Workup for Nodular Hyperthyroidism
Begin with serum TSH measurement, which is the single best initial test and determines the entire diagnostic pathway for nodular hyperthyroidism. 1, 2
Initial Laboratory Assessment
- Measure serum TSH first as it directs all subsequent testing and imaging decisions 1, 2
- If TSH is low or suppressed, this confirms biochemical hyperthyroidism and indicates the need for radioiodine uptake scanning 1, 2, 3
- Measure free T4 (FT4) and free T3 (FT3) to confirm overt hyperthyroidism (elevated thyroid hormones with suppressed TSH) 3, 4
- Do not routinely measure serum calcitonin in all patients with thyroid nodules, as cost-effectiveness is not established 1
Imaging Strategy Based on TSH Results
For Low/Suppressed TSH (Hyperthyroid State)
- Perform thyroid ultrasound first to evaluate thyroid morphology, nodule characteristics, and cervical lymph nodes 1, 2
- Follow with radioiodine uptake scan (I-123 preferred over I-131) to differentiate causes of thyrotoxicosis 2, 5, 4
- The uptake scan identifies "hot" (hyperfunctioning) nodules, which are rarely malignant and do not require FNA 1, 2
- Scintigraphy helps distinguish toxic adenoma, toxic multinodular goiter, Graves' disease, and thyroiditis 2, 4
For Normal or Elevated TSH
- Proceed directly to ultrasound without radionuclide scanning 1, 2
- Ultrasound should evaluate the thyroid and central neck; lateral neck ultrasound can also be performed 1
Ultrasound Evaluation and Risk Stratification
Assess for suspicious ultrasound features that require FNA regardless of nodule functionality: 1
- Microcalcifications (highly suspicious for malignancy)
- Central hypervascularity
- Taller-than-wide shape
- Hypoechogenicity, irregular borders, absence of peripheral halo 1
Clinical Risk Assessment
Identify high-risk clinical features that increase suspicion for malignancy: 1
- Age <15 years or male gender
- History of head and neck irradiation
- Family history of thyroid cancer or associated syndromes (MEN 2A/2B, familial adenomatous polyposis, Carney complex, Cowden's syndrome)
- Firm, fixed, or rapidly growing nodule
- Associated cervical lymphadenopathy
- Vocal cord paralysis or symptoms of invasion
Fine-Needle Aspiration Decision-Making
- Hot nodules on uptake scan rarely require FNA as they are almost never malignant 1, 2
- FNA is indicated for nodules with suspicious ultrasound features even in the setting of hyperthyroidism 1
- FNA should be performed on clinically suspicious lymph nodes 6
- Ultrasound-guided FNA is preferred for accuracy 1
Additional Diagnostic Considerations
- Measure TSH-receptor antibodies if clinical features suggest Graves' disease (ophthalmopathy, diffuse goiter) 6, 3
- Thyroid peroxidase antibodies may help identify autoimmune thyroid disease 3
- Consider evaluation of vocal cord mobility if there are compressive symptoms or concern for invasion 6
Common Pitfalls to Avoid
- Never proceed directly to radionuclide uptake scan in euthyroid patients - this wastes resources and has low diagnostic value 2
- Do not use radionuclide scanning to determine malignancy in euthyroid patients with nodules 2
- Do not skip TSH measurement before selecting imaging modality, as this leads to unnecessary testing and potential radiation exposure 2
- Do not assume all hot nodules are benign - still evaluate for suspicious ultrasound features and clinical risk factors 1
Etiology Determination
The workup should distinguish between: 5, 3, 4
- Toxic adenoma (single autonomous nodule)
- Toxic multinodular goiter (multiple autonomous nodules)
- Graves' disease (diffuse uptake, TSH-receptor antibodies positive)
- Thyroiditis (low uptake, transient hyperthyroidism)
This distinction is critical as it determines definitive treatment approach (antithyroid drugs, radioactive iodine, or surgery) 5, 4