Incidence and implications of negative serum thyroglobulin but positive I‐131 whole‐body scans in patients with well‐differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal

Abstract

Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal.

Possible delayed diagnosis and treatment of metastatic differentiated thyroid cancer by adopting the 2015 ATA guidelines

“…Serum thyroglobulin determination has an important role in post-operative risk stratification, but post-operative Tg levels alone cannot be used as a milestone criterion to recommend for or against I-131. New recommendations include using post-operative Tg measurement (a few weeks after total thyroidectomy either TSH stimulated or not stimulated) as a tool to discriminate between high and low-risk patients and consequently for indication to adjuvant I-131 (35). Moreover, in some cases, Tg can be false negative in recurrent or metastatic DTC patients when there are thyroglobulin antibodies present (36).…”

“…As underlined in ATA 2015 guidelines (4), no precise Tg value cutoffs are established to define what is a complete thyroid removal to omit RAIT. Postoperative Tg value is strongly dependent on the type of determination (stimulated or nonstimulated), type of stimulation (rh-TSH vs withdrawal), the actual level of TSH stimulation and the volume of remnant thyroid tissue (9,35,36). In our study, 25% of patients without pre-surgery known metastases had low stimulated Tg values (less than 10 ng/mL), not suggesting the presence of distant metastases, confirming the poor value of post-operative Tg alone in the decision making for I-131.…”

Radioiodine treatment after surgery for differentiated thyroid cancer: a reasonable option

“…Indeed, postoperative serum Tg value is strongly dependent on the type of determination (stimulated or nonstimulated), type of stimulation (rh-TSH vs. endogenous hypothyroid stimulation), the actual level of TSH stimulation and the volume of remnant thyroid tissue. Therefore, the level of postoperative Tg cannot alone guide the decision for or against RAI administration [29,30,34]. It appears that the postoperative serum Tg value will be more helpful in identifying patients that will benefit from RAI ablation rather than in identifying patients that do not require ablation [4].…”

“…New recommendations include using postsurgical Tg measurement (either TSH stimulated or nonstimulated, obtained a few weeks after total thyroidectomy and before RAI remnant ablation) as a tool to aid in initial risk stratification and adjuvant RAI therapy decision-making [4]. However, a post-treatment RAI whole body scan (post-Rx WBS) demonstrating residual thyroid tissue with a corresponding undetectable serum Tg was reported in up to 20% of DTC patients [29]. Moreover, up to 6% of such patients had confirmed loco-regional or distant metastases in addition to thyroid tissue remnants [30].…”

Biochemical Testing in Thyroid Disorders

“…Serum Tg measurements obtained during thyroid hormone suppression should be interpreted cautiously because they may fail to identify patients with small amounts of residual disease. 84–87 A neck ultrasound examination is thus invaluable to identify possible residual cancer even when serum Tg is undetectable. 88–90 Additionally, even TSH-stimulated Tg measurement may fail to identify patients with clinically significant thyroid cancer because of either anti-Tg antibodies (which should always be quantitatively assessed with every measurement of serum Tg) or because of decreased or absent production and secretion of immunoreactive Tg by tumor cells, as seen in poorly differentiated thyroid cancers.…”