What is the next step in managing a patient with multifocal bilateral papillary thyroid carcinoma, who has undergone total thyroidectomy, radioactive iodine (I-131) therapy, and has persistently detectable but low thyroglobulin levels, with recent imaging studies showing nodules concerning for recurrence and lymph nodes concerning for metastatic disease?

From the Guidelines

In this case of a patient with multifocal bilateral papillary thyroid carcinoma who has persistently detectable thyroglobulin levels despite negative imaging studies, I would recommend continued surveillance with thyroglobulin monitoring every 6 months and annual neck ultrasound, as well as maintaining TSH suppression therapy with levothyroxine, aiming for a TSH level between 0.1-0.5 mIU/L. Given the patient's history and the results of the recent PET scan in March 2023, which did not show any evidence of structural recurrence, the focus should be on monitoring the thyroglobulin levels and adjusting the treatment plan accordingly. The patient's stimulated thyroglobulin levels have been rising slowly (from 7.1 to 9.4), and the unstimulated levels have also been increasing (from 1.5 to 4.8), which suggests a biochemical incomplete response, as indicated in the guidelines from the Journal of the National Comprehensive Cancer Network 1. The guidelines recommend periodic neck ultrasound and TSH-stimulated thyroglobulin measurement in patients with stimulated Tg 1-10 ng/mL, which is the case for this patient. Additionally, the guidelines suggest considering TSH-stimulated radioiodine imaging in patients with abnormal thyroglobulin levels, which may be beneficial in this case if the thyroglobulin levels continue to rise. However, the negative biopsies of the lymph nodes and the lack of evidence of structural recurrence on imaging studies suggest that the disease is still at a microscopic level, and therefore, a more conservative approach may be appropriate. It is essential to balance the need for vigilance with the indolent nature of most papillary thyroid cancers, especially since the patient has had stable disease for several years without evidence of structural recurrence. Some key points to consider in the management of this patient include:

• Continuing surveillance with thyroglobulin monitoring every 6 months and annual neck ultrasound
• Maintaining TSH suppression therapy with levothyroxine, aiming for a TSH level between 0.1-0.5 mIU/L
• Considering more comprehensive imaging, including repeat neck and chest CT, if thyroglobulin levels continue to rise significantly
• Possibly considering empiric radioactive iodine therapy with a higher dose (150-200 mCi) if no structural disease is identified and thyroglobulin levels continue to rise. Overall, the goal is to monitor the patient's disease closely while minimizing the risk of overtreatment and its associated side effects.

From the Research

Next Steps in Management

The patient has been diagnosed with multifocal bilateral papillary thyroid carcinoma and has undergone a total thyroidectomy. The patient's thyroglobulin levels have been persistently detectable but low, and the patient has undergone multiple whole-body scans and ultrasounds, which have shown no evidence of local recurrence or metastatic disease. However, the patient's stimulated thyroglobulin level has been increasing, and the patient has been referred to Dr. Goldner for a second opinion.

Diagnostic Imaging

• The patient underwent a CT scan of the neck and chest, which showed some nodules concerning for recurrence and some lymph nodes concerning for metastatic disease 2.
• The patient underwent EBUS, FNA biopsies of level 4R and 7 lymph nodes, which showed features consistent with granulomatous lymphadenitis, and no malignant cells were identified.
• The patient's ultrasound and PET scan results have been unremarkable, but the patient's thyroglobulin levels continue to be detectable.

Role of 18F-FDG PET/CT

• 18F-FDG PET/CT has been shown to be useful in detecting recurrent and/or metastatic diseases in DTC patients with thyroglobulin elevation and negative iodine scintigraphy 3, 4, 2, 5.
• The diagnostic performance of 18F-FDG PET/CT is high, with a pooled sensitivity and specificity of 0.86 and 0.84, respectively 5.
• Thyroglobulin levels and thyroglobulin doubling time independently predict a positive 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma 6.

Management Considerations

• The patient's persistently detectable thyroglobulin levels and increasing stimulated thyroglobulin level suggest the possibility of recurrent or metastatic disease.
• The patient's CT scan and biopsy results do not show definitive evidence of recurrence or metastasis, but the patient's thyroglobulin levels continue to be detectable.
• Further management considerations may include:
  • Continued surveillance with ultrasound and thyroglobulin levels
  • Consideration of additional diagnostic imaging, such as 18F-FDG PET/CT
  • Discussion of potential treatment options, such as additional surgery or radioactive iodine therapy, if recurrence or metastasis is confirmed.