Hyperthyroidism (Graves' Disease)

Hyperthyroidism

• Second half of thyroid disorders.
• Focus on pathophysiology, clinical manifestations, and management.
• Graves' disease is a key manifestation.
• Textbook readings: 492-494.

Definition

• Elevated levels of thyroid hormones.

Causes

• Most common cause: Autoimmune process linked to Graves' disease (similar to Hashimoto's in hypothyroidism).
• Higher incidence in women, familial component.

Factors Associated with Onset

• Major life change, especially in females:
  • Menopause (changes in estrogen levels)
  • Pregnancy (hormonal changes)
  • Menarche (first menstruation)
• Bacterial infections: Yersinia enterocolitica.
• Vitamin D deficiency.
• Tumor development on the pituitary or thyroid gland (influences thyroid hormone production).
• Excessive iodine availability: Increased iodine leads to increased T3 and T4 production.

Thyroid Storm

• Rare due to increased monitoring.
• Sudden increase in circulating thyroid hormone, leading to a hypermetabolic state.
• Triggers:
  • Significant illnesses
  • Pregnancy
  • Surgery
  • Sudden reduction or stopping of anti-thyroid medication.
• Can be fatal; requires rapid intervention.
• Symptoms:
  • Increased heart rate
  • Elevated blood pressure
  • Hyperthermia (elevated body temperature)

Pathophysiology of Graves' Disease

• Autoimmune basis.
• Abnormal antibodies are formed (thyroid stimulating antibodies).
• These antibodies bind to thyroid stimulating hormone (TSH) receptors on the thyroid gland.
• The thyroid stimulating antibodies compete with TSH for the receptors.
• Binding of antibodies stimulates continuous release of thyroid hormone.
• Excessive hormone release leads to clinical features of hyperthyroidism.

Clinical Manifestations

• Metabolic rate increases.
• Heart rate: Tachycardia (rapid heart rate), palpitations, angina-like sensations.
• Muscle weakness and fatigue (due to overstimulation).
• Increased gastrointestinal mobility.
• Heat intolerance.
• Increased appetite, potential weight loss (hypermetabolic state).
• Nervousness, tremors, hyperreflexia (overactive reflexes), insomnia.

Graves' Disease Specific Manifestation

• Exophthalmos: Bulging eyes due to inflammation around the eyes.
  • Autoantibody-induced inflammation.
  • Increased connective tissue behind the eye.
  • Difficulties blinking or closing eyes; requires moisture to prevent dryness.

Management of Hyperthyroidism

• Anti-thyroid medication (usually first choice).
• Radioactive isotopes (more common in America; Australia uses medicine first).
• Surgery (less common).

Radioactive Isotopes:

• Treat toxic thyroid adenoma, multi nodular goiter.
• Used for Graves' disease relapse.
• More common in older people.
• Destroys thyroid tissue, which can lead to hypothyroidism.
• Usually a one-off dose.

Surgery:

• Used when other treatments aren't suitable:
  • Pregnancy (radioactive isotopes contraindicated).
  • Allergies to anti-thyroid medicines.
  • Extremely large goiters.
  • Severe exophthalmos.

Anti-Thyroid Medicines:

• Carbimazole is the main option in Australia for patient I know.
• Reduces circulating levels of thyroid hormone.
• Prevents iodine from being incorporated into the hormone structure (T3 and T4).
• Inhibits the formation and release of thyroid hormones.
• Adverse effects:
  • Pruritus and rashes (early stages, may settle).
  • Rare but significant: Agranulocytosis (requires quick action if fever, mouth ulcers, rash, sore throat occur).
• Takes 3-4 weeks to see clinical benefits due to stored hormones in the thyroid gland.
• During pregnancy, propylthiouracil is preferred instead of carbimazole.
• Once normal thyroid function is established, dosage is reduced to the lowest possible level.
• Regular checks are needed to maintain control.

Comparison

• Comparison of Hyperthyroidism vs. Hypothyroidism: Key to differentiation is to consider the effects of 'slowing down' vs 'speeding up' of the metabolism.