Graves’ Disease
• Robert Graves first identified the association of goiter, palpitations, and exopthalmos in 1835 • Autoimmune pathogenesis: high serum concentrations of antibodies against thyroglobulin, thyroid peroxidase, and iodide cotransporter • Antibodies bind to and either blocks or stimulates the thyrotropin receptor
Pathogenesis
• Stimulating antibodies causes thyroid hypersecretion, hypertrophy and hyperplasia of the thyroid follicles to produce diffuse goiter • Lymphocytic infiltration common • Local cytokine production by intrathyroidal inflammatory cells “fan the fire”
Predisposing factors
• Genetic factors (concordance monozygotic twins 20%) • Female sex • Whites and Asians affected equally, blacks at lower risk • Preceding stressor/illness • Smoking is weakly associated with Graves’ but is strongly associated with opthalmopathy
Clinical manifestations
• Most common symptoms are nervousness, fatigue, weight loss, palpitations, heat intolerance, increased appetite • Also seen: diarrhea, dyspnea, proximal muscle weakness, tremor, high output heart failure • With aging: weight loss and decreased appetite common, afib 20% of pts >50
Clinical manifestations specific to Graves’
• Opthalmopathy (50%):
– eye discomfort/pressure, lid lag or retraction, periorbital edema, conjunctivitis, exopthalmos, EOM dysfunction, keratitis – Infiltration of lymphocytes and macrophages – Common antigen: thyrotropin receptor expressed by orbital fibroblasts – Risk factors: smoking, age, male sex
• Dermopathy (1-2%):
– most frequent over anterolateral aspects of the shin but can occur in other areas after trauma
Diagnosis
• TSH as initial screening • Must confirm with measurement of serum free thyroxine • If thyroxine is normal, check T3 • Next step: thyroid uptake scan = diffuse uptake and enlargement • IF confusing picture (nodule on scan) can confirm by measuring thyroid peroxidase antibody (elevated in 75% of pts with Graves) or assay for thyrotropin receptor binding antibodies (80%)
Treatment
• About 20% of pts with mild symptoms will remit after one year of beta blocker therapy • 30-40% of pts treated with antithyroid drugs remain euthyroid after drug discontinued
– Choices: methimazole, PTU (inhibit thyroid peroxidase and thus synthesis of thyroid hormone) – Side effects: agranulocytosis
• Radioactive iodine
– Most cost effective treatment – Contraindicated in pregnant/breastfeeding women – May transiently worsen or precipitate opthalmopathy (pre-Rx with steroids may help)