What are the causes of hyperthyroidism?

Causes of Hyperthyroidism

Graves' disease is the most common cause of hyperthyroidism, accounting for approximately 70-95% of cases, followed by toxic nodular goiter (16%) 1, 2.

Primary Causes of Hyperthyroidism

1. Autoimmune Causes

• Graves' disease: The predominant cause, characterized by:
  • TSH receptor antibodies (TRAb) stimulating the thyroid gland
  • Distinctive ophthalmic signs (eyelid lag/retraction)
  • Dermal signs (localized and pretibial myxedema) 1
  • Diffusely enlarged thyroid gland 3

2. Nodular Thyroid Disease

• Toxic multinodular goiter: Autonomously functioning nodules that develop in the thyroid
• Toxic adenoma: Single hyperfunctioning nodule 4
• May cause local compression symptoms (dysphagia, orthopnea, voice changes) 3

3. Thyroiditis (causing thyrotoxicosis without true hyperthyroidism)

• Painless (silent) thyroiditis: Excessive passive release of preformed thyroid hormones 4
• Subacute granulomatous thyroiditis (3% of cases) 2
• Postpartum thyroiditis: Occurs within the first year after delivery

4. Drug-Induced Causes (9% of cases) 2

• Iodine-induced: Excess iodine intake in susceptible individuals
• Medication-induced:
  • Amiodarone
  • Tyrosine kinase inhibitors
  • Immune checkpoint inhibitors

5. Other Causes

• Factitious hyperthyroidism: Excessive ingestion of thyroid hormones 5
• Thyroid storm: Rare, severe acute exacerbation of hyperthyroidism, a medical emergency 1

Diagnostic Approach

1. Clinical suspicion based on symptoms:

   • Tremors, nervousness, insomnia
   • Excessive sweating, heat intolerance
   • Tachycardia, hypertension
   • Unintentional weight loss
   • Diarrhea
   • Goiter 1, 3

2. Biochemical confirmation:

   • Suppressed TSH
   • Elevated free T4 (FT4) or free T4 index (FTI)
   • Elevated free T3 (FT3) in some cases 6, 2

3. Etiologic diagnosis:

   • TSH-receptor antibodies (primary marker for Graves' disease)
   • Thyroid peroxidase antibodies
   • Thyroid ultrasonography
   • Radionuclide thyroid scintigraphy (especially if nodules are present) 2, 3

Clinical Implications

Untreated hyperthyroidism can lead to:

• Cardiac arrhythmias and heart failure
• Osteoporosis
• Adverse pregnancy outcomes (severe preeclampsia, preterm delivery)
• Increased mortality 1, 3

Treatment Considerations

Treatment depends on the underlying cause:

• Graves' disease: Antithyroid drugs (12-18 months course), radioactive iodine, or surgery
• Toxic nodular goiter: Primarily radioactive iodine or surgery (antithyroid drugs have high relapse rates)
• Thyroiditis: Symptomatic management, sometimes glucocorticoids 6, 2

Hyperthyroidism requires prompt diagnosis and treatment to prevent complications that can significantly impact morbidity, mortality, and quality of life.