus, but the characteristic excess is reverse T3.
Why the other options are wrong
- Free T3 Low in the fetus until late gestation and birth.
- Thyroxine-binding globulin A binding protein, not an iodothyronine.
- Calcitonin Not an iodothyronine.
- Thyroglobulin antibodies Antibodies, not hormone; absent in a normal fetus.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Endocrinology, Thyroid in pregnancy and the newborn
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