Liothyronine

Liothyronine is synthetic triiodothyronine (T3), the active thyroid hormone. It has a rapid onset and a short half-life, which makes it useful when a fast effect is needed or when thyroid hormone must be withdrawn quickly (myxoedema coma as an adjunct, and preparation for radioactive iodine in thyroid cancer). It is not routinely advised for long-term hypothyroidism, because levothyroxine gives steadier levels and T3 peaks cause palpitations. Availability is limited in many regions.

Classification. Thyroid hormone, T3. Tablets 5, 10, 20 and 25 micrograms (strengths vary by market); intravenous solution in some markets.

Mechanism. Binds nuclear thyroid hormone receptors directly, regulating gene transcription for metabolic rate, cardiac output and growth, without the need for conversion.

Pharmacodynamics. Onset within hours and peak effect within 2 to 3 days orally; effect wears off within about 3 to 5 days after stopping. Raises heart rate and basal metabolic rate more abruptly than levothyroxine.

Pharmacokinetics. Oral absorption about 95%; peak 2 to 4 hours; over 99% protein bound. Half-life about 1 to 2 days. Metabolised by deiodination in liver, kidney and tissues; excreted in urine and faeces.

Myxoedema coma (emergency), as an adjunct to levothyroxine.

• Liothyronine 5 to 20 micrograms intravenously as a loading dose (use the lower end in older adults and coronary disease), then 2.5 to 10 micrograms every 8 hours, until the patient can take oral therapy. Directed by a critical care or endocrine team.
• Levothyroxine 200 to 400 micrograms intravenously is the first-line loading agent; hydrocortisone 100 mg intravenously every 8 hours is given with it until adrenal insufficiency is excluded.

Preparation for radioactive iodine or thyroid cancer imaging (withdrawal of levothyroxine).

• 20 to 25 micrograms orally two or three times daily (total 40 to 75 micrograms) for 2 to 4 weeks, replacing levothyroxine, and stopped about 2 weeks before the procedure to allow TSH to rise. Specialist directed.

Hypothyroidism, adults (second line, specialist only).

• Start 10 to 20 micrograms orally daily in two or three divided doses (5 micrograms in older adults and those with cardiac disease) and increase by 10 to 25 micrograms every 1 to 2 weeks. Usual maintenance 60 to 75 micrograms daily in divided doses; maximum about 100 micrograms daily.
• Combination levothyroxine and liothyronine is not routine; consider only through a specialist when symptoms persist despite a normal TSH on levothyroxine.

Adjustments.

• Kidney: no change.
• Liver: no change.
• Older adults and coronary disease: start 5 micrograms; avoid except in an emergency.
• Weight: no weight-based dosing in adults; children dosed by a paediatric endocrinologist.

Major warning. Not for obesity or weight loss. Doses within the replacement range do not reduce weight in euthyroid patients, and larger doses can cause serious or fatal toxicity.

Contraindications. Untreated thyrotoxicosis; uncorrected adrenal insufficiency (give hydrocortisone first); acute myocardial infarction (other than in myxoedema coma, with care); hypersensitivity.

Serious adverse effects.

• Over-replacement: palpitations, atrial fibrillation, angina, heart failure, tremor, insomnia, anxiety, weight loss, diarrhoea.
• Peaks after each dose cause variable symptoms.
• Precipitation of adrenal crisis when started before cortisol replacement in unrecognised adrenal insufficiency.
• Bone loss with prolonged excess.

Major interactions.

• Reduced absorption: calcium, iron, antacids, colestyramine, sucralfate and phosphate binders; separate by at least 4 hours.
• Increased clearance: rifampicin, phenytoin, carbamazepine, phenobarbital.
• Warfarin: effect rises as hypothyroidism is corrected; monitor INR.
• Digoxin levels fall as hypothyroidism is corrected.
• Sympathomimetics and tricyclic antidepressants: arrhythmia risk rises.
• Diabetes: insulin and oral agent requirements may rise.

Special groups.

• Pregnancy: not preferred; levothyroxine is used because foetal brain needs maternal T4.
• Breastfeeding: compatible at replacement doses.
• Children: specialist use only.
• Older adults and coronary disease: avoid except in emergencies.
• Kidney and liver impairment: no dose change.
• East Africa: rarely stocked; plan around levothyroxine, and arrange the intravenous form through hospital pharmacy for myxoedema coma where it exists.

Formulation and administration. Swallow tablets with water, in divided doses, on an empty stomach, 30 to 60 minutes before meals. For the intravenous form, give by slow intravenous injection over 2 to 5 minutes; do not mix with other solutions; discard unused portions.

Baseline. TSH, free T4, free T3, ECG, morning cortisol when adrenal disease is possible.

Monitoring.

• Heart rate, rhythm and blood pressure continuously in myxoedema coma, and at each titration step in hypothyroidism.
• TSH and free T3 before the morning dose; peak effects make later samples misleading. For combination therapy, check TSH and free T4 at 6 to 8 weeks.
• Bone density in long-term use at suppressive doses.

Dose reduction and stopping. Reduce the dose by 5 to 10 micrograms after palpitations, tremor or suppressed TSH. Stop with arrhythmia, angina or when the emergency has resolved and levothyroxine has taken over; stop about 2 weeks before radioactive iodine.

Referral and escalation. Admit suspected myxoedema coma or new arrhythmia on treatment. All long-term liothyronine use needs endocrine review.