Graves' hyperthyroidism is an autoimmune disorder in which thyroid-stimulating antibodies activate thyroid-stimulating hormone (TSH) receptors, causing excessive production of thyroid hormones. It is the most common cause of hyperthyroidism and may be associated with diffuse goitre and Graves' ophthalmopathy. Management aims to restore euthyroidism, relieve symptoms, and prevent recurrence and complications.

Pathophysiology

Graves' disease results from the production of thyroid-stimulating immunoglobulins that bind to and activate TSH receptors, leading to diffuse thyroid enlargement and excessive secretion of thyroid hormones. The resulting thyrotoxicosis increases metabolic activity and sympathetic nervous system stimulation.

Risk factors

• Female sex

• Family history of autoimmune thyroid disease

• Other autoimmune disorders

• Smoking

• Emotional stress

• Postpartum period

• Excess iodine exposure

• Previous history of thyroid disease

Clinical features

Patients commonly present with:

• Weight loss despite increased appetite

• Heat intolerance

• Excessive sweating

• Palpitations

• Tremor

• Anxiety and irritability

• Tachycardia

• Diffuse goitre

• Frequent bowel movements

• Graves' ophthalmopathy

Diagnostic criteria

Diagnosis is based on clinical features together with biochemical evidence of thyrotoxicosis:

• Suppressed serum TSH

• Elevated free T4 and/or T3

• Positive TSH-receptor antibodies where available

Investigations

• Serum TSH

• Free T4 and T3

• TSH-receptor antibody (TRAb) testing where available

• Complete blood count

• Liver function tests

• Thyroid uptake scan when diagnosis is uncertain

Management

Non-pharmacological management

• Educate patients regarding the disease, treatment options, and the importance of adherence.

• Encourage smoking cessation, particularly in patients with Graves' ophthalmopathy.

• Advise regular follow-up and thyroid function monitoring.

Pharmacological management

Antithyroid medicine

Carbimazole is the first-line treatment.

• Carbimazole 10–60 mg/day orally in 2–3 divided doses for the initial 4–6 weeks.

• Gradually reduce to a maintenance dose of 5–10 mg/day over 3–6 months.

• Continue treatment for approximately 12–18 months, then taper or discontinue if TSH has returned to the normal range.

Beta-blockers

For excessive sympathetic symptoms:

• Propranolol 40–120 mg/day orally as a single daily dose or in two divided doses.

OR

• Atenolol 50–100 mg orally every 12 hours.

Factors favouring antithyroid medicine

Antithyroid medicines are preferred in patients with:

• High likelihood of remission, particularly females with mild disease, small goitres, and negative or low-titre TSH-receptor antibodies.

• Elderly patients or those with comorbidities that increase surgical risk or limit life expectancy.

• Previously operated or irradiated neck.

• Moderate to severe active Graves' ophthalmopathy.

• Inability to comply with radiation safety requirements.

Radioactive iodine

Potassium iodide should be administered immediately before surgery as:

• Lugol's solution 5–7 drops (0.25–0.35 mL) three times daily for 10 days before surgery.

OR

• Saturated solution of potassium iodide 1–2 drops (0.05–0.1 mL) three times daily for 10 days before surgery.

Factors favouring radioactive iodine

• Comorbidities increasing surgical risk.

• Previously operated or externally irradiated neck.

• Lack of access to an experienced thyroid surgeon.

• Contraindication to antithyroid medicines.

• Women who are not pregnant and are not planning pregnancy within the next 4–6 months following radioactive iodine therapy.

Surgery

Thyroidectomy should be considered in patients with:

• Symptomatic compression or large goitres.

• Low uptake of radioactive iodine.

• Documented or suspected thyroid malignancy.

• Large non-functioning thyroid nodule.

• Coexisting hyperparathyroidism requiring surgery.

• Women planning pregnancy within 4–6 months.

• Moderate to severe active Graves' ophthalmopathy.

Patients undergoing thyroidectomy should be rendered euthyroid with carbimazole whenever possible.

If hyperthyroidism recurs after completion of carbimazole therapy, treatment with radioactive iodine or thyroidectomy should be considered.

Low-dose carbimazole beyond 12–18 months may be considered in patients who are not in remission and prefer continued medical therapy; however, extending treatment beyond 18 months has not been shown to improve remission rates in adults.

Monitoring

• Assess thyroid function (TSH and free T4) regularly during treatment.

• Perform complete blood count and liver function tests when clinically indicated.

• Advise patients receiving carbimazole to seek immediate medical attention if they develop fever, sore throat, or other symptoms suggestive of agranulocytosis.

• Continue monitoring after treatment to detect relapse or hypothyroidism.

Complications

• Recurrent hyperthyroidism

• Graves' ophthalmopathy

• Atrial fibrillation

• Heart failure

• Osteoporosis

• Thyroid storm

• Hypothyroidism following definitive treatment

Prognosis

Most patients achieve good control of Graves' hyperthyroidism with appropriate treatment. Antithyroid medicines induce remission in many patients, while radioactive iodine therapy and thyroidectomy provide definitive treatment for persistent or recurrent disease. Lifelong follow-up is recommended because relapse or hypothyroidism may occur after treatment.