Thyroid Hormone Preparations

Thyroid hormone preparations replace or supplement endogenous thyroid hormone. Levothyroxine (T4) is the usual replacement; liothyronine (T3) is used for rapid effect in myxoedema coma and in selected cases. Desiccated animal thyroid extract is not advised.

Mechanism. Levothyroxine is a prohormone converted by deiodinases to triiodothyronine, which binds nuclear thyroid receptors and regulates gene transcription, raising metabolic rate and affecting heart rate, growth, neurological development and lipid metabolism.

Pharmacokinetics. Levothyroxine oral absorption is 60 to 80%, needs gastric acid and a fasting state, and half-life is about 7 days, so steady state takes 6 to 8 weeks. Liothyronine absorption is about 95% and half-life about 1 day, giving peaks and troughs.

Levothyroxine. Tablets 25, 50, 75, 100, 125 and 150 micrograms and liquid forms. Switching between products is done with a TSH check at 6 to 8 weeks.

Liothyronine. Tablets 5, 10 and 20 micrograms, intravenous form for myxoedema coma. Not used for routine replacement.

Combination T4 with T3. Not advised routinely; considered only by a specialist for persistent symptoms with a normal TSH.

• Hypothyroidism, adult: full replacement is about 1.6 micrograms/kg daily. Healthy adults under 50 may start at the full dose; those over 50 or with coronary disease start at 25 to 50 micrograms daily (12.5 to 25 micrograms with unstable angina or recent myocardial infarction), increasing by 25 micrograms every 6 to 8 weeks.
• Administration: a single dose with water, 30 to 60 minutes before breakfast, or at bedtime at least 3 hours after the last meal. Separate by 4 hours from calcium, iron, antacids, sucralfate, bile acid resins and aluminium.
• Target: TSH within the laboratory reference range (about 0.4 to 4.0 mU/L), rechecked 6 to 8 weeks after any dose change, then annually.
• Myxoedema coma: levothyroxine 200 to 400 micrograms intravenously as a loading dose (lower in older adults and cardiac disease), then 1.6 micrograms/kg daily at 75% of the oral dose intravenously. Give hydrocortisone 100 mg intravenously every 8 hours before or with it. Add liothyronine 5 to 20 micrograms intravenously then 2.5 to 10 micrograms every 8 hours in selected cases.
• Thyroid cancer: TSH suppression with 2.0 to 2.2 micrograms/kg daily, to the TSH target set by risk stratification.
• Congenital hypothyroidism: start 10 to 15 micrograms/kg daily within the first 2 weeks of life.

Special groups. Pregnancy: increase the dose by 25 to 30% once pregnancy is confirmed (two extra tablets a week), keep TSH under about 2.5 mU/L, check every 4 weeks until week 20, and return to the pre-pregnancy dose after delivery. Breastfeeding: compatible. Children: dose by age and weight, with specialist care. Older adults: start low (12.5 to 25 micrograms) and target TSH at the upper reference range.

Kidney and liver impairment: no adjustment. Regional: iron deficiency anaemia and iron treatment are common, and the 4 hour gap matters. Levothyroxine does not treat iodine-deficiency goitre in euthyroid patients.

Adverse effects. Over-replacement gives palpitations, atrial fibrillation, tremor, weight loss, anxiety, insomnia and bone loss. Under-replacement leaves symptoms of hypothyroidism.

Contraindications. Untreated adrenal insufficiency (give glucocorticoid first), uncorrected thyrotoxicosis, and acute myocardial infarction for full dose starts.

Interactions. Reduced absorption with calcium, iron, proton pump inhibitors and cholestyramine. Increased clearance with rifampicin, phenytoin, carbamazepine and phenobarbital. Levothyroxine increases warfarin effect. Biotin interferes with TSH assays.

Monitoring. TSH 6 to 8 weeks after dose changes, annually when stable; free T4 when central hypothyroidism is suspected; ECG at start in older adults and cardiac disease; bone density in long-term suppression.

Referral and escalation. Myxoedema coma, pregnancy planning, thyroid cancer, central hypothyroidism, or TSH that stays abnormal despite adherence.