Hyperthyroidism

Description

• Hyperthyroidism is most commonly caused by Graves disease (GD), toxic multinodular goiter (TMNG), and toxic adenoma (TA) (1),(2).
• Patients can develop thyrotoxicosis from other causes, such as subacute thyroiditis and drug-induced thyroiditis.
• Subclinical hyperthyroidism: suppressed thyroid-stimulating hormone (TSH) with normal thyroxine (T₄) and triiodothyronine (T₃)
• Thyroid storm: extreme manifestation of hyperthyroidism with acute, severe symptoms affecting multiple organ systems; up to 50% mortality (2)

Epidemiology

Etiology and Pathophysiology

• GD: autoimmune disease; characterized by autoantibodies that activate the TSH receptor (TSHr)
• TMNG: autonomous production and release of T₃ and T₄ due to constitutive activation of TSHr or somatic mutations in Gsα (1)
• TA: thyroid nodule with a somatic activating mutation in the TSHr gene, leading to autonomous overproduction of THs
• TSH-producing pituitary adenoma: rare benign pituitary tumor that secretes excess TSH, causing elevated TH (should be distinguished from TH resistance, which can show similar labs) (1)
• Gestational transient thyrotoxicosis: results from the thyroid-stimulating activity of human chorionic gonadotropin (hCG); serum hCG peaks at 9 to 12 weeks of gestation, with higher risk in twin pregnancy and in hyperemesis gravidarum.
• Iodine-induced hyperthyroidism: occurs after exposure to high iodine doses, most often from iodinated contrast media but also from seaweed or potassium iodide tablets; typically develops 3 to 10 weeks after exposure (1)
• Subacute/de Quervain thyroiditis: granulomatous giant cell thyroiditis, often preceded by an upper respiratory tract infection; viruses such as coxsackievirus, adenovirus, echovirus, and influenza have been implicated; typically benign and self-limited course
• Postpartum thyroiditis: occurs in 8–11% of pregnancies; the thyrotoxic phase is usually asymptomatic and is associated with a high risk of permanent hypothyroidism.
• Drug-induced thyroiditis: amiodarone, interferon-α, interleukin-2, lithium, immune check point inhibitors (anti-CTLA-4, anti-PD-1 antibodies), tyrosine-kinase inhibitors (sorafenib, vandetanib) (1),(2)

Risk Factors

• Female sex, iodine excess, irradiation, infections, postpartum period, drugs
• Positive family history, especially in maternal relatives
• Other autoimmune disorders
• Perturbation of gut microbiota
• Use of alemtuzumab (30% of patients develop GD)

General Prevention

• Hyperthyroidism cannot usually be fully prevented, especially autoimmune forms
• Risk can be reduced by maintaining adequate iodine intake.

Commonly Associated Conditions

• Autoimmune diseases occur in 9.7% of patients with GD (rheumatoid arthritis, pernicious anemia, systemic lupus, celiac disease, Addison disease, vitiligo) (1)
• Down syndrome