Evaluation and treatment of persistent thyroglobulinemia in patients with well-differentiated thyroid cancer

Abstract

Whereas in the past a negative diagnostic 131 I whole body scan (WBS) was interpreted as the lack of significant residual or recurrent thyroid cancer, today the patient with negative WBS and measurable serum thyroglobulin (Tg) presents a diagnostic and therapeutic dilemma. Previous studies have shown a high rate of visualization of uptake and a decrease in Tg after one or more therapeutic doses of 131 I. In order to further assess the significance of this finding, retrospective analysis of patients with persistent thyroglobulinemia and negative WBS was performed for evidence of surgically amenable disease. Seven out of seventeen patients had neck ultrasound and/or computerized tomography (neck Ϯ chest) showing the presence of pathologically confirmed malignant masses ranging from 1 to 4 cm in size. Their serum Tg while on L-thyroxine ranged between 2.4 and 1173 pmol/l. Removal of the identified masses resulted in a greater than 75% reduction in serum Tg in four out of five patients in the group. One patient achieved a serum Tg of < 1.5 pmol/l while hypothyroid. Empiric 131 I treatment of eleven patients with persistent thyroglobulinemia resulted in demonstrated uptake on post-therapy scan in seven. Further study is needed to compare the efficacy, safety and cost of a diagnostic approach to radiologically identify and surgically resect identified disease versus empiric therapeutic 131 I treatment and high-dose WBS in this group of patients. Patients with negative WBS and persistent thyroglobulinemia, even to levels < 4.5 pmol/l, may have significant foci of thyroid cancer in surgically accessible areas. This suggests the need for a redefinition or clarification of the term 'recurrence' in thyroid cancer.

Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin

“…We have shown previously that the diet described results in low iodine excretion (22). The findings of several studies support the use of blind treatment with high-dose 131 I in cases of negative diagnostic scanning and increased serum Tg, because a post-treatment decline in serum Tg was observed (Table 6) (6,13,15,23,24). Most studies describe the treatment results only in patients with a positive post-treatment WBS, but the number of patients and follow-up data in these studies were limited (Table 6).…”

Practice Trends in Patients with Persistent Detectable Thyroglobulin and Negative Diagnostic Radioiodine Whole Body Scans: A Survey of American Thyroid Association Members

“…Subsequent reports demonstrated that more than half of such patients, if given an empiric therapeutic dose of 131 I, had visible uptake on a post-therapy WBS, and the median percentage of positive scans was 57% (range 0-94%) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Most lesions were in the cervical lymph nodes, but thyroid bed uptake (which could represent normal thyroid remnant) and distant metastases were also detected.…”

“…In the late 1980s to mid-1990s, several authors reported that if given a therapeutic dose of 131 I, 64-94% of patients with positive serum Tg but negative DxWBS (Tg + /WBS -) would have detectable residual thyroid cancer in a post-therapy 131 I scan (2)(3)(4)(5). Numerous subsequent reports confirmed these early results, and the median percentage of positive post-therapy 131 I-WBS was 57% (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). While many advocated the use of an empiric dose of 131 I, others cautioned against its routine use, given the side effects and unproven benefits (10,(17)(18)(19)(20).…”

Evaluation of the First Automated Thyroglobulin Assay

“…As detectable serum Tg usually results in further imaging work-up or even therapy (6,7), this lowest concentration range is of far greater clinical significance for Tg assays than for most other tumor markers; therefore our evaluation was planned to focus particularly on the assay imprecision at the lowest concentration range.…”