Introduction

Thyrotoxicosis is a clinical condition characterised by excess thyroid hormone activity, due to increased levels of triiodothyronine (T3) and thyroxine (T4) in the body. This leads to an overactive metabolism, accelerating various physiological processes and affecting multiple organ systems.¹

Causes of thyrotoxicosis

There are several reasons why the thyroid gland may become overactive and produce too much thyroid hormone. Some of the main causes include:

1. Graves' disease (an Autoimmune condition): This is the most common cause of an overactive thyroid. This occurs when the body's immune system mistakenly attacks the thyroid, making it produce too much thyroid hormone. It affects about 4 in every 5 people with hyperthyroidism.
2. Thyroid growths (Nodules or tumours)
   • Toxic thyroid adenoma- A small, non-cancerous lump (tumour) in the thyroid that produces too much hormone
   • Toxic multinodular goitre- Overgrowth of multiple lumps (nodules) in the thyroid, leading to excessive hormone production
3. Certain medications: some medicines, like aniodarone (used to treat irregular heartbeats), can cause the thyroid to become overactive
4. Pregnancy-related causes: high levels of the hormone called human chorionic gonadotropin (hCG) during early pregnancy, multiple pregnancies (twins/triplets), or a molar pregnancy (an abnormal growth in the womb) can lead to excess thyroid hormones
5. Pituitary gland tumour: a non-cancerous tumour in the pituitary gland, can lead to excessive thyroid hormone production
6. Thyroid inflammation (Thyroiditis): The swelling or inflammation of the thyroid can cause it to temporarily release too much thyroid hormone
7. Thyroid cancer: In very rare cases, a cancerous tumour in the thyroid can affect how much hormone the gland produces

Hyperthyroidism can have different causes, so it’s important to see a doctor for proper diagnosis and treatment.^2,3

Types of antithyroid medications

Thioureylenes/Thionamides

Mechanism of action

Thionamides, including carbimazole, methimazole, and propylthiouracil (PTU), work by reducing thyroid hormone levels through the following mechanisms:

• Inhibition of thyroperoxidase (TPO): This enzyme is responsible for adding iodide to thyroglobulin, a crucial step in the synthesis of thyroid hormones (T4 and T3)
• Prevention of thyroxine (T4) formation: by blocking TPO, thionamides limit the production of thyroid hormones
• Inhibition of peripheral T4 to T3 conversion (specific to PTU): PTU additionally inhibits 5'-deiodinase, preventing the activation of T4 into its more potent form, T3

Indications for use

Thionamides are used to reduce thyroid hormone levels in patients with thyrotoxicosis, including Graves’ disease.
Carbimazole is the preferred choice for treating Graves’ disease, except in the following cases:

• First trimester of pregnancy (due to potential fetal risks)
• Thyroid storm (where PTU is preferred due to its additional inhibition of T4 to T3 conversion)
• Patients with adverse reactions to carbimazole

Dosing and administration

• Carbimazole is commonly used for patients with Graves’ disease, unless contraindicated
• PTU is preferred in thyroid storm and in the first trimester of pregnancy

Side effects and risks

Major side effects:

• Agranulocytosis (0.1–0.5%)
  • It can occur at any time and at any dose
  • It is potentially fatal, requiring immediate discontinuation if suspected
• Severe hepatitis (0.1–0.2%)
  • It is more commonly associated with PTU
• Cholestasis (rare)
  • It is more frequently seen with carbimazole
• Vasculitis (rare)
• Severe polyarthritis

Minor side effects:

• Skin reactions (4–6%) such as rashes

Special considerations

• Monitor for agranulocytosis: patients should report symptoms like fever or sore throat immediately
• Hepatotoxicity risk with PTU: liver function should be monitored
• Carbimazole should be avoided in early pregnancy; PTU is preferred in the first trimester

Short-range emission of radioactive iodine

Mechanism of action

Radioactive iodine (¹³¹I) is used in the treatment of hyperthyroidism. It is taken up by thyroid cells and incorporated into thyroglobulin, similar to natural iodine. The isotope emits gamma and beta rays, with beta rays responsible for short-range emission, leading to localised cell destruction. This cytotoxic effect gradually reduces thyroid hormone production. In most cases, hypothyroidism develops as a result of thyroid cell destruction.

