What is the proper investigation for a 35-year-old male patient with a nodule in the right lobe of the thyroid, low Thyroid-Stimulating Hormone (TSH), and high Thyroxine (T4) levels?

Management of Thyroid Nodule with Low TSH and High T4

For a 35-year-old male with an incidentally discovered thyroid nodule, low TSH, and high T4, a radioactive iodine scan (RAI scan) is the most appropriate initial investigation.

Diagnostic Algorithm for Thyroid Nodule with Hyperthyroidism

When a patient presents with a thyroid nodule and laboratory findings consistent with hyperthyroidism (low TSH, high T4), the diagnostic approach should follow these steps:

1. First step: Radioactive iodine scan

   • This is essential to determine if the nodule is functioning (hot) or non-functioning (cold) 1, 2
   • A functioning nodule with suppressed surrounding thyroid tissue suggests a toxic adenoma
   • This distinction is critical for treatment planning and risk assessment

2. Second step (based on RAI scan results):

   • If hot nodule: Medical therapy for hyperthyroidism may be initiated
   • If cold nodule: Proceed to FNA biopsy

3. Further evaluation:

   • Thyroid and neck ultrasound to characterize the nodule and assess for suspicious features 2
   • Assessment for clinical risk factors for malignancy

Rationale for RAI Scan as First-Line Investigation

The American College of Radiology guidelines clearly indicate that when a thyroid nodule is discovered in a patient with biochemical hyperthyroidism (low TSH), a radioactive iodine scan is the appropriate first investigation 1. This is because:

• It determines whether the nodule is autonomously functioning (causing the hyperthyroidism)
• Functioning nodules have a lower risk of malignancy compared to non-functioning nodules 3
• It guides subsequent management decisions (medical therapy vs. FNA)

The National Comprehensive Cancer Network also recommends measuring serum TSH before proceeding to FNA, as TSH results influence the diagnostic pathway 1.

Important Considerations

• Malignancy risk: While functioning nodules generally have lower malignancy risk, it's not zero. A case report documented papillary thyroid cancer presenting as a hot nodule 3, highlighting that malignancy cannot be completely ruled out even in functioning nodules.

• FNA timing: FNA should be performed after RAI scan in this clinical scenario, not as the first test, since the hyperthyroidism needs to be characterized first 2, 4.

• Follow-up considerations: If the nodule is confirmed to be a toxic adenoma, treatment options include antithyroid medications, radioactive iodine therapy, or surgery 2.

Common Pitfalls to Avoid

1. Proceeding directly to FNA without RAI scan: This misses the critical information about nodule function, which affects both malignancy risk assessment and treatment planning.

2. Immediate hemithyroidectomy: Surgery without proper characterization of the nodule and its functional status is inappropriate as first-line management.

3. Observation alone: With biochemical hyperthyroidism, active investigation and management are required rather than simple follow-up.

4. Overlooking the possibility of malignancy: Even functioning nodules can harbor malignancy, so appropriate follow-up is essential even after initial management of hyperthyroidism 3, 5.

By following this evidence-based approach, the clinician can properly characterize the nodule, assess malignancy risk, and develop an appropriate treatment plan for both the nodule and the hyperthyroidism.