Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: Including comments on the role of serum thyroglobulin monitoring in tumor surveillance

https://doi.org/10.1053/nm.2000.4600Get rights and content

Differentiated thyroid cancer (DTC) patients, especially the 10% to 15% at high risk of cancer-related death, should have long-term monitoring for detection of recurrence or metastasis. Conventional radiologic and ultrasonographic imaging is useful for localization of recurrent or persistent disease. For patients who have had ablation of residual thyroid tissue, measurement of serum thyroglobulin (Tg) levels and radioactive iodine (RAI) imaging provide highly sensitive tools for early detection. Serum Tg is reliable only in the absence of Tg autoantibodies. Sensitivity increases with TSH stimulation, either by withdrawal of thyroxine (T4) therapy, or administration of recombinant TSH (rTSH). In some patients, serum Tg levels are positive but the RAI whole body scan (WBS) is negative. In these patients, either the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between Tg synthesis and the iodine-trapping mechanism. Recent literature suggests that empiric high-dose RAI therapy of Tgpositive diagnostic scan-negative patients may result in a high rate of visualization of uptake in posttherapy scans (PTS). Evidence for subsequent improvement of parameters of disease activity has also been presented. Almost all such reported cases had micrometastases that were not visualized by conventional imaging. In our experience, aggressive macrometastases with negative diagnostic WBS do not show significant uptake after therapeutic doses of RAI. The small size of micrometastases in the first group of patients and a possible defect of the iodine-trapping mechanism in the second group may explain this apparent discrepancy. Based on presently available information, a generalized recommendation for RAI therapy of Tg-positive, diagnostic scan-negative patients should await further studies. Meanwhile, in some high-risk patients, in the absence of alternative therapies, empiric RAI therapy is justified.

References (66)

  • SchlumbergerMJ

    Papillary and follicular thyroid carcinoma

    N Engl J Med

    (1998)
  • HayID et al.

    Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989

    Surgery

    (1993)
  • GrebeSK et al.

    Follicular cell-derived thyroid carcinomas

    Cancer Treat Res

    (1997)
  • Van HerleAJ et al.

    Control of thyroglobulin synthesis and secretion

    N Engl J Med

    (1979)
  • HayID et al.

    AACE clinical practice guidelines for the management of thyroid carcinoma

    Endocrine Practice

    (1997)
  • MazzaferriEL et al.

    Papillary thyroid carcinoma: the impact of therapy in 576 patients

    Medicine

    (1977)
  • MazzaferriEL

    Thyroid remnant 131I ablation for papillary and follicular thyroid carcinoma

    Thyroid

    (1997)
  • MazzaferriEL et al.

    Differentiated thyroid cancer: long-term impact of initial therapy

    Trans Am Clin Climatol Assoc

    (1994)
  • LinJD et al.

    The effects of radioactive iodine in thyroid remnant ablation and treatment of well differentiated thyroid carcinoma

    Br J Radiol

    (1998)
  • SchlumbergerM et al.

    131I therapy for elevated thyroglobulin levels

    Thyroid

    (1997)
  • BrendelAJ et al.

    Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma

    Eur J Nucl Med

    (1990)
  • PaciniF et al.

    Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels

    J Nucl Med

    (1987)
  • PinedaJD et al.

    Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan

    J Clin Endocrinol Metab

    (1995)
  • Van HerleAJ et al.

    Radioimmunoassay for measurement of thyroglobulin in human serum

    J Clin Invest

    (1973)
  • SchaadtB et al.

    Assessment of the influence of thyroglobulin (Tg) autoantibodies and other interfering factors on the use of serum Tg as tumor marker in differentiated thyroid carcinoma

    Thyroid

    (1995)
  • PreissnerCM et al.

    Nonisotopic “sandwich” immunoassay of thyroglobulin in serum by the biotinstreptavidin technique: evaluation and comparison with an immunoradiometric assay

    Clin Chem

    (1988)
  • SchlumbergerM et al.

    A new immunoradiometric assay (IRMA) system for thyroglobulin measurement in the follow-up of thyroid cancer patients

    Eur J Nucl Med

    (1991)
  • Feldt-RasmussenU et al.

    Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity

    Ann Biol Clin (Paris)

    (1996)
  • SpencerCA et al.

    Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma

    J Clin Endocrinol Metab

    (1998)
  • SchlumbergerM et al.

    Serum thyroglobulin determination in the follow-up of patients with differentiated thyroid carcinoma

    Eur J Endocrinol

    (1998)
  • Van WyngaardenK et al.

    Is serum thyroglobulin a useful marker for thyroid cancer in patients who have not had ablation of residual thyroid tissue?

    Thyroid

    (1997)
  • WartofskyL et al.

    The use of radioactive iodine in patients with papillary and follicular thyroid cancer

    J Clin Endocrinol Metab

    (1998)
  • OzataM et al.

    Serum thyroglobulin in the follow-up of patients with treated differentiated thyroid cancer

    J Clin Endocrinol Metab

    (1994)

    • Cited by (62)

    • Low correlation between serum thyroglobulin and <sup>131</sup>I radioiodine whole body scintigraphy: implication for postoperative disease surveillance in differentiated thyroid cancer

      2022, Clinical Imaging
      Citation Excerpt :

      Patient selection for postoperative RAI ablation therapy is based on clinical and histopathologic risk stratification. Empiric RAI treatment of Tg positive, PA-WBS negative patients remains controversial.21–23 Proponents of this approach contend that small tumor size or micrometastasis maybe below the detection sensitivity of diagnostic RAI whole-body scintigraphy.

    • Simultaneous measurements of single gamma ray of <sup>131</sup>I and annihilation radiation of <sup>18</sup>F with Compton PET hybrid camera

      2021, Applied Radiation and Isotopes
      Citation Excerpt :

      On the contrary, when no accumulation is observed in the anterior neck, 131I scintigraphy alone is insufficient to determine whether treatment should be continued. This can be attributed to the refractoriness to internal 131I therapy (Fatourechi and Hay, 2000) (Frilling et al., 2000). Although 131I is more likely to accumulate in normal thyroid tissues and well-differentiated thyroid cancer tissues, it is less likely to accumulate in poorly differentiated to undifferentiated thyroid cancer tissues.

    • Head-to-head comparison of F-18 FDG PET/CT in radioidine refractory thyroid cancer patients with elevated versus suppressed TSH levels a pilot study

      2020, Heliyon

    • Postoperative Management of Thyroid Carcinoma

      2008, Surgical Oncology Clinics of North America
      Citation Excerpt :

      In patients who have non–iodine-avid DTC recurrence demonstrated by elevated Tg alone and a negative WBS, some authors advocate empiric 131I therapy on the theory that micrometastases too small to be detected by low-dose WBS may still take up some iodine (such lesions are sometimes seen on posttherapy scans) [46,47]. This strategy is controversial, however, and its efficacy has been questioned [48–50]. The most common sites of distant metastases from DTC are the lungs, bone, and central nervous system.

    • Incremental diagnostic value of SPECT/CT to post-radioiodine therapy planar whole-body scan in patients with papillary thyroid cancer

      2023, Research Square

    • [<sup>68</sup>Ga]Ga-DOTATATE PET/CT Versus [<sup>18</sup>F]F-FDG PET/CT in Tenis Syndrome - a Head-to-head Comparison With Elevated and Suppressed Tsh Levels in Papillary Thyroid Carcinoma – a Pilot Study

      2023, Research Square
    View all citing articles on Scopus
    View full text
    Copyright © 2000 Published by Elsevier Inc.