Graves' disease

Graves’ disease is an autoimmune disorder of the thyroid in which the eyes (endocrine orbitopathy) may also be affected. The immune system produces antibodies (TSH receptor antibodies) that stimulate the thyroid to overproduce hormones.

Symptoms

  • Weight loss despite normal or increased food intake.
  • Rapid or irregular heartbeat (palpitations).
  • Sweating and hot flashes.
  • Nervousness and irritability.
  • Tremors in the hands.
  • Insomnia.
  • Bulging eyes (exophthalmos) in some patients.

Diagnosis

The diagnosis of Graves’ disease is made by measuring thyroid hormones, detecting specific antibodies, and conducting an ultrasound examination. In Graves’ disease, the patient has hyperthyroidism, characterized by low or suppressed TSH and elevated fT3 and fT4. The hyperthyroidism can reach significant levels and may even become life-threatening.

In most cases of Graves’ disease, thyroid peroxidase antibodies (TPO-AK) and thyrotropin receptor autoantibodies (TRAK) are elevated. Ultrasound examination reveals a rounded contour of the thyroid and an echo-poor internal structure. Increased thyroid blood flow can be visualized using Power Doppler Mode. This requires an ultrasound device capable of measuring vascular flow velocities using Doppler technology.

In highly active Graves’ disease, a “thyroid inferno” appearance is observed in Power Doppler Mode, indicating massive hypervascularity of the thyroid gland. In many cases, the diagnosis of acute Graves’ disease can already be made based on the symptoms of hyperthyroidism and the “flaming inferno” ultrasound image.

A scintigraphy is usually not required for diagnosis. In the scintigraphic imaging of Graves’ disease (Morbus Basedow), there is a uniform increased uptake in both thyroid lobes. However, if nodules are also observed in the ultrasound image, an additional scintigraphy must be performed to determine whether there are cold nodules in the thyroid or possibly hot nodules (indicating autonomous adenomas). The combination of Graves’ disease with autonomous adenomas is called Marine-Lenhart syndrome.

Therapy

Treatment of Graves’ Disease (Morbus Basedow):
Graves’ disease is treated with medications that inhibit thyroid hormone production, known as antithyroid drugs (thionamides). Commonly used drugs include Carbimazole, Propylthiouracil (PTU), and Thiamazole.

Common Side Effects:

  • Elevated liver enzymes (transaminases)
  • Skin rashes, itching, and hair loss
  • Occasional joint pain

Rare but Serious Side Effects:

  • Hepatitis (liver inflammation)
  • Agranulocytosis (severe drop in white blood cells)
  • Vasculitis (inflammation of blood vessels)

If serious side effects occur, therapy may need to be discontinued. Switching to another antithyroid drug can be attempted, but serious side effects often occur with all thionamides. Patients should be informed about the signs of agranulocytosis (e.g., sore throat resembling tonsillitis) and immediately undergo blood tests if symptoms appear.

Therapeutic Process:

  • Antithyroid drugs require 1–2 weeks to take effect due to the half-life of thyroid hormones (~7 days).
  • High doses are used for severe hyperthyroidism; lower doses for milder cases. Dosages are adjusted as thyroid hormone levels (fT3 and fT4) normalize, requiring frequent monitoring.
  • TSH is not reliable for therapy guidance due to its prolonged suppression.

Preferred Regimen:

  • Reduce the thionamide dose to the lowest effective level.
  • In cases of hypothyroidism during treatment, thyroid hormone supplementation is added to stabilize metabolism, requiring less frequent follow-ups (every 2–3 months).
  • Beta-blockers (e.g., Propranolol) may be used for symptom relief, reducing T4-to-T3 conversion and mitigating hyperthyroid effects.

Duration of Therapy:

  • Treatment is typically continued for 12–18 months. A shorter duration increases relapse risk, while longer treatment offers no additional benefit.
  • If relapse occurs after discontinuation, definitive therapies are recommended: radioiodine therapy or surgery.

Radioiodine Therapy:

  • A scintigraphy is performed to calculate the required radioactive iodine dose.
  • The patient is hospitalized for 2–3 days as radioactive waste must be collected.
  • Full effects may take months, often resulting in hypothyroidism, requiring lifelong thyroid hormone replacement.
  • Note: Patients with endocrine orbitopathy should opt for surgery, as radioiodine therapy can worsen eye involvement.

Surgical Treatment:

  • Complete thyroid removal is performed, leaving minimal or no residual tissue to prevent recurrence.

Thyrotoxic Crisis (Thyroid Storm):
A rare but life-threatening complication requiring immediate treatment.

Symptoms:

  • High fever (>38.5°C or 101.3°F)
  • Tachycardia (>140 bpm)
  • Hypertension
  • Gastrointestinal distress (nausea, vomiting, diarrhea)
  • Neurological symptoms (confusion, seizures, coma)
  • Sweating and exhaustion

Causes:

  • Untreated hyperthyroidism (e.g., Graves’ disease)
  • Triggers: infections, surgery, trauma, or abrupt discontinuation of antithyroid medication

Treatment:

  1. Hormone Inhibition:
    • PTU or Methimazole, with PTU preferred for its effect on T4-to-T3 conversion.
    • Potassium iodide or Lugol’s solution to block hormone release.
  2. Hormone Action Blocking:
    • Beta-blockers (Propranolol) to control heart rate and peripheral hormone effects.
    • Glucocorticoids (Hydrocortisone/Dexamethasone) to reduce T4-to-T3 conversion and inflammation.
  3. Supportive Measures:
    • IV fluids and electrolytes, antipyretics, and cooling measures.
    • Treatment of underlying triggers.

Graves’ Disease in Pregnancy:
Special care is required for both maternal and fetal health.

Treatment:

  1. Medications:
    • PTU in the first trimester (lower risk of birth defects).
    • Methimazole in the second and third trimesters (lower risk of liver damage).
    • Lowest effective doses are used, avoiding iodine supplements.
  2. Beta-blockers:
    • Used briefly for heart symptoms but with caution.
  3. Surgery:
    • Reserved for severe cases, performed in the second trimester if necessary.

Monitoring:

  • Regular thyroid function tests and fetal ultrasounds.
  • Postpartum monitoring for transient neonatal thyroid dysfunction due to maternal antibodies.

Conclusion: Graves’ disease treatment involves antithyroid drugs, definitive therapies (radioiodine or surgery), and careful monitoring to balance benefits and risks, particularly in sensitive cases like pregnancy or thyrotoxic crises.

Graves' Disease in Pregnancy:

Graves’ Disease in Pregnancy:
Special care is required for both maternal and fetal health.

Treatment:

  1. Medications:
    • PTU in the first trimester (lower risk of birth defects).
    • Methimazole in the second and third trimesters (lower risk of liver damage).
    • Lowest effective doses are used, avoiding iodine supplements.
  2. Beta-blockers:
    • Used briefly for heart symptoms but with caution.
  3. Surgery:
    • Reserved for severe cases, performed in the second trimester if necessary.

Monitoring:

  • Regular thyroid function tests and fetal ultrasounds.
  • Postpartum monitoring for transient neonatal thyroid dysfunction due to maternal antibodies.

Conclusion: Graves’ disease treatment involves antithyroid drugs, definitive therapies (radioiodine or surgery), and careful monitoring to balance benefits and risks, particularly in sensitive cases like pregnancy or thyrotoxic crises.