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Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients

Abstract

The two major steps of iodine metabolism—uptake and organification—are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

Key Points

  • The two main biological defects in thyroid cancer tissue are a decreased uptake and a decreased organification of radioiodine

  • These defects are mainly related to decreased gene expression, but post-transcriptional mechanisms may also occur

  • TSH increases expression of thyroid-gland-specific genes, including those encoding the sodium-iodide symporter and thyroglobulin

  • Total-body scanning with radioiodine is less sensitive than the combination of serum thyroglobulin determination following TSH stimulation and neck ultrasonography for the detection of small tumor foci

  • Radioiodine treatment is effective in patients with high uptake of radioiodine who are sensitive to radiation (those who are young, those with a well-differentiated tumor, and those with small metastases)

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Figure 1: Iodine metabolism in normal thyroid cells
Figure 2: Immunostaining using an antibody against the NIS
Figure 3: Thyroid scintigraph with 123I
Figure 4: Total-body scan with 131I in a patient with multiple bone metastases in the left clavicle, dorsal and lumbar spine, ribs, and pelvic bones
Figure 5: PET scan with 18F-labeled fluorodeoxyglucose

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Correspondence to Martin Schlumberger.

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M Schlumberger has received research support from Genzyme. The other authors declared they have no competing interests.

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Schlumberger, M., Lacroix, L., Russo, D. et al. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nat Rev Endocrinol 3, 260–269 (2007). https://doi.org/10.1038/ncpendmet0449

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