How do you differentiate and treat thyroiditis versus Graves' disease?

Differentiating and Treating Thyroiditis versus Graves' Disease

Radioactive iodine uptake (RAIU) scan is the most definitive test to differentiate thyroiditis from Graves' disease, with thyroiditis showing decreased uptake and Graves' disease showing increased uptake. 1, 2

Diagnostic Differentiation

Clinical Features

• Graves' Disease:

  • Persistent hyperthyroidism
  • Often has associated ophthalmopathy (exophthalmos)
  • Diffuse goiter, possibly with thyroid bruit
  • May have pretibial myxedema
  • Typically gradual onset of symptoms

• Thyroiditis:

  • Transient hyperthyroidism followed by hypothyroidism or return to normal
  • Often has neck pain and tenderness (especially in subacute thyroiditis)
  • May have recent viral illness (subacute thyroiditis)
  • Usually more abrupt onset of symptoms
  • No ophthalmopathy or pretibial myxedema

Laboratory Testing

• Both conditions:

  • Low TSH, elevated free T4 and/or T3 during thyrotoxic phase

• Specific tests for differentiation:

  • TSH receptor antibodies (TRAb): Positive in Graves', negative in thyroiditis 2
  • Thyroid-stimulating antibodies (TSAb): Positive in Graves', negative in thyroiditis 3
  • Anti-thyroid peroxidase (TPO) antibodies: May be positive in both but more common in Hashimoto's thyroiditis 2
  • Erythrocyte sedimentation rate (ESR): Typically elevated in subacute thyroiditis, normal in Graves'

Imaging

• Radioactive iodine uptake (RAIU) scan:

  • Graves' disease: Increased uptake (diffusely) 1
  • Thyroiditis: Decreased uptake 1

• Thyroid ultrasound with Doppler:

  • Graves' disease: Increased blood flow 1
  • Thyroiditis: Decreased blood flow 1
  • Sensitivity 95% and specificity 90% for Doppler US compared to 90% sensitivity and 100% specificity for RAIU 1

Treatment Approaches

Thyroiditis Treatment

1. Subacute (painful) thyroiditis:

   • Mild symptoms: NSAIDs for pain and inflammation
   • Moderate to severe symptoms: Short course of corticosteroids (prednisone 40mg daily with taper over 2-4 weeks)
   • Symptomatic thyrotoxicosis: Beta-blockers (e.g., propranolol) for symptom control
   • Subsequent hypothyroid phase: May require temporary levothyroxine replacement

2. Silent/painless thyroiditis:

   • Symptomatic thyrotoxicosis: Beta-blockers for symptom control
   • Subsequent hypothyroid phase: May require temporary or permanent levothyroxine replacement
   • Close monitoring every 2-3 weeks to catch transition to hypothyroidism 1

3. Key point: Antithyroid drugs (methimazole, propylthiouracil) are NOT effective for thyroiditis as the condition is due to release of preformed thyroid hormone, not increased production

Graves' Disease Treatment

Three main options:

1. Antithyroid drugs:

   • First-line in many cases, especially younger patients
   • Methimazole (preferred) or propylthiouracil (PTU)
   • 12-18 month course leads to remission in ~50% of patients 3
   • Monitor for rare but serious side effects: agranulocytosis, hepatotoxicity (most common in first 90 days) 3
   • Initial dose: Methimazole 10-30mg daily based on severity
   • Monitor thyroid function every 4-6 weeks initially 1

2. Radioactive iodine (RAI):

   • Definitive therapy, destroys thyroid tissue
   • Results in permanent hypothyroidism requiring lifelong levothyroxine
   • Caution: May worsen thyroid eye disease in 15-20% of patients 3
   • Contraindicated in pregnancy

3. Surgery (near-total thyroidectomy):

   • Preferred for patients with:
     • Large goiters
     • Suspicious thyroid nodules
     • Moderate to severe thyroid eye disease
     • Coexisting hyperparathyroidism
   • Results in permanent hypothyroidism requiring lifelong levothyroxine
   • Potential complications: hypoparathyroidism, vocal cord paralysis 3

4. Adjunctive therapy:

   • Beta-blockers for symptomatic relief until euthyroidism achieved

Treatment Algorithm

1. Confirm diagnosis: RAIU scan and/or TRAb testing
2. For thyroiditis:
   • Symptomatic treatment (beta-blockers, NSAIDs or steroids if painful)
   • Monitor for hypothyroid phase every 2-3 weeks
   • Temporary levothyroxine if hypothyroidism develops
3. For Graves' disease:
   • Age <40, first episode, small goiter: Consider antithyroid drugs trial
   • Age >40, large goiter, thyroid nodules, or eye disease: Consider definitive therapy (RAI or surgery)
   • Pregnancy or planning pregnancy: Antithyroid drugs (PTU in first trimester, methimazole thereafter)
   • Severe thyroid eye disease: Surgery preferred over RAI

Common Pitfalls and Caveats

• Misdiagnosis: Failing to differentiate between the conditions leads to inappropriate treatment (antithyroid drugs ineffective in thyroiditis)
• Incomplete evaluation: Not performing RAIU scan when diagnosis is unclear
• Overlooking transition: Missing the hypothyroid phase of thyroiditis
• Medication monitoring: Not monitoring for antithyroid drug side effects, especially in first 90 days
• Pregnancy considerations: Not switching from methimazole to PTU in first trimester of pregnancy
• Eye disease: Not considering the impact of RAI on thyroid eye disease
• Follow-up: Inadequate monitoring of thyroid function during and after treatment

Remember that some patients may experience a shift from Graves' disease to Hashimoto's thyroiditis over time, requiring a change in management approach from treating hyperthyroidism to treating hypothyroidism 4, 5.