graves'%20disease
GRAVES' DISEASE
Graves' disease is an autoimmune disorder that results into overproduction of thyroid hormones.
Thyrotoxicosis signs and symptoms include hyperactivity, irritability, insomnia, dysphoria, sweating, heat intolerance, palpitations, weakness, fatigue, weight loss despite increased appetite, diarrhea, steatorrhea polyuria, decreased libido, tachycardia, tremor, goiter, alopecia, gynecomastia, eyelid lag or retraction and rarely periodic paralysis.
Clinical features in thyrotoxic patient that suggests Graves's disease are ophthalmopathy, thyroid dermopathy, thyroid acropachy, diffuse goiter, antibodies to thyroid peroxidase or thyroglobulin and thyroid radionuclide scan demonstrating a diffuse goiter.

Principles of Therapy

Treatment methods will depend on:
  • Clinical presentation
  • Age of patient
    • <50 yr: Antithyroid agents - 1st-line agent
    • ≥50 yr: Radioactive iodine - 1st-line agent
  • Regional preferences
    • Europe & Asia: Antithyroid agents - 1st-line agent
    • North America: Radioactive iodine - 1st-line agent
  • Clinician preference
    • Patient’s input

Pharmacotherapy

Antithyroid Agents
  • Usually 1st-line agent for patients <50 yr, & in Europe & Asia
  • Preferred therapy in pregnant women & childn, patients w/ high likelihood of remission, elderly, or others w/ comorbidities increasing surgical risk or w/ limited life expectancy
  • Effects: 30-40% of patients remain euthyroid 10 yr after antithyroid treatment
    • Remission is most likely to occur in patients w/ mild hyperthyroidism & small goiters
    • If remission is not achieved, it is unlikely that a 2nd course will bring on remission
    • 10-15% of patients become hypothyroid 15 yr after treatment
  • Usually takes 2-3 wk to control symptoms
    • May use beta-blockers to control symptoms during this period, but not always needed
Carbimazole & Methimazole
  • Actions: Inhibit thyroid peroxidase & hence the synthesis of thyroid hormone
  • Fewer tablets are needed for initial treatment compared w/ PTU
  • In most circumstances, preferred thionamide antithyroid agent than PTU
Propylthiouracil (PTU)
  • Actions: Inhibits thyroid peroxidase & hence the synthesis of thyroid hormone, & blocks the extrathyroidal deiodination of T4 to T3
    • Preferred over Methimazole during 1st trimester of pregnancy, thyrotoxic crises & in patients w/ adverse reactions w/ Methimazole that are not candidate for radioiodine therapy or surgery 
Beta-blockers
  • Eg Propranolol, Atenolol, Metoprolol
  • Should be given to elderly patients w/ symptomatic thyrotoxicosis & to other thyrotoxic patients w/ heart rate >90 beats/min or coexistent cardiovascular disease
    • Should be considered in all patients w/ symptomatic thyrotoxicosis
  • Decreases heart rate, systolic blood pressure, muscle weakness & tremor
  • Shows improvement in the degree of irritability, emotional lability & exercise tolerance

Thyrotoxic Crisis

  • A life-threatening exacerbation of hyperthyroidism
  • Usually preceded w/ acute illness (eg infection, trauma, stroke), radioactive iodine treatment, or surgery
Signs & Symptoms
  • Fever
  • Seizures
  • Mental confusion
  • Coma
  • Vomiting
  • Diarrhea
  • Jaundice
Non-pharmacological Therapy
  • Treat underlying cause
  • Close monitoring & supportive care
  • Cooling, IV fluids
Pharmacological Therapy
  • Important to reduce thyroid hormone synthesis
    • Large doses of PTU
    • 1 hr after 1st dose of PTU administer: inorganic iodide
  •  Beta-blocker to reduce adrenergic effects eg tachycardia
  • Glucocorticoids may be given
  • Antibiotics may be required if infection is present
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