Why is a whole body scan using radioactive iodine (I-131) not recommended for an adult patient with Medullary Thyroid Carcinoma (MTC) after total thyroidectomy?

Why Radioactive Iodine (I-131) Whole Body Scan is Not Recommended for Medullary Thyroid Carcinoma

Radioactive iodine (I-131) whole body scanning has no role in medullary thyroid carcinoma because MTC cells arise from parafollicular C-cells that lack the sodium-iodide symporter and therefore do not concentrate iodine. 1

Fundamental Biological Difference

MTC is fundamentally different from differentiated thyroid cancer (DTC) because it originates from calcitonin-producing C-cells rather than thyroid follicular cells. 1

• C-cells lack TSH receptors and do not possess the cellular machinery to uptake radioactive iodine, making both I-131 scanning and radioiodine therapy ineffective 2, 3
• This is in stark contrast to papillary and follicular thyroid cancers, where follicular cells retain iodine-concentrating ability and I-131 scanning is a cornerstone of surveillance 4

Guideline Recommendations

The American College of Radiology explicitly states that whole-body scintigraphy has no role in the imaging of MTC, and MTC cells do not uptake iodine. 1

• The National Comprehensive Cancer Network recommends against using radioiodine therapy or TSH suppression in MTC patients, as these cells lack TSH receptors entirely 2
• The American College of Endocrinology advises against radioiodine therapy for MTC because these tumors do not concentrate iodine 3
• In-111 somatostatin receptor scintigraphy, radioiodine uptake, and DOTATATE scanning similarly have no role, as pentetreotide is insensitive for MTC 1

Appropriate Imaging Modalities for MTC

Instead of radioiodine scanning, surveillance relies on tumor marker monitoring (calcitonin and CEA) combined with anatomic imaging. 2, 3

For Post-Thyroidectomy Surveillance:

• Neck ultrasound is the first-line imaging modality for early follow-up and routine surveillance 1, 3
• Contrast-enhanced CT of neck, chest, and abdomen when calcitonin levels exceed 150 pg/mL, as this threshold indicates high risk of distant metastases 1, 3, 5
• FDG-PET/CT when calcitonin exceeds 1,000 pg/mL or doubling time is less than 12 months, though sensitivity is only 59% overall and increases to 75% in aggressive disease 1, 3
• MRI of abdomen for liver metastases evaluation (49% detection rate versus 27% for PET) 1
• Bone scintigraphy or MRI of spine for patients with bone pain or calcitonin levels >150 pg/mL 1

Clinical Pitfalls and Caveats

A critical pitfall is assuming that all thyroid cancers behave like differentiated thyroid cancer and ordering I-131 scans reflexively after thyroidectomy. 1

• Postoperative management focuses on calcitonin and CEA levels measured at 2-3 months post-surgery, with doubling times calculated from sequential measurements to predict disease aggressiveness 2, 3
• Undetectable postoperative calcitonin indicates biochemical cure; detectable levels indicate persistent disease even when imaging is negative until calcitonin approaches 150 pg/mL 5
• Unlike DTC, levothyroxine is given only for replacement to maintain normal TSH levels, not for suppression 2, 3

Rare Exception in Literature

While one small 2006 study suggested potential benefit of radioactive iodine affecting neighboring parafollicular cells through radiation from adjacent follicular cells in patients with C-cell hyperplasia confined to the thyroid 6, and a 2023 systematic review identified case reports of responses 7, these findings are not supported by current guidelines and represent isolated observations with high risk of bias. 7 The American College of Radiology and National Comprehensive Cancer Network maintain that I-131 has no established role in MTC management 1, 2, 3.

Management Algorithm

For an adult post-total thyroidectomy MTC patient:

1. Measure serum calcitonin and CEA at 2-3 months postoperatively 2, 3
2. If calcitonin is undetectable: Follow with calcitonin every 6 months for 2-3 years, then annually, with neck ultrasound 2, 3
3. If calcitonin is detectable but <150 pg/mL: Neck ultrasound every 6-12 months 3
4. If calcitonin ≥150 pg/mL: Comprehensive metastatic survey with contrast-enhanced CT of neck/chest/abdomen, liver imaging (MRI preferred), and bone imaging 1, 2, 3
5. If calcitonin >1,000 pg/mL or doubling time <12 months: Consider FDG-PET/CT 1, 3

Never order I-131 whole body scanning for MTC surveillance or treatment planning. 1, 2, 3