Diagnosis and Management of Graves' Disease
The diagnosis of Graves' disease requires TSH and Free T4 testing as primary screening tools, followed by treatment with methimazole as first-line therapy for 12-18 months, with propylthiouracil reserved for first trimester pregnancy or methimazole intolerance. 1
Diagnostic Criteria for Graves' Disease
Laboratory Testing
- TSH as primary screening test
- Free T4 or Free T4 Index (FTI) to confirm diagnosis 1
- Presence of TSH receptor autoantibodies (TRAb) - these act as agonists and induce excessive thyroid hormone secretion 2
Clinical Features
- Hyperthyroidism symptoms (tachycardia, tremor, anxiety, heat intolerance)
- Goiter
- Specific findings highly suggestive of Graves' disease:
Imaging
- Orbital CT or MRI if ophthalmopathy is present to evaluate extraocular muscle involvement 1
- Thyroid ultrasound may be helpful for diagnosis 3
Treatment Options
First-Line Treatment: Antithyroid Medications
Methimazole
- Preferred first-line agent 1, 4
- Starting dose: 10-40 mg daily based on severity
- Treatment duration: 12-18 months
- Goal: Maintain FT4 or FTI in high-normal range using lowest possible dose 1
- Monitoring:
- Every 2-3 weeks initially
- Every 4-6 weeks until euthyroid
- Watch for side effects: agranulocytosis, hepatotoxicity, vasculitis 1
Propylthiouracil
- Reserved for specific situations only:
- Higher risk of severe liver injury compared to methimazole 1
Adjunctive Treatment
- Beta-blockers (propranolol or atenolol) for symptomatic relief of:
- Tachycardia
- Tremor
- Anxiety
- Heat intolerance
- Continue until thyroid hormone levels normalize 1
Second-Line/Definitive Treatments
Radioactive Iodine (RAI)
- Contraindications:
- Pregnancy
- Active/severe orbitopathy 1
- Precautions:
- Steroid prophylaxis for patients with mild/active orbitopathy
- No breastfeeding for four months after treatment
- May worsen thyroid eye disease in 15-20% of patients 6
- Results in permanent hypothyroidism requiring lifelong levothyroxine 2, 6
Thyroidectomy
- Should be performed by experienced high-volume thyroid surgeon
- Preparation with methimazole and potassium iodide solution
- Indications:
- Potential complications:
- Hypoparathyroidism
- Vocal cord paralysis 6
Special Considerations
Graves' Ophthalmopathy
- Present in approximately 25% of Graves' disease patients 3
- Requires specialized treatment independent of hyperthyroidism management
- Ocular lubricants for exposure related to eyelid retraction and proptosis
- Early endocrine referral warranted 1
- For moderate-to-severe and active ophthalmopathy:
- IV glucocorticoids (more effective than oral)
- Combination of IV methylprednisolone and mycophenolate sodium recommended as first-line 7
Pregnancy
- Propylthiouracil preferred in first trimester
- Methimazole preferred in second and third trimesters
- Goal: Maintain FT4 in high-normal range using lowest possible dose
- Close monitoring as thyroid dysfunction may diminish as pregnancy proceeds 1
- Some women may opt for definitive therapy before pregnancy to avoid potential teratogenic effects of antithyroid drugs 6
Pediatric Patients
- Longer treatment course (24-36 months) recommended
- Methimazole preferred over propylthiouracil due to liver injury risk 1
Monitoring and Follow-up
- Regular monitoring of thyroid function tests
- Patient education about medication side effects
- Immediate reporting of symptoms like sore throat, fever, rash, or liver dysfunction
- Long-term monitoring essential even after successful treatment 1
Common Pitfalls to Avoid
- Failure to monitor for antithyroid medication side effects
- Inadequate follow-up
- Overlooking drug interactions
- Inappropriate use of RAI in pregnancy or patients with orbitopathy 1
- Treating patients with both adrenal insufficiency and hyperthyroidism without addressing adrenal insufficiency first (can precipitate adrenal crisis) 1