Thyroid hormones: levothyroxine, liothyronine

Question 1

Thyroid hormones: levothyroxine, liothyronine

Clinical pharmacology
Common indications

Answer 1

• Primary hypothyroidism.
• Hypothyroidism secondary to hypopituitarism.

Question 2

Thyroid hormones: levothyroxine, liothyronine

Mechanisms of action

Answer 2

• The thyroid gland produces thyroxine (T4), which is converted to the more active triiodothyronine (T3) in target tissues. Thyroid hormones regulate metabolism and growth
• Deficiency of these hormones causes hypothyroidism, with clinical features including lethargy, weight gain, constipation and slowing of mental processes
• . Hypothyroidism is treated by long-term replacement of thyroid hormones, most usually as levothyroxine (synthetic T4)
• Liothyronine (synthetic T3) has a shorter half-life and quicker onset (a few hours) and offset (24–48 hours) of action than levothyroxine

Question 3

Thyroid hormones: levothyroxine, liothyronine

Important adverse effects

Answer 3

• adverse effects of levothyroxine are usually due to excessive doses, so are predictably similar to symptoms of hyperthyroidism
• These include gastrointestinal (e.g. diarrhoea, vomiting, weight loss), cardiac (e.g. palpitations, arrhythmias, angina) and neurological (e.g. tremor, restlessness, insomnia) manifestations

Question 4

Thyroid hormones: levothyroxine, liothyronine

Warnings

Answer 4

• Thyroid hormones increase heart rate and metabolism. They can therefore precipitate cardiac ischaemia in people with coronary artery disease
• In hypopituitarism, corticosteroid therapy must be initiated before thyroid hormone replacement to avoid precipitating an Addisonian crisis.

Question 5

Thyroid hormones: levothyroxine, liothyronine

Important interactions

Answer 5

• absorption of levothyroxine is reduced by antacids, calcium or iron salts, administration of these drugs needs to be separated by about 4 hours
• An increase in levothyroxine dose may be required in patients taking cytochrome P450 inducers, e.g. phenytoin, carbamazepine
• Levothyroxine-induced changes in metabolism can increase insulin or oral hypoglycaemic requirements in diabetes mellitus and enhance the effects of warfarin

Question 6

Thyroid hormones: levothyroxine, liothyronine

Practical prescribing
Prescription

Answer 6

• starting dose of 50–100 micrograms daily is recommended, except in the elderly or people with cardiac disease, who should start on 25 micrograms daily
• Liothyronine is available for IV administration in emergency care. It should be prescribed only after consultation with senior and specialist colleagues

Question 7

Thyroid hormones: levothyroxine, liothyronine

Monitoring

Answer 7

• Thyroid function tests should be measured 3 months after starting treatment or a change in dose
• thyroid stimulating hormone (TSH) is the main guide to dosing. It is elevated due to loss of negative feedback of T4 on the pituitary.
• With adequate levothyroxine replacement, TSH should return to normal or low-normal concentrations