What are the causes of hyperthyroidism?

Causes of Hyperthyroidism

Graves disease is the most common cause of hyperthyroidism, accounting for 95% of cases in pregnancy and approximately 2% prevalence in women and 0.5% in men globally. 1, 2

Primary Causes of Hyperthyroidism

Autoimmune Causes

• Graves disease is the predominant autoimmune cause, characterized by circulating immunoglobulins that bind to and stimulate the thyrotropin (TSH) receptor, resulting in sustained thyroid overactivity 3, 4
• Hashimoto thyroiditis can paradoxically cause hyperthyroidism during its thyrotoxic phase, though it more commonly causes hypothyroidism 1

Toxic Nodular Disease

• Toxic multinodular goiter develops when multiple thyroid nodules acquire autonomous function and produce excess thyroid hormone independent of TSH stimulation 1, 5
• Toxic adenoma (solitary toxic nodule) represents a single hyperfunctioning nodule that autonomously produces thyroid hormone 5, 6
• Functional thyroid nodules are identified as a common cause, particularly in older adults 1

Thyroiditis-Related Causes

• Subacute thyroiditis causes transient hyperthyroidism through hormone leakage from an inflamed thyroid gland rather than increased synthesis 1, 6
• The thyrotoxic phase of thyroiditis typically resolves spontaneously and may be followed by transient hypothyroidism 4

Iatrogenic and Drug-Induced Causes

• Amiodarone-induced thyrotoxicosis occurs in approximately 2% of patients receiving this antiarrhythmic medication, with higher incidence in patients with prior inadequate dietary iodine intake 7
• Amiodarone can cause hyperthyroidism either through its release of large amounts of inorganic iodine or through direct toxic effects on the thyroid 7
• Radioactive iodine therapy and thyroidectomy for previous hyperthyroidism can paradoxically lead to iatrogenic thyroid dysfunction 1
• Exogenous thyroid hormone ingestion (factitious thyrotoxicosis) causes thyrotoxicosis without true hyperthyroidism 6, 4

Less Common Causes

• Iodine-induced hyperthyroidism can occur with excessive iodine intake, particularly in patients with underlying thyroid nodules 1, 4
• Thyrotropin-secreting pituitary tumors are rare causes that stimulate thyroid hormone production through excess TSH 6
• Choriocarcinoma can produce substances with TSH-like activity 6

Risk Factors for Developing Hyperthyroidism

Female sex is the strongest demographic risk factor, with women affected 4-10 times more frequently than men. 1

Demographic and Genetic Factors

• Advancing age increases risk, particularly for toxic nodular disease 1
• Black race is associated with higher risk of low TSH levels 1
• Family history of thyroid disease significantly increases risk 1

Medical History Factors

• Previous hyperthyroidism increases risk, possibly due to ablation therapy leading to iatrogenic dysfunction 1
• Type 1 diabetes is associated with increased risk 1
• Down syndrome carries elevated risk 1
• Goiter presence increases likelihood of developing hyperthyroidism 1
• External-beam radiation to the head and neck area 1

Environmental and Lifestyle Factors

• Low iodine intake paradoxically increases risk of hyperthyroidism from toxic nodular disease 1
• Cigarette smoking or tobacco smoke exposure increases risk, particularly for Graves disease 1
• Low blood selenium levels may contribute to thyroid dysfunction 1

Clinical Significance

Untreated hyperthyroidism causes serious morbidity and mortality through cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. 2 In pregnant women specifically, inadequately treated hyperthyroidism increases risk for severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight in neonates 1. Thyroid storm, though rare, represents a medical emergency with potential for death if not aggressively managed 1, 7.