Drugs For Hypothyroidism

Thyroid replacement therapy

There are two main types of thyroid hormone replacement used in clinical practice:

• Liothyronine (T3)
• Levothyroxine (T4)

Both can be administered orally or intravenously if required.

In primary hypothyroidism, dose-adjustment for both agents should be guided by regularly monitoring TSH levels. In suspected overdose, an elevated serum T3 concentration is a more reliable indicator of toxicity than serum T4 levels.

Thyroid hormone therapy must be continued throughout pregnancy, and higher doses may be required. Block and replace therapy is not recommended in pregnancy. Only small quantities of levothyroxine cross the placenta, whereas large quantities of anti-thyroid drugs cross from the mother to the infant. This can cause foetal hypothyroidism.

Patients should be advised to take thyroid replacement therapy at least 30 minutes before breakfast, tea, coffee or other medicines. This is due to the reduced absorption with ions such as calcium and other drugs, leading to risk of under dosing.

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Fig 1: Diagram of thyroid hormone regulation showing hypothalamus, pituitary gland, TRH, TSH, thyroid gland and negative feedback with T3 and T4.

Pharmacokinetic properties

Liothyronine is faster acting (few hours) but has shorter duration of action (24-48 hours), usually use in acute emergencies. It is also available as an IV preparation for treatment of myxoedema coma.

Levothyroxine is usually the treatment choice for maintenance therapy. An IV preparation is also available but not as a licensed product in the UK and must be imported. When switching from oral to IV levothyroxine, the American Association of Clinical Endocrinologists recommend an IV dose of 50–70% of the oral dose. For oral levothyroxine, the dose should be adjusted at 3-4 week intervals due to its long half-life.

Cautions

• Use cautiously in patients with cardiovascular disorders as overdose can lead to cardiac dysrhythmias and cardiac failure.
• In diabetes mellitus, thyroid hormone therapy may cause an increase in dosage requirements of insulin or oral anti-diabetic therapy such as metformin.
• Chronic excessive dosing may lead to bone resorption increasing resulting in osteoporosis
• Thyroid hormones may lower the seizure threshold

Adverse Effects

• Transient partial hair loss may occur during the first few months of therapy in children.
• Most adverse effects are due to excessive dosing and resemble symptoms of hyperthyroidism. These usually resolve after dose reduction or temporary treatment withdrawal.
• In overdose, symptoms can take up to 5 days to appear, and some patients may remain asymptomatic.

Interactions

• Levothyroxine increases anticoagulant effect of warfarin
• Thyroid hormones can reduce the blood-sugar lowering effect of antidiabetics
• Increased sensitivity to catecholamines, enhancing responses to tricyclic antidepressants
• Levothyroxine increases the metabolism of beta blockers such as propranolol, atenolol and sotalol reducing their effect
• Amiodarone and iodine containing contrast media may trigger hyper- or hypothyroidism
• Biotin can affect thyroid function tests leading to an increased TSH but normal or increased FT4.

Increased Thyroid Hormone Requirements

Higher doses may be required with:

• Amiodarone, glucocorticoids and beta-blockers (especially propranolol) which inhibit conversion of T4 to T3.
• Absorption of levothyroxine is reduced by antacids, calcium, cimetidine, iron (PO), sucralfate, orlistat and cholestyramine (administration should be separated by 4-5 hours). Liothyronine absorption is also affected by cholestyramine.
• PPIs may decrease the absorption of thyroid hormones due to increased gastric pH.
• Oestrogen, HRT and oral contraceptives
• Rifampicin, barbiturates, St John’s Wort, carbamazepine, phenytoin and primidone increase metabolism of thyroid hormones via enzyme induction
• Sertraline reduces efficacy of levothyroxine

References

1. Radioiodine for thyrotoxicosis – The Christie NHS Foundation Trust [Internet].  Available from: 146-radioiodine-treatment-for-thyrotoxicosis-nm-march-2020.pdf
2. Kumar V, Abbas A, Aster J, Robbins S. Robbins and Cotran pathologic basis of disease. 7th ed. 2005.
3. Rang H, Dale M, Flower R, Henderson G. Rang and Dale’s pharmacology. 8th ed. 2013
4. Levothyroxine 100mcg tablets – Summary of Product Characteristics (SmPC) – (emc) | 5682 accessed 11/1/26
5. Liothyronine Sodium BP 20micrograms Tablets – Summary of Product Characteristics (SmPC) – (emc) | 5905 Accessed 11/1/26
6. Liothyronine Sodium 20 micrograms Powder for Solution for Injection – Summary of Product Characteristics (SmPC) – (emc) | 2805 Accessed 11/1/26
7. Levothyroxine SERB 200 micrograms/ml solution for injection/infusion – Summary of Product Characteristics (SmPC) – (emc) | 15068 Accessed 11/1/26