A 55-year-old man comes to the office for follow-up. Six months ago, the patient was diagnosed with papillary thyroid cancer and underwent total thyroidectomy, followed by radioactive iodine treatment. Since then, he has been taking levothyroxine and has had no issues. The patient has no other medical conditions and does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits. Physical examination shows a well-healed surgical incision with no palpable neck masses or enlarged cervical lymph nodes. Laboratory testing shows significantly elevated serum thyroglobulin concentration compared with the previous level 6 months ago. Which of the following best explains the observed laboratory finding in this patient?

Question

A 55-year-old man comes to the office for follow-up.  Six months ago, the patient was diagnosed with papillary thyroid cancer and underwent total thyroidectomy, followed by radioactive iodine treatment.  Since then, he has been taking levothyroxine and has had no issues.  The patient has no other medical conditions and does not use tobacco, alcohol, or illicit drugs.  Vital signs are within normal limits.  Physical examination shows a well-healed surgical incision with no palpable neck masses or enlarged cervical lymph nodes.  Laboratory testing shows significantly elevated serum thyroglobulin concentration compared with the previous level 6 months ago.  Which of the following best explains the observed laboratory finding in this patient?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d8c7_eb13_bc81_e9c3a6afa7e6_MD0003_00 Thyroglobulin (Tg) is the precursor to active thyroid hormones (T3 and T4) and is produced by normal thyroid tissue or differentiated (ie, papillary, follicular) thyroid cancer. Most Tg is stored in the thyroid gland, but some is released into the circulation. Patients such as this one who have undergone a total thyroidectomy and radioactive iodine treatment should have no residual normal thyroid tissue; therefore, a rising Tg level in these patients is likely due to recurrent differentiated thyroid cancer. Patients who have undergone thyroidectomy for differentiated thyroid cancer require levothyroxine (T4) supplementation for 2 reasons: Levothyroxine replaces thyroid gland function. Levothyroxine suppresses pituitary release of TSH (negative feedback). Because TSH stimulates thyroid tissue growth, levothyroxine supplementation to suppress TSH (ie, by causing a mildly hyperthyroid state) may help prevent thyroid cancer recurrence. In some patients, a "stimulated" Tg level can also be obtained to evaluate for recurrence. This test measures the Tg level after withdrawing levothyroxine supplementation (to increase pituitary release of TSH) or after giving recombinant TSH. If there is recurrent cancer, the increased TSH will cause increased Tg release from the cancer cells. (Choice A) Radioactive iodine causes radiation-induced destruction of thyroid cells and is used as an adjuvant treatment for thyroid cancer. Because the iodine can be taken up by other cells, adverse effects include sialadenitis (salivary gland infection), dry mouth, and pulmonary fibrosis. Tg levels would not be affected. (Choice B) Tumor neoantigens are attractive targets for cancer immunotherapy. However, increased immunologic response (ie, increased antibody formation) toward tumor cells should decrease persistent/recurrent disease and therefore decrease serum Tg. (Choices C and D) Excess thyroid hormone replacement, which leads to enhanced negative feedback to the pituitary, would be expected to decrease, rather than increase, Tg levels in patients who have Tg-producing cells (including in this patient with likely recurrent thyroid cancer). Educational objective: Thyroglobulin is produced only by thyroid tissue (either normally functioning or malignant). Serum thyroglobulin measurements are used as a tumor marker once the normally functioning thyroid tissue is removed. References: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. (http://www.ncbi.nlm.nih.gov/pubmed/26462967) Novel targeted therapies and immunotherapy for advanced thyroid cancers. (http://www.ncbi.nlm.nih.gov/pubmed/29455653)

A 55-Year-Old Man Comes to the Office for Follow-Up