What blood tests should be obtained to evaluate and monitor a patient with thyroid cancer?

Blood Tests for Thyroid Cancer Evaluation and Monitoring

Initial Diagnostic Workup

Thyroid function tests (TSH, free T4, free T3) and thyroglobulin measurement have minimal diagnostic value for detecting thyroid cancer itself, but serum calcitonin should be measured in all patients with thyroid nodules to screen for medullary thyroid cancer. 1, 2

Pre-Operative Testing

• Serum calcitonin is mandatory for all thyroid nodules, as it has higher sensitivity than fine-needle aspiration for detecting medullary thyroid cancer (5-7% of all thyroid cancers) 1, 2
• TSH should be obtained during nodule workup, though it does not distinguish benign from malignant lesions 2, 3
• Thyroglobulin measurement is not helpful for initial diagnosis and should not be ordered pre-operatively 1, 2

For suspected medullary thyroid cancer specifically, additional pre-operative tests include:

• Basal serum calcitonin and CEA 1
• Serum calcium 1
• Plasma or 24-hour urine metanephrines/normetanephrines (to exclude pheochromocytoma in hereditary cases) 1

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Post-Treatment Monitoring for Differentiated Thyroid Cancer

First Assessment (2-3 Months Post-Treatment)

Measure TSH, free T3, and free T4 solely to verify adequate levothyroxine suppressive therapy dosing. 1, 2, 3

• This assessment does not detect recurrence; it only confirms proper medication dosing 1, 2
• Target TSH varies by risk: <0.1 mIU/L for high-risk, 0.1-0.5 mIU/L for intermediate-risk, 0.5-2 mIU/L for low-risk patients 3

Critical Assessment (6-12 Months Post-Treatment)

Obtain basal serum thyroglobulin, rhTSH-stimulated thyroglobulin, and anti-thyroglobulin antibodies (TgAb) to determine disease-free status. 1, 2

• Stimulated Tg is essential—never rely on basal Tg alone at this timepoint, as stimulated values are far more sensitive for detecting residual disease 2
• Undetectable stimulated Tg (<1.0 ng/ml) with negative TgAb and normal neck ultrasound indicates complete remission with <1% recurrence risk at 10 years 1, 2
• Approximately 80% of patients will show complete remission at this assessment 1

Long-Term Follow-Up (Annually)

For patients in complete remission, measure basal serum thyroglobulin on levothyroxine therapy and TSH annually. 1, 2, 3

• No additional biochemical tests are needed unless new clinical suspicion arises 1
• The utility of repeat rhTSH-stimulated Tg testing in disease-free patients is debated, as it rarely changes management 1
• Ultrasensitive Tg assays (<0.1 ng/ml functional sensitivity) may eliminate the need for stimulation testing, though at the expense of lower specificity 1

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Post-Treatment Monitoring for Medullary Thyroid Cancer

Serum calcitonin (and CEA in specific cases) are the primary tumor markers for medullary thyroid cancer surveillance. 1

Timing and Interpretation

• Measure serum calcitonin every 6 months for the first 2-3 years, then annually 1
• Undetectable basal calcitonin after surgery strongly predicts complete remission (only 3% recurrence risk) 1
• Detectable calcitonin after pentagastrin or calcium stimulation indicates persistent disease even if basal levels are undetectable 1

Disease Localization Based on Calcitonin Levels

• Calcitonin <150 pg/ml: Limit imaging to neck ultrasound, as disease is usually locoregional 1
• Calcitonin >150 pg/ml: Mandatory search for distant metastases with comprehensive imaging (chest/neck CT, liver imaging, bone scintigraphy, PET) 1
• Calcitonin doubling time (DT) is a critical prognostic factor—shorter DT predicts worse outcomes 1

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Critical Pitfalls to Avoid

• Never order thyroglobulin for initial diagnosis of thyroid nodules—it provides no diagnostic value and wastes resources 1, 2, 3
• Always measure TgAb concurrently with Tg, as 25% of patients have interfering antibodies that can produce falsely low or undetectable results 2, 4
• Do not skip TSH-stimulated Tg at the 6-12 month assessment—basal Tg alone misses significant residual disease 2
• Avoid assuming normal thyroid function tests exclude thyroid cancer—malignancy commonly coexists with completely normal TSH, free T4, and free T3 3
• Do not order diagnostic whole-body radioiodine scans in low-risk patients with undetectable stimulated Tg and negative ultrasound, as they add no clinical information 1