What is the initial treatment for a general adult population with hyperthyroidism?

Initial Treatment for Hyperthyroidism

The initial treatment for hyperthyroidism in adults depends on the underlying cause, but for Graves' disease (the most common etiology), antithyroid drugs—specifically methimazole as first-line or propylthiouracil in specific circumstances—represent the standard initial approach, followed by definitive therapy with radioactive iodine ablation or surgery based on patient factors and treatment response. 1, 2, 3

Confirm the Diagnosis and Identify the Cause

Before initiating treatment, confirm hyperthyroidism biochemically with suppressed TSH and elevated free T4 and/or T3 levels 3, 4. The underlying cause must be established because treatment differs substantially:

• Graves' disease (70% of cases): Measure TSH-receptor antibodies, which are positive in Graves' disease 4. Patients may present with diffuse goiter, exophthalmos, or stare 3.

• Toxic nodular goiter (16% of cases): Thyroid scintigraphy shows focal areas of increased uptake 4. Patients may have compressive symptoms like dysphagia or voice changes 3.

• Thyroiditis (3% of cases): Presents with low radioiodine uptake on scintigraphy and is typically self-limited 4.

• Drug-induced (9% of cases): Consider amiodarone, tyrosine kinase inhibitors, or immune checkpoint inhibitors 4.

Initial Treatment Algorithm by Etiology

For Graves' Disease (Most Common)

Start with antithyroid drugs as initial therapy 1, 2, 3, 4:

• Methimazole is preferred over propylthiouracil in most adults due to better safety profile 2, 3
• Propylthiouracil is reserved for: first trimester of pregnancy, thyroid storm, or patients with methimazole intolerance 5, 2

Dosing for antithyroid drugs:

• Methimazole: Start 10-40 mg daily depending on severity 2
• Propylthiouracil: Initial dose 300 mg daily in divided doses (every 8 hours); may increase to 400 mg daily for severe hyperthyroidism or very large goiters 5

Treatment duration and expectations:

• Continue antithyroid drugs for 12-18 months to induce remission 6, 4
• Approximately 50% of patients experience recurrence after stopping antithyroid drugs 4
• Risk factors for recurrence include: age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 4
• Long-term treatment (5-10 years) reduces recurrence to 15% but requires ongoing monitoring 4

Add beta-blockers for symptom control:

• Beta-blockers rapidly improve cardiac symptoms (tachycardia, palpitations), neurological symptoms, and exertional dyspnea while antithyroid drugs take effect 1
• Goal is to lower heart rate to nearly normal 1

For Toxic Nodular Goiter

Radioactive iodine ablation is the treatment of choice 6, 2. Antithyroid drugs do not cure toxic nodular goiter but may be used temporarily to achieve euthyroid state before definitive therapy 6.

For Thyroiditis (Destructive Thyrotoxicosis)

Observation or supportive care is appropriate, as thyroiditis is typically mild and self-limited 3, 4. Steroids are reserved only for severe cases 4.

Definitive Treatment Options After Initial Antithyroid Drug Therapy

If antithyroid drugs fail to induce remission or hyperthyroidism recurs, proceed to definitive therapy:

Radioactive Iodine Ablation

• Most widely used treatment in the United States 2
• Well tolerated with only long-term sequela being hypothyroidism 6
• Can be used in all age groups except children, pregnancy, and lactation 6
• Avoid pregnancy for 4 months after administration 6
• May worsen Graves' ophthalmopathy—consider corticosteroid cover to reduce this risk 6

Surgery (Thyroidectomy)

• Limited but specific roles: refused radioiodine, large goiter causing compressive symptoms, or patient preference 6, 2
• Goal is subtotal or near-total thyroidectomy to cure pathology while preserving some thyroid tissue 6

Special Populations and Circumstances

Subclinical Hyperthyroidism (Low TSH, Normal T3/T4)

• Treatment recommended for: patients ≥65 years with TSH <0.10 mIU/L, symptomatic patients, or those with cardiac or osteoporotic risk factors 7, 3
• Close monitoring is essential to prevent progression to overt hyperthyroidism 7

Pregnancy

• Propylthiouracil is preferred in first trimester due to lower risk of congenital anomalies 5, 2
• Switch to methimazole after first trimester if needed 2

Thyroid Storm

• Life-threatening complication requiring urgent hospitalization with aggressive antithyroid drugs, beta-blockers, corticosteroids, and supportive care 7

Critical Pitfalls to Avoid

• Do not use antithyroid drugs as sole therapy for toxic nodular goiter—they will not cure the condition 6
• Do not delay beta-blocker initiation—cardiac symptoms require immediate control while waiting for antithyroid drugs to take effect 1
• Do not use radioiodine during pregnancy or lactation, and ensure pregnancy is avoided for 4 months post-treatment 6
• Monitor for Graves' ophthalmopathy worsening with radioiodine and consider prophylactic corticosteroids 6
• Recognize that 50% of Graves' patients will relapse after 12-18 months of antithyroid drugs—counsel patients about definitive therapy options 4

Long-Term Consequences of Untreated Hyperthyroidism

Untreated or poorly managed hyperthyroidism increases risk of:

• All-cause mortality 7, 3
• Cardiovascular events, atrial fibrillation, and heart failure 7, 3
• Osteoporosis and fractures 7, 3
• Adverse pregnancy outcomes 3
• Unintentional weight loss 3

Rapid and sustained control of hyperthyroidism improves prognosis 4.