What causes hyperthyroidism?

Causes of Hyperthyroidism

The most common causes of hyperthyroidism are Graves' disease (70% of cases), toxic multinodular goiter (16%), toxic adenoma, and thyroiditis. 1, 2

Primary Causes of Hyperthyroidism

Autoimmune Causes

• Graves' disease: The predominant cause of hyperthyroidism worldwide
  • Affects approximately 2% of women and 0.5% of men globally 1
  • Characterized by TSH receptor antibodies that stimulate thyroid hormone production
  • Often presents with diffusely enlarged thyroid gland, exophthalmos, and pretibial myxedema 3

Nodular Thyroid Disease

• Toxic multinodular goiter: Second most common cause (16% of cases) 2

  • Results from autonomous functioning nodules producing excess thyroid hormone
  • More common in older adults and in regions with iodine deficiency

• Toxic adenoma: Single hyperfunctioning nodule

  • Can cause compression symptoms in the neck (dysphagia, voice changes) 1

Inflammatory Causes

• Thyroiditis: Inflammation of the thyroid leading to release of preformed hormones
  • Subacute (granulomatous) thyroiditis: Accounts for approximately 3% of cases 2
  • Painless (silent) thyroiditis: Common cause of transient hyperthyroidism 4
  • Postpartum thyroiditis: Occurs within a year after delivery

Secondary Causes

Medication and Substance-Induced

• Iodine-induced hyperthyroidism (Jod-Basedow phenomenon)

  • Occurs when individuals with underlying thyroid autonomy are exposed to excess iodine 5
  • Common sources: iodinated contrast media, amiodarone, dietary supplements

• Drug-induced thyrotoxicosis (9% of cases) 2

  • Amiodarone: Can cause both type I (iodine-induced) and type II (destructive) thyrotoxicosis 3, 5
  • Tyrosine kinase inhibitors
  • Immune checkpoint inhibitors

• Factitious thyrotoxicosis: Excessive ingestion of thyroid hormone 3

Other Causes

• Trophoblastic disease: Excessive production of human chorionic gonadotropin 3
• Thyroid hormone resistance: Rare genetic disorder 3
• Struma ovarii: Ectopic thyroid tissue in ovarian teratoma 3

Risk Factors for Developing Hyperthyroidism

• Female sex
• Advancing age
• Black race
• Low iodine intake
• Personal or family history of thyroid disease
• Ingestion of iodine-containing drugs (e.g., amiodarone) 3
• Type 1 diabetes (increased risk of autoimmune thyroid disease) 6
• Other autoimmune disorders 6

Clinical Presentation

Hyperthyroidism typically presents with:

• Heat intolerance
• Tachycardia
• Anxiety
• Weight loss
• Tremors
• Insomnia
• Excessive sweating
• Hypertension
• Goiter 3

Diagnostic Approach

1. Laboratory testing: Low TSH with elevated free T4 and/or T3
2. Antibody testing: TSH receptor antibodies for Graves' disease
3. Imaging:
   • Radioiodine uptake scan to differentiate causes (high uptake in Graves' disease and toxic nodules; low uptake in thyroiditis)
   • Thyroid ultrasound to evaluate nodules and thyroid morphology 3

Complications of Untreated Hyperthyroidism

• Cardiac arrhythmias (particularly atrial fibrillation)
• Heart failure
• Osteoporosis
• Adverse pregnancy outcomes
• Increased mortality 1, 2
• Thyroid storm (rare but life-threatening emergency) 3

Prevention

In areas with iodine deficiency, appropriate iodine supplementation through universal salt iodization is recommended to prevent both hypothyroidism and hyperthyroidism 3.

However, caution is needed when correcting iodine deficiency, as rapid increases in iodine intake can temporarily increase the incidence of hyperthyroidism in previously iodine-deficient populations 3.