Long-term follow-up of patients thyroidectomized for thyroid papillary carcinoma (PC) with associated Graves’s disease (GD): a 131I-SPECT/CT diagnostic study

Background-Aim: The relationship of thyroid differentiated carcinomas (DTC) with GD is still unclear and it is a matter of controversy whether cancer behavior is more aggressive in this condition. The present study aimed to evaluate DTC patients with associated GD in a long-term follow-up after total thyroidectomy and radioiodine ablation. Methods: We retrospectively enrolled 30 consecutive patients with GD and PC, 16 with microcarcinoma. We also evaluated 312 euthyroid control PC patients matched for sex, age, and tumor size who underwent total thyroidectomy and radioiodine ablation during the same period as GD patients. All control cases, at surgery, did not show risk factors, such as extra-thyroid tumor extension (ETE), multifocality, and neck and distant metastases. Both GD and control patients were followed up postoperatively by 131I whole-body scan (WBS) and SPECT/CT after 185 MBq radioiodine dose using a hybrid dual-head gamma camera, and by thyroglobulin (Tg) assay; the mean follow-up period was 10 years. Results: Fourteen/30 GD patients underwent metastases during follow-up (Group 1), while 16 did not develop metastases (Group 2). Of the 14 Group 1 patients, 10/14 cases did not show risk factors at surgery, 5/10 being microcarcinomas. SPECT/CT detected 13 neck lymph node metastases, 2 of which were unclear, 1 wrongly classified, and 10 occult at WBS; Tg was undetectable or very low. Of the remaining 4/14 cases, 2 patients, 1 with microcarcinoma, had minimal ETE at surgery and SPECT/CT detected 2 neck metastases at followup occult at WBS, 1 patient with neck metastases at surgery developed further metastases only visualized at SPECT/CT, and in 1 patient with 5 lung metastases at surgery, both SPECT/CT and WBS confirmed these at follow-up; Tg was undetectable only in 1 case. Of the 16 Group 2 cases, 10 patients, 5 with microcarcinomas, had no risk factors at surgery and were negative for metastases at SPECT/CT and WBS at follow-up with Tg undetectable; of the other 6/16 patients, one had minimal ETE at surgery and the remaining 5 cases with microcarcinomas were multifocal and negative at SPECT/CT and WBS at follow-up with undetectable Tg. Of 312 PC control cases, 21 patients, 8 with microcarcinoma, developed metastases during follow-up, with SPECT/CT identifying 27 lesions, 18 of which occult at WBS; Tg was undetectable or very low in 17/21 cases. Comparing GD patient Groups with the control Group, the percentage of patients who developed metastases, among those without risk factors at surgery, was 33.3% for GD cases while it was 6.7% for control cases (p\ 0.001). Conclusions: In the present study, PC and GD patients had aggressive behavior in 46.7% of cases with neck and distant metastasis appearance at follow-up also when carcinoma characteristics were favorable and some cases also were microcarcinomas. PC patient comparison between GD and non-GD cases seems to suggest that there is an increased risk to develop metastases in GD during follow-up. Routine 131I-SPECT/CT proved useful to identify metastases also when Tg was undetectable or very low with significantly higher performance than WBS.