What is the best next step for a patient with a 2x2 cm solid thyroid nodule, normal Thyroid-Stimulating Hormone (TSH) levels, and elevated Thyroxine (T4) levels?

Best Next Step: Thyroid Isotope Scan

For a patient with a 2×2 cm solid thyroid nodule, normal TSH, and elevated T4, the best next step is a thyroid isotope scan (Option C) to determine if the nodule is functioning ("hot") or non-functioning ("cold"), as this directly impacts malignancy risk and subsequent management. 1

Clinical Reasoning

This presentation suggests a hyperfunctioning ("hot") nodule causing subclinical or overt hyperthyroidism:

• Normal TSH with elevated T4 indicates autonomous thyroid hormone production, which is characteristic of toxic adenomas or toxic multinodular goiter 2
• Hot nodules have a malignancy risk of <1%, making them essentially benign 1
• Cold nodules carry a 5-15% malignancy risk and require FNA 1, 3

Why Isotope Scan Takes Priority

The isotope scan is the critical decision point that determines all subsequent management:

• If the nodule is "hot" (hyperfunctioning): FNA is not indicated because malignancy risk is negligible. Management focuses on treating hyperthyroidism with radioactive iodine, antithyroid drugs, or surgery 1
• If the nodule is "cold" (non-functioning): Proceed immediately to ultrasound-guided FNA, as this represents the standard approach for solid nodules ≥1 cm with normal/elevated TSH 1, 2

Why Not FNA First (Option A)?

While FNA is the gold standard for evaluating thyroid nodules ≥1 cm 1, 2, performing it before determining functional status would be premature:

• Guidelines recommend FNA for nodules >1 cm in euthyroid patients or those with elevated TSH 2, 1
• The elevated T4 with normal TSH suggests autonomous function, which fundamentally changes the diagnostic approach 1
• Performing unnecessary FNA on a hot nodule exposes the patient to an invasive procedure with no clinical benefit 1

Why Not Follow-Up Ultrasound (Option B)?

Surveillance is inappropriate because:

• A 2×2 cm solid nodule exceeds the size threshold where observation alone is acceptable 1
• The biochemical abnormality (elevated T4) demands active investigation, not passive monitoring 2
• Guidelines reserve surveillance for nodules <1 cm without suspicious features 2, 1

Why Not Immediate Lobectomy (Option D)?

Surgery without tissue diagnosis is premature:

• Cytological confirmation via FNA is required before surgical planning for suspected malignancy 2, 1
• If the nodule is hot, medical management (radioactive iodine) may be preferred over surgery 1
• Even for cold nodules with suspicious features, FNA guides the extent of surgery (lobectomy vs. total thyroidectomy) 2

Algorithmic Approach

Step 1: Obtain thyroid isotope scan (I-123 or Tc-99m pertechnetate) 1

Step 2a: If hot nodule → Treat hyperthyroidism (radioactive iodine, antithyroid drugs, or surgery). FNA is not indicated 1

Step 2b: If cold nodule → Proceed to ultrasound-guided FNA 1, 2

• Assess for suspicious ultrasound features: microcalcifications, marked hypoechogenicity, irregular margins, absence of peripheral halo, central hypervascularity 1
• FNA is mandatory for any solid nodule ≥1 cm that is cold on scan 1, 2

Step 3: Based on FNA cytology (Bethesda classification):

• Benign (Bethesda II): Surveillance with repeat ultrasound at 12-24 months 1
• Indeterminate (Bethesda III/IV): Consider molecular testing or diagnostic lobectomy 1, 2
• Suspicious/Malignant (Bethesda V/VI): Total or near-total thyroidectomy 2

Critical Pitfalls to Avoid

• Do not perform FNA on hot nodules – malignancy risk is <1%, making FNA unnecessary and potentially misleading 1
• Do not rely on TSH alone to exclude hyperthyroidism – this patient has normal TSH but elevated T4, indicating subclinical autonomous function 2
• Do not delay isotope scanning in favor of immediate FNA – functional status must be established first to avoid unnecessary procedures 1