Clinical Thyroidology® for the Public

Summaries for the Public from recent articles in Clinical Thyroidology
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The use of PET imaging may change treatment and improve long-term survival of patients with thyroid cancer who have increased thyroglobulin levels and negative radioiodine scanning

CTFP Volume 14 Issue 4

Thyroid cancer has a good prognosis in general, as most patients being cured after their initial treatment. This initial treatment almost always includes surgery and, when the thyroid cancer is advanced, includes radioactive iodine therapy. The radioactive iodine works as a “magic bullet” as the cancerous cells take it up, which then destroys the cells once trapped inside. However, thyroid cancer can occasionally recur, especially if it was advanced when it was initially discovered. When it recurs, thyroid cancer can become resistant to radioactive iodine therapy if the cells no longer take up iodine. In this situation, a radioactive iodine whole body scan will also fail to identify the recurrent cancer sites. However, a positron-emission tomography (PET scan) that uses a small amount of radiolabeled glucose will often detect the cancerous areas, since recurrent thyroid cancer is often more aggressive and active, thus taking up larger amounts of glucose which is measured by the PET scan. The goal of this study was to evaluate whether the use of PET scans to detect cancerous areas improves survival in patients with recurrent thyroid cancer resistant to radioactive iodine therapy.

Schleupner MC et al 2020 Impact of FDG-PET on therapy management and outcome of differentiated thyroid carcinoma patients with elevated thyroglobulin despite negative iodine scintigraphy. Nuklearmedizin 59:356–364. PMID: 32542618.

This study included 194 patients with recurrent thyroid cancer who underwent initial treatment consisting of total thyroidectomy followed by radioactive iodine therapy between 1996 and 2014 at an institution in Germany. During follow-up, these patients had elevated serum thyroglobulin (Tg) levels without corresponding cancerous areas noted on radioactive iodine whole body scans.

Elevated Tg was defined as a baseline Tg higher or equal to 1 mg/L or a stimulated Tg higher or equal to 2 mg/L. Patients were divided into those who underwent PET scanning (PET group) and those who did not (non-PET group) at any time during follow-up. Patients were initially imaged using a single-modality PET scanner until 2004 and then a hybrid scanner combined with computed tomography (CT) was used until 2014.

Between 1996 and 2004, 42 of 70 patients (60%) underwent single-modality PET imaging, while 107 of 149 patients (86%) underwent hybrid PET/CT between 2004 and 2014. Overall, 149 patients (77%) were imaged with PET or PET/CT, while 45 patients (23%) were not. The patients in the PET group had more severe cancer and higher stimulated Tg levels at the time of study enrollment, and they already received higher radioactive iodine doses prior to participating in this study. The average Tg levels at enrolment were 3.7 vs. 3.3 mg/L, while stimulated Tg was 13.9 vs. 3.1 mg/L in the PET and non-PET groups, respectively.

During the first nine months following PET imaging, more patients underwent surgery (28% vs. 13%), while fewer patients received radioactive iodine therapy (63% vs. 82%) as compared to the non-PET group. External-beam radiotherapy was rarely used in both groups (4% vs. 2%). On long-term follow-up of up to 15 years, the patients in the PET group received all types of treatments more often as compared to the non-PET patients (radioactive iodine therapy: 54% vs. 40%, surgery: 24% vs. 11%, and external beam radiotherapy: 18% vs.2%, respectively). A total of 21% vs. 32% of patients attained complete remission, while 26% vs. 10% showed progressive disease in the PET vs. non-PET groups. The overall survival and event-free survival (time from study enrollment until recurrence was diagnosed) rates were similar in the PET and non-PET groups (15.8 vs. 16.4 years, and 11.9 vs. 13.5 years, respectively).

Patients with thyroid cancer who present with elevated serum Tg levels and negative radioiodine scanning after their initial treatment and are evaluated with PET scanning had similar long-term survival and outcomes to patients treated without PET, despite having more advanced disease at baseline. Early use of PET scanning in these patients can lead to treatment changes by identifying cancer sites that are not detectable and treatable with radioiodine, but might respond to other therapies, such as surgery and external radiation therapy. Further research is needed to evaluate the long-term clinical benefit of PET imaging in this group of patients.

— Alina Gavrila, MD, MMSc


Differentiated thyroid cancer (DTC): accounts for more than 90% of all thyroid cancers and has a high cure rate. It includes papillary and follicular thyroid cancer.

Cancer recurrence: this occurs when the cancer comes back after an initial treatment that was successful in destroying all detectable cancer at some point.

Thyroglobulin (Tg): a protein made only by thyroid cells, both normal and cancerous. When all normal thyroid tissue is destroyed after radioactive iodine therapy in patients with thyroid cancer, thyroglobulin can be used as a thyroid cancer marker, since measurable blood levels indicate recurrence.

Thyroidectomy: surgery to remove the thyroid gland. When the entire thyroid is removed it is termed a total thyroidectomy. When less is removed, such as in removal of a lobe, it is termed a partial thyroidectomy.

Radioactive iodine (RAI): this plays a valuable role in diagnosing and treating thyroid problems since it is taken up only by the normal or cancerous thyroid cells. I-131 is the destructive form used to destroy thyroid tissue in the treatment of thyroid cancer.

Radioiodine Whole Body Scan (WBS): this imaging test uses a small amount of a radioactive iodine, to take pictures of the whole body to look for thyroid cancer metastases. The radioactive iodine scans are performed under TSH stimulation, either after thyroid hormone withdrawal or after injections of recombinant human TSH (Thyrogen), and usually include measuring serum thyroglobulin levels.

Stimulated thyroglobulin testing: this test is used to measure whether there is any cancer present in a patient that has previously been treated with surgery and radioactive iodine. TSH levels are increased, either by withdrawing the patient from thyroid hormone or treating the patient with recombinant human TSH, then levels of thyroglobulin are measured.

Positron-emission tomography (PET): a nuclear medicine imaging test that uses a small amount of radiolabeled glucose to identify cancer. Since cancer cells are more active than normal cells, the cancer cells take up more of the radiolabeled glucose and show up on the PET scan. FDG-PET scans are frequently combined with CT scans to accurately identify where the cancer is located. Its role in thyroid cancer is still being studied.