Basedow’s Disease: An Autoimmune Thyroid Disorder

1. Pathogenesis:

Basedow’s disease, also known as Graves’ disease, is an autoimmune disorder in which the body produces antibodies against components of the thyroid gland, leading to increased thyroid activity.

• Autoimmunity: The body’s immune system attacks the thyroid gland, creating antibodies against thyroid components.
• Circulating Antibodies:
  • Anti-thyroid peroxidase (TPOAb): These antibodies bind to the enzyme peroxidase, which is involved in thyroid hormone production.
  • Anti-thyroglobulin (TgAb): These antibodies bind to thyroglobulin, a protein that contains thyroid hormone.
• Thyroid-stimulating hormone receptor antibodies (TSI): These antibodies bind to the TSH receptor on thyroid cells, triggering the production and release of thyroid hormones (T3 and T4). This leads to hyperthyroidism.

2. Triggers of Basedow’s Disease:

• Postpartum: After childbirth, the immune system can be weakened, increasing the risk of developing autoimmune diseases like Basedow’s.
• Stress: Prolonged stress can suppress the immune system, increasing the likelihood of developing Basedow’s.
• Sex Steroids: Women are more susceptible to Basedow’s than men due to the influence of estrogen.
• Iodine-Rich Diet: Excessive iodine consumption can stimulate thyroid hormone production, exacerbating Basedow’s disease.
• Amiodarone: The medication amiodarone, used to treat heart rhythm disorders, contains iodine and can trigger or worsen Basedow’s.

3. Functional Symptoms of Basedow’s Disease:

• Weight Loss: Due to increased basal metabolic rate, the body burns more energy, leading to unexplained weight loss.
• Neuropsychiatric Disturbances:
  • Anxiety, restlessness, agitation.
  • Sleep disturbances.
  • Mood swings: irritability, mood lability.
  • Depression.
  • Decreased concentration.
• Thermoregulation Disturbances: The body tends to feel hot, sweats excessively, and is intolerant to heat.
• Cardiovascular Disturbances:
  • Frequent tachycardia.
  • Atrial fibrillation.
  • Isolated systolic hypertension.
  • Bounding peripheral pulses.
  • High output heart failure.
• Gastrointestinal Disturbances:
  • Diarrhea.
  • Digestive disorders.
  • Increased appetite but still losing weight.
• Neuromuscular Disturbances:
  • Fine tremor, rapid frequency: Tremor in hands, legs, head, eyelids.
  • Muscle weakness in extremities, periodic paralysis: Fatigue, muscle weakness, difficulty moving.

4. Ocular Symptoms of Basedow’s Disease:

• Proptosis (Protruding Eyes): Accumulation of substances in the eye socket causes swelling and pushes the eyeball outwards.
• Signs:
  • Stellwag’s sign: Inability to close the eyelids completely.
  • Dalrymple’s sign: Elevation of the upper eyelid resulting in widening of the palpebral fissure.
  • Von Graefe’s sign: Lag of the upper eyelid during downward gaze.
  • Moebius’ sign: Reduced convergence of the eyes causing double vision.

5. Definitive Diagnosis of Basedow’s Disease:

• Clinical Presentation: The presence of hyperthyroid symptoms, along with one or more of proptosis, pretibial myxedema, and goiter, suggests Basedow’s disease.
• Laboratory Tests:
  • TSH < 0.1 mIU/L: Decreased TSH is a hallmark of hyperthyroidism.
  • Elevated FT3, FT4: Free thyroid hormone levels are increased.
  • Elevated TRAB > 1.5 U/L: Thyroid-stimulating hormone receptor antibody levels are increased. Note: This antibody can be elevated in other conditions, so it’s not always diagnostic of Basedow’s.
  • Thyroid Scintigraphy: Increased uptake of radioactive iodine or Technetium.

6. Common Complications:

• Thyroid Storm: A life-threatening complication, potentially fatal.
• Cardiovascular Complications: Arrhythmias, heart failure.
• Malignant Exophthalmos: Rapid progression of proptosis, causing vision impairment and even blindness.
• Cachexia: Due to excessive energy depletion, the body becomes emaciated.

7. Symptoms of Thyroid Storm:

• High fever: Fever of 38-40°C (100.4-104°F).
• Severe dehydration: Vomiting, diarrhea, leading to severe dehydration.
• Cardiovascular disturbances: Rapid heart rate (over 150 beats/minute), potentially ventricular tachycardia, atrial fibrillation, atrial flutter.
• Neuropsychiatric disturbances: Confusion, agitation, coma.
• Gastrointestinal disturbances: Nausea, diarrhea, jaundice.

8. Treatment Options for Basedow’s Disease:

• Medical Treatment: Using medication to suppress thyroid hormone production.
  • Antithyroid Drugs:
    • Thiouracil group: PTU (propylthiouracil).
    • Imidazole group: Thiamazole, carbimazole.
  • Mechanism: Inhibits iodine binding to thyroglobulin, prevents the formation and coupling of DIT to form T3, T4, and inhibits the conversion of T4 to T3 peripherally.
  • Inorganic Iodine: High levels of inorganic iodine can inhibit iodine binding to thyroglobulin, reducing the coupling of DIT, MIT.
• Radioactive Iodine Therapy: Using radioactive iodine to destroy a portion of thyroid cells, reducing thyroid hormone production.
• Surgery: Removal of part or all of the thyroid gland.

