Hyperthyroidism in Pregnancy

Hyperthyroidism in pregnancy is overproduction of thyroid hormone (suppressed thyroid stimulating hormone with raised free thyroxine or triiodothyronine) complicating 0.1 to 0.4 percent of pregnancies.

• Graves disease is the cause in 85 percent (thyroid stimulating antibodies cross the placenta).
• Gestational transient thyrotoxicosis (1 to 3 percent): human chorionic gonadotrophin stimulates the thyroid in the first trimester, seen with hyperemesis, twins and molar pregnancy; resolves by 14 to 18 weeks.
• Others: toxic multinodular goitre, toxic adenoma, thyroiditis (subacute, postpartum), trophoblastic disease, iodine excess, amiodarone.
• Poorly controlled disease causes miscarriage, preterm birth, preeclampsia, fetal growth restriction, stillbirth, maternal heart failure and thyroid storm.

Weight loss or failure to gain, tachycardia (above 100 beats/min), palpitations, tremor, heat intolerance, sweating, anxiety, vomiting, diarrhoea, goitre, lid lag, exophthalmos and pretibial myxoedema (Graves), proximal weakness.

• Physiological pregnancy changes mimic mild hyperthyroidism.
• Differential diagnosis: normal pregnancy, hyperemesis gravidarum, gestational transient thyrotoxicosis, thyroiditis, anxiety, anaemia, phaeochromocytoma, arrhythmia, heart disease.
• Complications: maternal heart failure, atrial fibrillation, thyroid storm (precipitated by labour, infection, caesarean), miscarriage, preterm labour, preeclampsia, fetal and neonatal thyrotoxicosis (maternal receptor antibodies), fetal goitre, fetal hypothyroidism from over-treatment, low birth weight, stillbirth.

Thyroid stimulating hormone (suppressed; the lower limit of thyroid stimulating hormone is about 0.1 mIU/L in the first trimester, so values below 0.01 to 0.1 with raised free thyroxine indicate hyperthyroidism), free thyroxine and free triiodothyronine (use trimester-specific ranges), thyroid receptor antibodies (raised in Graves).

• Thyroid ultrasound; no radioiodine scan or uptake.
• Full blood count, liver profile (before antithyroid drugs), electrolytes, ECG.
• Fetal assessment: growth scans, fetal heart rate (above 170 beats/min), fetal goitre by ultrasound; antibody level at 20 to 24 weeks.

Supportive: rest, hydration, treatment of hyperemesis (ondansetron 4 mg, thiamine 100 mg), counselling about planned pregnancy.

Pharmacological

• Gestational transient thyrotoxicosis: supportive; antithyroid drugs are not needed unless severe (short course).
• Graves disease, first trimester: propylthiouracil 50 to 150 mg two to three times daily (up to 300 mg daily) until 16 weeks (carbimazole and methimazole cause embryopathy, mostly during weeks 6 to 10); from the second trimester, switch to carbimazole 5 to 15 mg daily (maximum 30 mg) or methimazole 5 to 15 mg daily because of the liver toxicity of propylthiouracil; use the lowest dose to keep free thyroxine in the upper part of the normal range.
• Block-and-replace regimens (antithyroid drug plus levothyroxine) are avoided because of fetal hypothyroidism.
• Symptom control: propranolol 10 to 40 mg two to three times daily for a short period (prolonged use risks fetal growth restriction and neonatal hypoglycaemia).
• Monitor free thyroxine and thyroid stimulating hormone every 2 to 4 weeks until stable then every 4 to 6 weeks; check full blood count and liver profile if fever, sore throat, jaundice or rash (agranulocytosis, hepatitis); stop the drug and avoid its use again.
• Thyroid storm: propylthiouracil 600 mg load then 200 to 300 mg every 6 hours, propranolol 1 to 2 mg IV (or 40 to 80 mg orally every 4 to 6 hours), hydrocortisone 100 mg IV every 8 hours, cooling, fluids, iodide (potassium iodide 5 drops every 6 hours) one hour after propylthiouracil, treat precipitant; intensive care.
• Fetal or neonatal thyrotoxicosis: maternal antithyroid drugs treat the fetus; consider levothyroxine only for fetal hypothyroid goitre.

Procedures: thyroidectomy in the second trimester for severe allergy to antithyroid drugs, non-adherence or uncontrolled disease; radioiodine is contraindicated in pregnancy and for 6 months before conception.

Special groups: women planning pregnancy (definitive treatment first, or switch to propylthiouracil), breastfeeding (carbimazole up to 20 mg daily or propylthiouracil up to 300 mg daily are acceptable, dosing after feeds), postpartum thyroiditis.

Red flags: fever, tachycardia above 140 beats/min, heart failure, agitation, jaundice or sore throat on drugs, fetal heart rate above 170 beats/min.

Follow-up: thyroid function every 2 to 4 weeks; antibody levels at 20 to 24 weeks (above 3 times normal means fetal risk); paediatric review and thyroid tests on cord blood or day 3 to 5 in the neonate; postpartum relapse is common, check at 6 weeks.