From the Guidelines
When evaluating thyroid nodules, the initial laboratory assessment should include a thyroid-stimulating hormone (TSH) test, as it is crucial in determining the risk of malignancy and guiding further management. The TSH result is particularly important because suppressed TSH levels may indicate a hyperfunctioning nodule, which typically has lower malignancy risk, while elevated TSH is associated with higher risk of malignancy 1.
Key Laboratory Tests
- TSH test: essential in initial evaluation to assess thyroid function and determine the risk of malignancy
- Free T4 and free T3: should be measured if TSH is abnormal to further assess thyroid function
- Calcitonin testing: may be considered for patients with family history of medullary thyroid cancer or multiple endocrine neoplasia, as it is a reliable tool for diagnosing medullary thyroid cancer 1
- Thyroglobulin levels: not routinely recommended for initial nodule evaluation but useful for monitoring patients after thyroid cancer treatment
- Thyroid antibodies (anti-TPO, anti-thyroglobulin): should be checked if autoimmune thyroid disease is suspected
Importance of Imaging and Fine Needle Aspiration
Laboratory testing alone cannot definitively diagnose or exclude thyroid cancer, so correlation with imaging, such as ultrasound, and possibly fine needle aspiration (FNA) is essential for comprehensive nodule evaluation 1. FNA should be performed in any thyroid nodule >1 cm and in those <1 cm if there is any clinical or ultrasonographic suspicion of malignancy. The results of FNA are very sensitive for the differential diagnosis of benign and malignant nodules, although there are limitations, such as inadequate samples and follicular neoplasia 1.
Molecular Testing
Molecular testing for thyroid nodules, such as BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations, may be considered, as the presence of any mutation is a strong indicator of cancer, with approximately 97% of mutation-positive nodules having a malignant diagnosis at histology 1. However, this should be used in conjunction with other diagnostic tools, such as ultrasound and FNA, to guide management.
From the Research
Thyroid Nodule Labs
- The initial assessment of thyroid nodules involves measuring serum thyroid stimulating hormone (TSH) levels to exclude functional thyroid nodules (FTN) 2, 3, 4.
- However, the sensitivity of TSH is low, and normalized TSH (nTSH) levels can improve diagnostic efficiency by removing thyroid peroxidase antibody (TPOAb) interference 4.
- A study found that nTSH levels had a higher sensitivity, specificity, and accuracy than traditional TSH values in accessing FTN 4.
- TSH measurement is not an appropriate screening test for autonomous functioning thyroid nodules (AFTNs), as a significant proportion of AFTNs present with normal TSH levels 5.
- Thyroid scan remains the gold standard for detecting AFTN and should be considered before performing fine-needle aspiration cytology (FNAC) 5.
- Fine-needle aspiration biopsy is the single most important procedure for differentiating benign from malignant thyroid nodules 2, 3, 6.
- Molecular analysis of indeterminate FNA samples has potential to better discriminate benign from malignant nodules and thus guide management 2, 6.
- Ultrasound and scintigraphy are useful adjuncts in the preoperative and postoperative management of patients with thyroid cancer 2, 3, 6.