Long-term course and predictive factors of elevated serum thyroglobulin and negative diagnostic radioiodine whole body scan in differentiated thyroid cancer

J Endocrinol Invest. 2005 Jun;28(6):540-6. doi: 10.1007/BF03347243.


Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and negative diagnostic radioactive iodine (RAI) whole body scan (DxWBS). The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to determine the predictive factors for the development of high Tg and negative DxWBS (Tg+/scan-) and to study the long-term course of the disease in patients with this condition.

Methods: We, retrospectively, reviewed the medical records of a cohort of 105 non-selected DTC patients (26 males and 79 females; median age 37.7 yr, range 7-72). None of these patients had positive Tg antibodies or distant metastases. All Tg levels were obtained off thyroid hormone therapy. At the first follow-up visit after RAI ablation (13 +/- 7.6 months), patients were classified into those with low Tg (<2 ng/ml off L-T4) and negative DxWBS (control group) and those with high Tg ( > or = 22 ng/ ml off L-T4) and negative DxWBS (Tg+/scan- group). Using univariate and multivariate logistic regression analyses, we evaluated a number of parameters (see results) for their association with the development of Tg+/scan-. In addition, the long-term course of the disease in Tg+/scan- group was analyzed.

Results: In univariate analysis, the following factors were found to be significantly associated with Tg+/scan-: perithyroidal tumor extension (p=0.025), soft tissue invasion (p=0.001), cervical lymph node metastases (p=0.014) and Tg level before RAI ablation (p=0.015). In multivariate analysis, only soft tissue invasion remained significantly associated with Tg+/scan- [p 0.001, odds ratio, 15.6 (95% Cl, 2.96-82.06)]. Age, sex, duration of goiter before surgery, pressure symptoms, tumor size, tumor multifocality, lymph nodedissection at initial surgery, tumor-node-metastasis (TNM) stage, and RAI ablative dose were not associated with Tg+/ scan-. In 53 patients with Tg+/scan-, 42 cases were followed without any therapeutic intervention; over a median follow-up of 71.6 months (range, 13-144.7), 31 cases had a spontaneous remission and 11 cases continued to have a persistent disease (Tg > or = 2 ng/ml, negative DxWBS, and no palpable disease or distant metastases); Tg declined from 9.32 +/- 9.91 ng/ml at first visit after RAI ablation to 1.59 +/- 5.39 ng/ml at last visit (p<0.0001). In the other 11 cases of Tg+/scan- group, one or more therapeutic interventions (RAI, surgery, or external radiotherapy) were undertaken. Over a median follow-up of 98.4 months (range, 6-147), Tg decreased from 110.2 +/- 147.5 to 23.5 +/- 41.2 ng/ml (p 0.026); 4 cases achieved remission, 5 cases continued to have persistent disease, and 2 cases had progression of their disease, which led to their death.

Conclusion: Soft tissue invasion on original surgery strongly predicts the development of Tg+/scan- in DTC patients. The long-term course of the disease is mostly favorable especially when the Tg level is only modestly elevated.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Child
  • Female
  • Humans
  • Iodine Radioisotopes* / therapeutic use
  • Logistic Models
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neck
  • Neoplasm Invasiveness
  • Prognosis
  • Radionuclide Imaging
  • Remission Induction
  • Retrospective Studies
  • Survival Rate
  • Thyroglobulin / blood*
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / diagnostic imaging*
  • Thyroid Neoplasms / radiotherapy


  • Iodine Radioisotopes
  • Thyroglobulin