What is the appropriate treatment approach for a patient with hyperthyroidism?

Treatment of Hyperthyroidism

The appropriate treatment for hyperthyroidism depends on the underlying etiology: for Graves' disease, first-line therapy is antithyroid drugs (methimazole preferred, propylthiouracil only if methimazole is not tolerated), radioactive iodine, or surgery; for toxic nodular goiter, radioactive iodine or surgery is preferred; and for thyroiditis-induced thyrotoxicosis, supportive care with beta-blockers is typically sufficient as the condition is self-limited. 1, 2, 3

Initial Diagnostic Workup

Before initiating treatment, establish the specific cause of hyperthyroidism:

• Confirm biochemical hyperthyroidism: Low TSH with elevated free T4 and/or T3 1, 3
• Check TSH receptor antibodies if Graves' disease is suspected (positive in Graves' disease) 4
• Perform thyroid scintigraphy if nodules are present or etiology is unclear—diffuse uptake indicates Graves' disease, focal uptake indicates toxic nodular disease, and low/absent uptake suggests thyroiditis 4, 1
• Look for pathognomonic signs: Ophthalmopathy or thyroid bruit are diagnostic of Graves' disease 4, 3

Treatment by Etiology

Graves' Disease (Most Common Cause)

Antithyroid Drugs (First-Line Option):

• Methimazole is preferred over propylthiouracil due to better safety profile 5, 1, 3
• Propylthiouracil should be reserved for patients intolerant of methimazole or during first trimester of pregnancy due to risk of severe liver injury 6
• Standard course: 12-18 months, though long-term treatment (5-10 years) reduces recurrence from 50% to 15% 2
• Predictors of recurrence after stopping antithyroid drugs: Age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 2

Radioactive Iodine (Definitive Therapy):

• Resolves hyperthyroidism in >90% of patients 3
• Hypothyroidism develops in most patients within 1 year post-treatment 3
• Avoid in pregnancy, lactation, and children; pregnancy should be avoided for 4 months after administration 7
• May worsen Graves' ophthalmopathy—consider corticosteroid cover to reduce this risk 7

Surgery (Subtotal or Near-Total Thyroidectomy):

• Indicated when radioiodine is refused, large compressive goiter is present, or rapid definitive treatment is needed 7, 3
• Treatment of choice for patients with compressive symptoms 3

Toxic Nodular Goiter (Toxic Multinodular Goiter or Toxic Adenoma)

• Radioactive iodine is the treatment of choice 7, 2
• Surgery (thyroidectomy) is an alternative, especially for compressive symptoms 3
• Antithyroid drugs do NOT cure toxic nodular disease but can be used for temporary control before definitive therapy 7

Thyroiditis-Induced Thyrotoxicosis

Supportive Care (Self-Limited Condition):

• Beta-blockers for symptomatic relief: Atenolol 25-50 mg daily or propranolol, titrated to heart rate <90 bpm 4
• Hyperthyroid phase typically resolves within weeks, often transitioning to hypothyroidism 4
• Monitor thyroid function every 2-3 weeks to catch transition to hypothyroidism 4
• High-dose corticosteroids are NOT routinely required 4
• Initiate levothyroxine if patient becomes hypothyroid (elevated TSH with low FT4) 4

Severity-Based Management Algorithm

Grade 1 (Asymptomatic or Mild Symptoms):

• Continue monitoring or initiate antithyroid drugs 4
• Beta-blocker for symptomatic relief if needed 4
• Close monitoring every 2-3 weeks 4

Grade 2 (Moderate Symptoms, Able to Perform ADL):

• Consider holding immune checkpoint inhibitors if applicable 4
• Endocrine consultation 4
• Beta-blocker, hydration, and supportive care 4
• For persistent thyrotoxicosis >6 weeks, refer to endocrinology for additional workup and possible medical thyroid suppression 4

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

• Hold immune checkpoint inhibitors until symptoms resolve 4
• Mandatory endocrine consultation 4
• Consider hospitalization 4
• Beta-blocker, hydration, and supportive care 4
• Inpatient endocrine consultation can guide use of additional therapies including steroids, SSKI (saturated solution of potassium iodide), or thionamides (methimazole or propylthiouracil), and possible surgery 4

Subclinical Hyperthyroidism

Treatment is recommended for:

• Patients >65 years old 8
• Persistent TSH <0.1 mIU/L 4, 8
• Presence of osteoporosis, atrial fibrillation, or cardiovascular disease 1, 8

For TSH 0.1-0.45 mIU/L:

• Repeat testing within 2 weeks if atrial fibrillation or cardiac disease present 4
• Otherwise, repeat within 3 months and monitor at 3-12 month intervals 4

For TSH <0.1 mIU/L:

• Repeat measurement with FT4 and T3 within 4 weeks 4
• Shorter interval if cardiac symptoms present 4

Critical Pitfalls to Avoid

• Do not use propylthiouracil as first-line therapy due to risk of severe hepatotoxicity requiring liver transplantation 6
• Do not give radioactive iodine during pregnancy or lactation 7
• Do not assume antithyroid drugs will cure toxic nodular disease—they only provide temporary control 7
• Do not miss the transition from thyrotoxicosis to hypothyroidism in thyroiditis—requires close monitoring every 2-3 weeks 4
• Do not overlook Graves' ophthalmopathy—physical examination findings should prompt early endocrine referral 4