Thyroid Medicines During Pregnancy

Thyroid medicines in pregnancy keep maternal and foetal thyroid function normal while the foetus depends on maternal thyroxine until about 12 weeks and partially thereafter. Untreated hypothyroidism raises miscarriage, pre-eclampsia, preterm birth and lower infant IQ; uncontrolled thyrotoxicosis raises miscarriage, pre-eclampsia, heart failure, thyroid storm, growth restriction and foetal thyroid dysfunction.

Physiology. Human chorionic gonadotrophin lowers TSH in the first trimester; trimester-specific TSH ranges (when available) are about 0.1 to 2.5 mU/L in the first trimester, 0.2 to 3.0 in the second and 0.3 to 3.5 in the third. Without local ranges, use an upper limit of about 4.0 mU/L. Thyroxine requirement rises by 25 to 50% from 4 to 6 weeks.

Iodine. Iodine needs rise; a total intake of about 250 micrograms daily is advised in pregnancy and breastfeeding, and iodine deficiency remains relevant in parts of East Africa (goitre regions).

Established hypothyroidism. Levothyroxine, taken on an empty stomach 30 to 60 minutes before breakfast, or at bedtime 3 hours after the last meal. On a positive pregnancy test, raise the dose by 25 to 30% at once (for example 2 extra tablets each week, or 9 doses instead of 7). Check TSH 4 weeks later and adjust by 12.5 to 25 micrograms to a TSH under 2.5 mU/L.

New hypothyroidism in pregnancy. Levothyroxine 1.6 micrograms/kg orally once daily (full replacement), or 50 to 100 micrograms daily and titrate every 4 weeks. Overt hypothyroidism: start at the full dose.

Subclinical hypothyroidism. Treat if TSH is 4.0 mU/L or more, or if TSH is over 2.5 mU/L with positive thyroid peroxidase antibodies (approach varies; many treat TSH over 4.0 with any antibody status). Levothyroxine 25 to 50 micrograms daily, titrated every 4 weeks.

Hyperthyroidism and Graves disease.

• First trimester: propylthiouracil 50 to 150 mg orally 3 times daily (maximum 600 mg daily at the start, down to the lowest dose that keeps free T4 at or just over the upper limit of normal).
• From the second trimester: switch to carbimazole 5 to 15 mg once daily (propylthiouracil dose is roughly 10 to 15 times the carbimazole dose; methimazole about 60% of the carbimazole dose).
• Do not use block and replace; use the lowest antithyroid dose.
• Propranolol 10 to 40 mg orally 3 times daily for symptoms, short term only (growth restriction, neonatal hypoglycaemia).
• Thyroidectomy in the second trimester if drugs fail or are not tolerated; radioiodine is contraindicated.

Thyroid storm. Propylthiouracil 600 to 1000 mg orally or by nasogastric tube, then 200 to 250 mg every 4 hours; propranolol 60 to 80 mg every 4 hours (or esmolol infusion); hydrocortisone 100 mg IV every 8 hours; iodine solution one hour after the antithyroid dose (potassium iodide 5 drops of saturated solution every 6 hours, or as set by the local intensive care team); cooling, fluids and cause treatment.

Gestational transient thyrotoxicosis (hyperemesis). Supportive care only. Do not start antithyroid drugs unless features of Graves disease are present.

Postpartum. Return levothyroxine to the pre-pregnancy dose; check TSH at 6 weeks. Postpartum thyroiditis (3 to 6% of births) causes thyrotoxic then hypothyroid phases at 1 to 6 months, with beta-blocker for symptoms and levothyroxine if hypothyroid.

Antithyroid adverse effects. Agranulocytosis (about 0.3%, most often in the first 3 months; warn to stop the drug and have a full blood count for fever or sore throat), hepatotoxicity (propylthiouracil: severe and sometimes fatal, so limited to the first trimester), vasculitis, rash. Carbimazole and methimazole: aplasia cutis, choanal and oesophageal atresia, facial dysmorphism with first trimester exposure (highest weeks 6 to 10).

Levothyroxine interactions. Iron, calcium, aluminium antacids, sucralfate and some resins reduce absorption; separate by 4 hours. Proton pump inhibitors, enzyme inducers and soya also reduce effect.

Special groups.

• Graves disease: check thyroid-stimulating hormone receptor antibodies at 20 to 24 weeks; titres over 3 times the upper limit predict foetal and neonatal thyrotoxicosis.
• Kidney impairment: no thyroid-drug adjustment.
• Liver impairment: avoid propylthiouracil; monitor carbimazole.
• Breastfeeding: levothyroxine, propranolol, propylthiouracil up to 300 mg daily and carbimazole up to 20 mg daily (or methimazole 10 to 20 mg) are compatible with infant thyroid checks.
• Regional: goitre and iodine deficiency; do not give iodine supplements in Graves disease without specialist input.

Monitoring. TSH every 4 weeks to 20 weeks, then at least once at 26 to 32 weeks (hypothyroidism); TSH and free T4 every 2 to 4 weeks after any change. Antithyroid drugs: free T4 every 2 to 4 weeks, full blood count and liver tests at baseline and with symptoms. Foetal growth and heart rate from 28 weeks in Graves disease; neonatal thyroid function at day 3 to 5 after birth.

Stopping rules. Stop the antithyroid drug at once for neutropenia (neutrophils under 1.0 x 10^9/L), jaundice or transaminases over 3 times the upper limit. Reduce the dose as free T4 enters the normal range; many can stop by the third trimester if antibodies are low.

Referral and escalation. Refer overt thyroid disease, positive receptor antibodies, goitre with compression, thyroid nodules or storm to endocrinology and obstetric medicine; treat thyroid storm as a medical emergency in a high dependency unit.