Toxic multinodular goitre (TMNG) and thyroid antibody-positive hyperthyroidism are causes of persistent thyrotoxicosis characterized by excessive production of thyroid hormones. Definitive treatment aims to eliminate the source of excess hormone production and achieve long-term euthyroidism. Radioactive iodine therapy and thyroidectomy are the preferred treatment options, while long-term antithyroid drug therapy is generally not recommended except in selected elderly patients.

Pathophysiology

In toxic multinodular goitre, one or more autonomously functioning thyroid nodules produce thyroid hormones independent of thyroid-stimulating hormone (TSH) regulation. In thyroid antibody-positive disease, autoimmune stimulation of the thyroid gland results in excessive thyroid hormone production and persistent thyrotoxicosis.

Risk factors

• Increasing age

• Female sex

• Long-standing multinodular goitre

• Iodine deficiency or excessive iodine exposure

• Family history of thyroid disease

• Autoimmune thyroid disease

• Previous thyroid disorders

Clinical features

Patients may present with features of hyperthyroidism, including:

• Weight loss

• Palpitations

• Tremor

• Excessive sweating

• Heat intolerance

• Tachycardia

• Enlarged thyroid gland

• Frequent bowel movements

Investigations

• Serum TSH

• Free T4 (and T3 where indicated)

• Thyroid antibody testing where appropriate

• Thyroid uptake scan when indicated

• Complete blood count

• Liver function tests

• Serum calcium or parathyroid hormone after thyroidectomy

• Serial TSH monitoring following definitive treatment

Management

Non-pharmacological management

Definitive treatment consists of either:

• Radioactive iodine (¹³¹I) therapy

• Thyroidectomy

Long-term low-dose carbimazole should not be used routinely for toxic multinodular goitre or thyroid antibody-positive disease, except in selected elderly patients where definitive treatment is unsuitable.

Pharmacological management

Pre-operative preparation

Patients with overt hyperthyroidism should be rendered euthyroid before thyroidectomy by using:

• Carbimazole 15–40 mg daily in 2–3 divided doses for 4–8 weeks, followed by a maintenance dose of 5–15 mg once daily.

• A beta-blocker, such as propranolol 40 mg every 6 hours, may be added when indicated to control adrenergic symptoms.

• Pre-operative iodine should not be used in this setting.

Post-thyroidectomy management

• Measure serum calcium or intact parathyroid hormone levels after surgery.

• Administer calcitriol and oral calcium supplementation (maximum 1,200 mg elemental calcium daily in two divided doses) according to postoperative calcium or parathyroid hormone results.

• Initiate thyroid hormone replacement after thyroidectomy at approximately 1.7 µg/kg/day (0.8 µg/lb/day), adjusting the dose according to age and body weight. Elderly patients generally require lower doses.

• Monitor TSH every 1–2 months until stable, then annually.

Radioiodine therapy

Radioactive iodine therapy is recommended for persistent or recurrent hyperthyroidism following inadequate surgery for toxic multinodular goitre or thyroid antibody-positive disease.

Monitoring

• Monitor thyroid function tests (TSH and Free T4) until euthyroidism is achieved.

• Following thyroidectomy, monitor serum calcium and parathyroid hormone.

• Assess patients for symptoms of hypothyroidism after definitive treatment.

• Monitor TSH every 1–2 months after initiating thyroid hormone replacement until stable, then annually.

Complications

• Persistent or recurrent hyperthyroidism

• Hypothyroidism following definitive treatment

• Hypocalcaemia after thyroidectomy

• Recurrent laryngeal nerve injury following surgery

• Cardiac arrhythmias

• Osteoporosis

• Thyroid storm (rare)

Prognosis

The prognosis is generally excellent following definitive treatment with radioactive iodine therapy or thyroidectomy. Most patients achieve long-term control of hyperthyroidism, although lifelong thyroid hormone replacement may be required after thyroidectomy. Regular follow-up is important to detect hypothyroidism, recurrence, and postoperative complications.