Clinical use

It is used to reduce thyroid hormone levels in conditions like thyrotoxicosis. However, radioactive iodine therapy is becoming less popular due to alternative treatment options.

Adverse effects

• Nausea is a potential side effect following the treatment

Special precautions

• Strict contact precautions are necessary after treatment to limit radiation exposure to others
• It is not suitable for:
  • Pregnant or breastfeeding women (risk of fetal or neonatal exposure)
  • Children (due to long-term risks and potential developmental concerns)

Surgery for treating hyperthyroidism

Effectiveness

• Surgery is equally as effective as radioactive iodine (¹³¹I) therapy or antithyroid drugs in treating Graves’ disease
• The choice of treatment depends on a shared decision between the patient and physician

Reasons for choosing surgery

• Avoiding radioactive iodine therapy due to personal preference or concerns
• Avoiding side effects associated with antithyroid medications
• Needing a rapid reduction of hyperthyroidism, especially in severe cases
• Presence of a very large goitre causing airway obstruction, making surgery a necessary intervention

Surgical procedure & outcome

A total thyroidectomy is typically performed, which results in hypothyroidism, requiring lifelong thyroid hormone replacement therapy.

Adjunctive therapy in thyrotoxicosis

Adjunctive therapy is used alongside antithyroid drugs in cases of severe thyrotoxicosis, such as thyroid storm, to provide symptom relief and enhance treatment effectiveness.

1. Iodine or Glucocorticoids: it is used in severe cases of thyrotoxicosis to quickly reduce thyroid hormone levels
2. Beta-adrenoceptor antagonists (e.g., propranolol): propranolol is commonly used to provide rapid relief from adrenergic symptoms, including tremors, palpitations, heat intolerance, nervousness and so on. While it does not directly reduce thyroid hormone production, propranolol inhibits the conversion of T4 to T3, contributing to better symptom control. It is often used while waiting for antithyroid drugs to take full effect
3. Corticosteroids
   • Can inhibit the conversion of T4 to T3, though they do not have direct antithyroid effects
   • Provides relief in cases like thyroiditis, especially when inflammation and pain are present
   • Used in Graves’ disease to manage thyroid eye disease
4. NSAIDs
   • Used in subacute thyroiditis to help manage inflammation and pain^4,5

Summary

Thyrotoxicosis is a condition caused by excess thyroid hormone (T3, T4), leading to an overactive metabolism. Common causes include Graves' disease, thyroid nodules, certain medications, pregnancy-related factors, pituitary tumours, thyroiditis, and rarely, thyroid cancer.

Treatment options include:

• Antithyroid medications (Thionamides): Carbimazole and PTU inhibit thyroid hormone production, with PTU preferred in thyroid storm and early pregnancy
• Radioactive iodine therapy (¹³¹I): Destroys thyroid cells but can cause hypothyroidism
• Surgery (Total thyroidectomy): Is an option for severe cases, large goitres, or when other treatments fail, requiring lifelong hormone replacement

Adjunctive therapies include beta-blockers (e.g., propranolol) for symptom control, iodine, corticosteroids, and NSAIDs for inflammation. Proper diagnosis and tailored treatment are essential for effective management.

FAQ’s

What is the first-line treatment for thyrotoxicosis?

In most cases, the first-line treatment for thyrotoxicosis is antithyroid medications(thionamides) such as carbimazole (preferred in most cases), propylthiouracil (PTU) (preferred in thyroid storm and the first trimester of pregnancy). These medications work by inhibiting thyroid hormone production. Along with this, beta blockers (e.g, propranolol) can be used to control symptoms like palpitations, tremors, and anxiety. 

Which is better, PTU or carbimazole?

The primary treatment for hyperthyroidism is typically carbimazole, while propylthiouracil (PTU) serves as a second-line option. PTU is used when carbimazole is unsuitable, such as during pregnancy, breastfeeding, or when surgery and radioactive iodine therapy are not viable options.⁶