9. Non-Pharmacological Treatment:

• Rest: Limiting strenuous activity, avoiding stress.
• Dietary Enhancement: Eating a balanced diet, but avoiding iodine-rich foods.

10. Drug Groups Against Thyroid Hormone Synthesis:

1. Antithyroid Drugs:

• Thiouracil group: PTU (propylthiouracil).
• Imidazole group: Thiamazole, carbimazole.
• Mechanism: Inhibits iodine binding to thyroglobulin, prevents the formation and coupling of DIT to form T3, T4, and inhibits the conversion of T4 -> T3 peripherally.

2. Inorganic Iodine:

• High levels of inorganic iodine inhibit iodine binding to thyroglobulin, reducing the coupling of DIT, MIT.

11. Treatment Attack Phase of Basedow’s Disease:

• Use high doses of antithyroid drugs for 6-8 weeks.
  • PTU: 200-400mg/day.
  • Thiamazole: 15-30mg/day.
  • Carbimazole: 30-45mg/day.
• Higher doses may be used in cases of severe hyperthyroidism or large goiters.

12. Treatment Maintenance Phase of Basedow’s Disease:

• Gradually reduce medication dosage every 1-2 months, based on clinical presentation and lab tests.
• Maintain treatment for 12-18 months.
  • PTU: 50-100mg/day.
  • Thiamazole: 5-10mg/day.
  • Carbimazole: 5-10mg/day.

13. Goals of Medical Treatment for Basedow’s Disease:

• Achieving euthyroid state:
  • Resolution of functional symptoms.
  • Weight gain.
  • Normal heart rate.
  • Normal FT3, FT4.
  • TSH may remain low.

14. Duration of Medical Treatment for Basedow’s Disease:

• 12-24 months.

15. Side Effects of Antithyroid Drugs:

• Discontinue medication if:
  • Neutrophil count (<1000/mm3) or agranulocytosis.
  • Thrombocytopenia.
  • Cholestatic jaundice.
  • Toxic hepatitis.
• Milder side effects:
  • Nausea.
  • Allergic reactions.
  • Urticaria.
  • Temporary hypothyroidism (when drug dosage is too high).

16. Indications for Lugol’s Solution:

• Rapid reduction of thyroid hormone levels: During thyroid storm.
• Preoperative preparation: Reduce bleeding during thyroid surgery.

17. Combined Medications for Basedow’s Disease:

• Beta-blockers: Reduce heart rate, lower blood pressure, improve cardiovascular symptoms.
• Corticosteroids: Used in cases of eye or skin manifestations due to Basedow’s, or during thyroid storm.
• Tranquilizers: Reduce anxiety, agitation, and sleep disturbances.

18. Indications for Radioactive Iodine Treatment:

• Elderly patients: Complications after medical treatment, recurrence after medical or surgical treatment, contraindications for surgery (severe heart failure).
• Toxic Multinodular Goiter: Removal of part or all of the thyroid gland.

19. Contraindications for Radioactive Iodine Treatment:

• Pregnancy and lactation: Radioactive iodine can affect the fetus and young children.
• Severe exophthalmos: Can worsen the condition of proptosis.
• Under 30 years of age: Relative contraindication.

20. Complications of Radioactive Iodine Treatment:

• Thyroiditis: Occurs 3-4 days after taking radioactive iodine.
• Exacerbation of exophthalmos: Increased risk of malignant exophthalmos.
• Permanent hypothyroidism: Increased risk of hypothyroidism after radioactive iodine.

21. Indications for Basedow’s Disease Surgery:

• Large goiter: Multinodular goiter, goiter buried in the mediastinum.
• Relapsing Basedow’s: After medical treatment.
• Patients who want to become pregnant soon: Thyroid surgery may be a more effective and safer treatment option for Basedow’s during pregnancy compared to medical treatment.

22. Contraindications, Precautions, and Complications of Basedow’s Disease Surgery:

Contraindications:

• Severe heart failure.
• Elderly patients (relative contraindication).

Precautions:

• Achieve euthyroid state before surgery.
• Administer Lugol’s solution for one week prior to surgery.

Complications:

• Recurrent laryngeal nerve paralysis.
• Hypoparathyroidism, hypothyroidism.

23. Treatment of Thyroid Storm:

• High doses of MMI or PTU: 400mg every 8 hours.
• Corticosteroids: 50mg Solu-Medrol.
• Beta-blockers: Reduce rapid heart rate.
• ICU Monitoring: Closely monitor patient’s condition.
• Symptomatic treatment: Fever reduction, sedation, etc.

24. Treatment of Exophthalmos:

• Elevation of the head: Reduce swelling in the eye socket.
• Instillation of normal saline or artificial tears: Reduce dryness of the eyes.
• Wearing sunglasses: Protect the eyes from strong light.
• Avoid smoking: Smoking can exacerbate proptosis.
• Corticosteroids: Oral prednisone 100mg/day or Methylprednisolone TMC 500mg/week.
• Surgery: Reduce proptosis.

Note:

• This is general information about Basedow’s disease and should not replace the advice of a doctor.
• See a doctor for prompt diagnosis and treatment.

References:

• “Internal Medicine” – Hanoi Medical University Textbook.
• “Internal Medicine” – Ho Chi Minh City University of Medicine and Pharmacy Textbook.