What causes hyperthyroidism?

Causes of Hyperthyroidism

The most common causes of hyperthyroidism are Graves' disease (70% of cases), toxic nodular goiter (16%), thyroiditis (3%), and medication-induced hyperthyroidism (9%). 1

Primary Causes of Hyperthyroidism

1. Autoimmune Disorders

• Graves' disease: The predominant cause of hyperthyroidism worldwide, affecting approximately 2% of women and 0.5% of men globally 2
  • Characterized by TSH receptor antibodies that stimulate thyroid hormone production
  • Often presents with diffusely enlarged thyroid gland, exophthalmos, and pretibial myxedema

2. Thyroid Nodule Disorders

• Toxic multinodular goiter: Autonomous functioning nodules that produce excess thyroid hormone 3
• Toxic adenoma: Single hyperfunctioning nodule producing excess thyroid hormone 4
  • May cause local compression symptoms including dysphagia, orthopnea, or voice changes 2

3. Inflammatory Conditions

• Thyroiditis: Inflammation of the thyroid leading to release of preformed thyroid hormones 5
  • Subacute (granulomatous) thyroiditis: Often following viral infection
  • Painless (silent) thyroiditis: Common cause of postpartum thyroid dysfunction 4
  • Hashimoto's thyroiditis: Can cause transient hyperthyroidism during inflammatory phase 3

Secondary Causes

1. Medication-Induced

• Iodine-containing medications: Amiodarone (can cause both hyper- and hypothyroidism) 3
• Tyrosine kinase inhibitors 1
• Immune checkpoint inhibitors 1
• Excessive thyroid hormone intake: Factitious thyrotoxicosis from intentional or accidental overdose 6

2. Iodine-Related

• Iodine-induced hyperthyroidism: Occurs in iodine-deficient areas when iodine intake suddenly increases 3
• Iodine deficiency: Paradoxically can lead to autonomous thyroid nodules that are unresponsive to TSH control 3

3. Other Causes

• Trophoblastic disease: Rare cause due to high levels of human chorionic gonadotropin 3
• Thyroid hormone resistance: Genetic disorder affecting thyroid hormone receptors 3
• Struma ovarii: Rare ovarian teratoma containing thyroid tissue 3

Clinical Presentation

Common symptoms of hyperthyroidism include:

• Anxiety, nervousness
• Insomnia
• Excessive sweating
• Heat intolerance
• Tachycardia, hypertension
• Unintentional weight loss
• Diarrhea
• Palpitations 3, 2

Diagnostic Approach

1. Laboratory testing:

   • Low TSH with elevated free T4 and/or free T3 indicates overt hyperthyroidism
   • Low TSH with normal free T4/T3 indicates subclinical hyperthyroidism 2

2. Etiology determination:

   • TSH receptor antibody testing (positive in Graves' disease)
   • Thyroid ultrasound to evaluate for nodules or diffuse enlargement
   • Radioiodine uptake scan to differentiate between causes:
     • High uptake: Graves' disease, toxic nodules
     • Low uptake: Thyroiditis, exogenous thyroid hormone 3, 5

Complications

Untreated hyperthyroidism can lead to:

• Cardiac arrhythmias (particularly atrial fibrillation)
• Heart failure
• Osteoporosis
• Adverse pregnancy outcomes
• Increased mortality 2
• Thyroid storm (medical emergency) in approximately 1% of pregnant women with hyperthyroidism 3

Treatment Considerations

Treatment depends on the underlying cause:

• Graves' disease: Antithyroid drugs (methimazole preferred), radioactive iodine ablation, or surgery
• Toxic nodular goiter: Typically radioactive iodine or surgery, as antithyroid drugs have high relapse rates
• Thyroiditis: Supportive care, beta-blockers for symptom control, sometimes corticosteroids 1, 5

Subclinical hyperthyroidism treatment is recommended for:

• Patients older than 65 years
• Those with or at risk for heart disease or osteoporosis
• Patients with persistent TSH <0.1 mIU/L 7