What is the diagnosis and management for a patient with a low Thyroid-Stimulating Hormone (TSH) level, normal free Thyroxine (T4) and Triiodothyronine (T3) levels, and a radioactive iodine uptake scan showing areas of both decreased and increased uptake?

Diagnosis: Toxic Multinodular Goiter (or Toxic Adenoma)

The most likely diagnosis is toxic multinodular goiter or a toxic adenoma causing subclinical hyperthyroidism, given the low TSH (0.21), normal free T4 and T3, and heterogeneous radioactive iodine uptake pattern showing both hot and cold areas. 1

Understanding the Clinical Picture

This presentation represents subclinical hyperthyroidism with autonomous thyroid nodule(s) producing excess hormone independent of TSH regulation. 1 The patchy uptake pattern—areas of increased uptake (hot nodules) alongside decreased uptake (suppressed normal tissue)—is pathognomonic for toxic nodular disease rather than diffuse processes like Graves' disease. 2

• The low TSH (0.21) with normal free T4/T3 definitively classifies this as subclinical hyperthyroidism, not overt disease. 1
• The heterogeneous uptake pattern on radioactive iodine scan distinguishes toxic nodular goiter from Graves' disease, which would show diffusely increased uptake. 1
• Hot nodules represent autonomously functioning thyroid tissue that suppresses TSH, causing the surrounding normal thyroid tissue to show decreased uptake. 2

Differential Diagnosis Considerations

Before finalizing the diagnosis, exclude these alternative causes of low TSH:

• Medication effects (dopamine, glucocorticoids, dobutamine) can suppress TSH without true hyperthyroidism. 1
• Nonthyroidal illness (euthyroid sick syndrome) can transiently suppress TSH, though undetectable TSH is rare unless medications are involved. 1, 3
• Recovery phase after hyperthyroidism treatment can cause transient low TSH. 1
• Assay interference from heterophilic antibodies can produce falsely low TSH readings—if clinical suspicion is low, consider measuring TSH by an alternative method. 4

Confirmatory Testing Protocol

Repeat TSH, free T4, and free T3 within 4 weeks to confirm persistent subclinical hyperthyroidism. 1 This is critical because:

• Approximately 50% of patients with TSH 0.1-0.45 mIU/L have spontaneous normalization on repeat testing. 5
• If the patient has cardiac disease, atrial fibrillation, or serious medical conditions, repeat testing within 2 weeks rather than 4 weeks. 1

Thyroid ultrasound should be performed to characterize nodule size, number, and features. 1 This helps determine:

• Whether this is a solitary toxic adenoma versus multinodular goiter
• Nodule characteristics that might warrant fine needle aspiration (though hot nodules are rarely malignant)
• Baseline measurements for monitoring progression

Management Algorithm

For TSH 0.1-0.45 mIU/L (Mild Subclinical Hyperthyroidism):

Observation with monitoring is the preferred initial approach for most patients, as no appropriately powered randomized controlled trials demonstrate benefit from treatment. 5

• Monitor TSH, free T4, and free T3 every 3-12 months. 1
• Progression to overt hyperthyroidism occurs at approximately 5% per year in those with undetectable TSH (<0.1 mIU/L), but is lower with TSH 0.1-0.45 mIU/L. 5

Consider Treatment If:

Age >65 years with cardiac risk factors or established heart disease—prolonged subclinical hyperthyroidism increases atrial fibrillation risk 3-5 fold, especially in elderly patients. 1

Postmenopausal women or those with osteoporosis risk factors—prolonged TSH suppression accelerates bone mineral density loss and increases fracture risk. 1

Symptomatic patients with palpitations, tremor, heat intolerance, or weight loss despite "normal" thyroid hormones. 1

TSH progression to <0.1 mIU/L on repeat testing, which carries higher risk of complications and progression to overt disease. 5

Treatment Options When Indicated:

Radioactive iodine ablation is the definitive treatment for toxic nodular disease and is preferred for older patients or those with cardiac disease. 1 The hot nodules concentrate iodine, allowing targeted destruction while sparing normal tissue.

Antithyroid medications (methimazole or propylthiouracil) provide temporary control but do not cure autonomous nodules—they are useful as a bridge to definitive therapy or for patients who decline radioactive iodine. 1

Surgical thyroidectomy is reserved for large goiters causing compressive symptoms, suspected malignancy, or patient preference when radioactive iodine is contraindicated. 1

Critical Pitfalls to Avoid

Do not assume all low TSH values represent true hyperthyroidism—always confirm with repeat testing and exclude medication effects and nonthyroidal illness. 1, 6

Do not overlook cardiac screening in patients >60 years—obtain ECG to screen for atrial fibrillation, as subclinical hyperthyroidism significantly increases arrhythmia risk even without symptoms. 1

Avoid iodine-containing contrast agents (CT scans with contrast) in patients with known nodular thyroid disease, as this can precipitate overt thyrotoxicosis (Jod-Basedow phenomenon). 1

Do not treat based on a single abnormal TSH value—30-60% of mildly suppressed TSH values normalize spontaneously, and unnecessary treatment carries significant morbidity. 5

Recognize that "subclinical" does not mean "benign"—prolonged TSH suppression carries real cardiovascular and bone health risks that accumulate over time, particularly in vulnerable populations. 1

Monitoring Strategy for Untreated Patients

Recheck TSH, free T4, and free T3 every 3-6 months initially, then extend to every 6-12 months if stable. 1

Obtain baseline ECG and consider annual screening for atrial fibrillation in patients >60 years. 1

Consider baseline bone density assessment in postmenopausal women with prolonged TSH suppression. 1

Educate patients about symptoms of progression to overt hyperthyroidism: palpitations, tremor, heat intolerance, unintentional weight loss, anxiety. 1