For a patient who has undergone total thyroidectomy (with or without radioactive iodine ablation) for papillary thyroid carcinoma, should routine surveillance include a total body radioactive iodine scan or anti‑thyroid peroxidase antibody testing?

Surveillance of Papillary Thyroid Carcinoma: Role of Total Body Scans and Anti-TPO Antibodies

Routine total body radioactive iodine scans are NOT indicated for surveillance in low-risk papillary thyroid carcinoma patients with excellent response to therapy, and anti-thyroid peroxidase (anti-TPO) antibodies have NO role in papillary thyroid cancer surveillance. 1

Total Body Radioactive Iodine Scanning in Surveillance

When Whole-Body Scintigraphy (WBS) Is NOT Used

WBS is not utilized in low-risk patients without suspicion for recurrence and normal thyroid ultrasound. 1 The ACR Appropriateness Criteria explicitly state that if patients have excellent response to therapy with low serum thyroglobulin, additional imaging including WBS is not indicated. 1

• Low-risk patients with excellent response (thyroglobulin <0.2 ng/mL on thyroid hormone therapy or <1 ng/mL after TSH stimulation, negative thyroglobulin antibodies, and normal neck ultrasound) do not require routine WBS for ongoing surveillance. 1

• FDG-PET/CT scanning is not recommended for routine surveillance if there is no residual disease. 1

When WBS May Be Considered

In intermediate- and high-risk patients, WBS has a role in evaluating initial response to radioiodine ablation, but if there has been excellent response to therapy, WBS is usually not performed for ongoing surveillance. 1

• Consider TSH-stimulated radioiodine imaging only in patients with T3-4 or M1 at initial staging, or with abnormal thyroglobulin levels (either TSH-suppressed or TSH-stimulated), abnormal antithyroglobulin antibodies, or abnormal ultrasound during surveillance. 1

• Post-therapy WBS should be performed after RAI therapy to evaluate for residual disease, as it upstages disease in 6-13% of cases. 1

Anti-TPO Antibodies: No Role in Surveillance

Anti-thyroid peroxidase (anti-TPO) antibodies are NOT part of papillary thyroid cancer surveillance protocols. There is no mention of anti-TPO testing in any major guideline for differentiated thyroid cancer follow-up. 1

What SHOULD Be Monitored Instead

The cornerstone of biochemical surveillance is thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb), NOT anti-TPO. 1, 2

• Physical examination, TSH, and thyroglobulin measurement plus antithyroglobulin antibodies should be performed at 6 and 12 months, then annually if disease-free. 1

• At 6-12 months post-thyroidectomy, neck ultrasound together with basal thyroglobulin and thyroglobulin antibody measurements should be performed to establish disease status. 2

• The same Tg assay should be used consistently throughout follow-up to minimize inter-assay variability and improve trend reliability. 2

Optimal Surveillance Strategy

First-Line Surveillance Tool

Neck ultrasound is the first-line imaging investigation for differentiated thyroid cancer after initial therapy and includes evaluation of the thyroid bed and cervical nodes. 1

• US should be performed at 6-12 months and then periodically, depending on the patient's risk for recurrent disease and thyroglobulin status. 1

• Periodic US may not be necessary in low-risk patients who have had remnant ablation, normal initial US, and a low serum thyroglobulin. 1

• Neck ultrasound was superior to diagnostic whole-body scans in detecting recurrent papillary thyroid cancer in pediatric patients, consistent with ATA guidelines. 3

Thyroglobulin-Based Risk Stratification

For patients with thyroidectomy and RAI ablation, a low serum thyroglobulin is defined as <0.2 ng/mL on thyroid hormone therapy or <1 ng/mL after TSH stimulation. 1

• If serum thyroglobulin is elevated above the appropriate cutoff or if thyroglobulin antibodies are present and especially if they are rising, additional surveillance imaging is performed. 1

• Stimulated Tg 1-10 ng/mL: Suppress TSH with levothyroxine and continue surveillance. 1

• Stimulated Tg >10 ng/mL: Consider radioiodine therapy with 100-150 mCi and post-treatment imaging. 1

Critical Pitfalls to Avoid

Thyroglobulin Antibody Interference

Newly detectable antithyroglobulin antibodies should prompt consideration of interfering factors such as intravenous immunoglobulin treatment, which can cause passive transfer of pooled donor antibodies including TgAb. 4

• Thyroglobulin should always be measured with concurrent anti-thyroglobulin antibodies, as antibody presence makes thyroglobulin unreliable. 5

• Rising TgAb trends warrant immediate imaging and consideration of lowering TSH to <0.1 mU/L. 5

Low Postoperative Thyroglobulin Excludes Persistent Disease

The combination of nonstimulated Tg ≤0.25 ng/mL, negative TgAb, and US without metastases after thyroidectomy rules out the presence of persistent disease (including on post-therapy whole-body scan) in low-risk patients with papillary thyroid carcinoma >1 cm. 6

• None of 154 low-risk patients with these favorable markers showed ectopic uptake on post-therapy whole-body scan, and 97.4% achieved stimulated Tg ≤1 ng/mL at 9-12 months. 6

• This demonstration weakens the indication of ablation with radioactive iodine in these cases. 6

Minimal Extrathyroidal Extension

Patients with minimal extrathyroidal extension and without other adverse features, who have low nonstimulated Tg and negative neck US after thyroidectomy, do not require ablation with RAI. 7

• In 182 patients with tumors ≤4 cm and minimal extrathyroidal extension, only 2.2% developed structural recurrence during median 72-month follow-up when RAI was omitted based on low postoperative Tg. 7