Causes of Hyperthyroidism
The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goiter (including toxic adenoma), and thyroiditis. 1, 2
Primary Causes of Hyperthyroidism
1. Graves' Disease
- Accounts for approximately 70-95% of hyperthyroidism cases 2, 3
- Autoimmune disorder characterized by:
- Production of TSH receptor antibodies that stimulate the thyroid gland
- Diffusely enlarged thyroid gland (goiter)
- Distinctive ophthalmic signs (eyelid lag/retraction, exophthalmos)
- Dermal signs (localized and pretibial myxedema) 1
- More common in women than men (2% prevalence in women vs 0.5% in men) 2
2. Toxic Nodular Thyroid Disease
- Accounts for approximately 16% of hyperthyroidism cases 3
- Includes:
- Toxic multinodular goiter: Multiple autonomously functioning nodules
- Toxic adenoma: Single autonomously functioning nodule
- Nodules develop autonomous function independent of TSH regulation
- May cause local compression symptoms (dysphagia, orthopnea, voice changes) 2
3. Thyroiditis
- Causes thyrotoxicosis through destruction of thyroid follicles and release of preformed thyroid hormone
- Types include:
- Subacute (granulomatous) thyroiditis: Often follows viral infection
- Painless (silent) thyroiditis: Often autoimmune, common postpartum
- Postpartum thyroiditis: Occurs within first year after delivery
- Amiodarone-induced thyroiditis: Can be type I (iodine-induced) or type II (destructive) 1
Less Common Causes
4. Drug-Induced Hyperthyroidism
- Amiodarone: Can cause both hyperthyroidism and hypothyroidism 1, 3
- Iodine-containing medications/contrast: Can trigger hyperthyroidism in susceptible individuals
- Tyrosine kinase inhibitors and immune checkpoint inhibitors 3
5. Exogenous Thyroid Hormone
- Factitious thyrotoxicosis: Intentional or unintentional excessive intake of thyroid hormone
- Iatrogenic thyrotoxicosis: Overtreatment of hypothyroidism with levothyroxine 1
6. Rare Causes
- Trophoblastic disease: HCG-secreting tumors that can stimulate TSH receptors
- Thyroid hormone resistance: Genetic disorder with reduced tissue responsiveness to thyroid hormone
- Struma ovarii: Ovarian teratoma containing thyroid tissue that produces thyroid hormone 1
- TSH-secreting pituitary adenoma: Rare cause of central hyperthyroidism
Special Considerations
Hyperthyroidism in Pregnancy
- Graves' disease is the most common cause (95% of cases) 1
- Untreated hyperthyroidism in pregnancy increases risk of:
- Severe preeclampsia
- Preterm delivery
- Heart failure
- Miscarriage
- Low birth weight 1
Thyroid Storm
- Rare but life-threatening exacerbation of hyperthyroidism
- Medical emergency requiring immediate treatment 1
- Characterized by extreme manifestations of thyrotoxicosis
Diagnostic Approach
When hyperthyroidism is suspected, diagnosis should include:
- Laboratory testing: Low TSH with elevated free T4 and/or T3 2
- Determination of etiology:
- Clinical presentation and physical examination
- TSH receptor antibody testing (for Graves' disease)
- Thyroid ultrasonography (to identify nodules)
- Thyroid scintigraphy (if etiology unclear or nodules present) 2
Treatment Considerations
Treatment depends on the underlying cause:
- Graves' disease: Antithyroid drugs (methimazole/propylthiouracil), radioactive iodine, or surgery
- Toxic nodular goiter: Typically radioactive iodine or surgery (antithyroid drugs less effective long-term)
- Thyroiditis: Often self-limiting; symptomatic treatment with beta-blockers 4, 5
Understanding the specific cause of hyperthyroidism is crucial for determining the appropriate treatment approach and preventing complications such as cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes.