What is the treatment algorithm for hyperthyroidism?

Hyperthyroidism Treatment Algorithm

Beta-blockers (atenolol or propranolol) should be initiated immediately for symptomatic relief in all hyperthyroid patients, followed by methimazole as the preferred thionamide for definitive treatment, with the specific regimen determined by disease severity. 1

Initial Symptomatic Management

All patients with hyperthyroidism require beta-blocker therapy regardless of severity to control tachycardia, tremor, heat intolerance, and other adrenergic symptoms. 1

• Atenolol or propranolol are the specifically recommended agents 1
• For patients with atrial fibrillation secondary to hyperthyroidism, beta-blockers are the preferred rate control agents 1
• If beta-blockers are contraindicated, use nondihydropyridine calcium channel antagonists (diltiazem or verapamil) as alternatives 1

Critical caveat: Beta-blockers provide only symptomatic relief and should never be used as monotherapy for definitive treatment—they must be combined with antithyroid drugs. 1

Definitive Treatment: Thionamide Selection

Methimazole (MMI) is the preferred antithyroid drug over propylthiouracil (PTU) for most patients. 2, 3, 4

Why Methimazole is Superior:

• More effective: MMI normalizes thyroid hormones significantly faster than PTU 5, 2, 6
• Better dosing: Once-daily administration (vs. three times daily for PTU) due to longer half-life 3, 4
• Fewer adverse effects: Particularly lower hepatotoxicity risk compared to PTU 2, 4
• Better efficacy data: MMI 15 mg daily normalized thyroid hormones in 77% of patients vs. only 19% with PTU 150 mg daily at 12 weeks 5

When to Use Propylthiouracil Instead:

• First trimester of pregnancy (weeks 0-16): PTU is preferred due to MMI's teratogenic effects 7, 4
• Pre-pregnancy planning months: Switch to PTU before conception 4
• Thyroid storm: PTU has the additional benefit of blocking peripheral T4-to-T3 conversion 7
• Severe MMI allergy or intolerance 3

Treatment Algorithm by Severity

Grade 1 (Mild Symptoms):

• Beta-blocker monotherapy for symptomatic relief 1
• Add methimazole 15 mg once daily for definitive treatment 1, 2

Grade 2 (Moderate Symptoms):

• Beta-blocker plus hydration/supportive care 1
• Methimazole 15-30 mg once daily depending on initial free T4 levels 2
  • Use 15 mg for mild-moderate disease (FT4 <7 ng/dL) 2
  • Use 30 mg for more severe disease (FT4 ≥7 ng/dL) 2

Grade 3-4 (Severe/Life-Threatening):

Immediate hospitalization with endocrine consultation is mandatory. 1

Combination therapy required: 1

• Beta-blockers (high-dose)
• Thionamides (methimazole 30 mg or PTU 300 mg in divided doses)
• Corticosteroids (critical for blocking T4-to-T3 conversion—do not delay) 1
• SSKI (saturated solution of potassium iodide) 1

Critical pitfall: Corticosteroids must not be delayed in thyroid storm, as they are essential for blocking peripheral conversion of T4 to T3. 1

Monitoring Requirements

TSH and free T4 must be checked every 4-6 weeks during dose titration for all patients on antithyroid drugs. 1

Specific Monitoring for Propylthiouracil:

Due to severe hepatotoxicity risk, patients on PTU require vigilant monitoring for: 7

• Fever, loss of appetite, nausea, vomiting
• Right upper abdominal pain or tenderness
• Dark (tea-colored) urine
• Pale stools
• Jaundice (yellowing of skin or eyes)
• Stop PTU immediately and contact physician if any of these occur 7

White Blood Cell Monitoring:

Both thionamides can cause agranulocytosis (usually within first 3 months). 7

• Instruct patients to report fever, chills, or sore throat immediately 7

Dosing Specifics

Methimazole:

• Mild-moderate disease: 15 mg once daily 5, 2, 6
• Severe disease (FT4 ≥7 ng/dL): 30 mg once daily 2
• Once-daily dosing is effective and improves compliance 5, 3, 4

Propylthiouracil:

• Standard dosing: 150-300 mg daily divided into 3 doses (every 8 hours) 7, 5
• Thyroid storm: Higher doses may be required 7
• Must be taken three times daily due to shorter half-life 3

Mechanism of Action Considerations

• Both MMI and PTU inhibit thyroid hormone synthesis but do not inactivate existing circulating hormones 7, 8
• PTU uniquely blocks peripheral conversion of T4 to T3, making it advantageous in thyroid storm 7
• Neither drug interferes with exogenous thyroid hormone administration 7, 8

Common Pitfalls to Avoid

1. Never use beta-blockers alone for definitive treatment—they only provide symptomatic relief 1
2. Do not delay corticosteroids in severe hyperthyroidism or thyroid storm 1
3. Switch from MMI to PTU before pregnancy or in first trimester due to teratogenicity 7, 4
4. Do not use once-daily PTU dosing—it is significantly less effective than once-daily MMI and requires three-times-daily administration 5, 3
5. Monitor liver function closely with PTU—it carries higher hepatotoxicity risk than MMI, including risk of liver failure and death 7, 2