Does undetectable basal Tg measured with a highly sensitive assay in the absence of antibodies and combined with normal ultrasonography ensure the absence of disease in patients treated for thyroid carcinoma?

Abstract

False-negative result of highly sensitive thyroglobulin INTRODUCTION M easurement of serum thyroglobulin (Tg) is considered to be the most sensitive method for the detection of persistent or recurrent disease in patients with differentiated thyroid carcinoma after initial therapy. Obviously, the sensitivity of this marker is limited in patients with poorly differentiated tumors that do not secrete Tg, or in patients with circulating anti-thyroglobulin antibodies (TgAb) that interfere with serum Tg measurement (false reduction). In addition, positive serum Tg result depends on the secretion of sufficient amounts, which can be detected by the assay. The use of highly sensitive assays enables the detection of even minimal amounts of Tg in the circulation, which would not be identified by traditional assays. The exceptional cases of persistent/recurrent disease, in which basal (no TSH stimulation) Tg levels may be undetectable with these assays, would be due to small cervical lymph node metastases or local recurrence (1-7), which could be identified by ultrasonography (US). Therefore, the observation of undetectable basal Tg levels measured by highly sensitive assays in patients with well-differentiated tumors, in the absence of circulating TgAb and combined with negative US, ensures the absence of disea se at that time, and as along as the results continue the same (1,2,4-6,8). We report here a series of five patients who exhibited tumor persistence or recurrence despite the presence of this combination of findings. CASE REPORTAll patients had well-differentiated thyroid carcinoma (papillary type) and had undergone total thyroidectomy with apparently complete tumor resection, followed by remnant ablation with 131I (3.7-5.5 GBq). Initial post-therapy whole-body scanning (RxWBS) revealed no distant metastases. When tumor persistence or recurrence was detected, all patients presented undetectable basal Tg (0.1 ng/ml) in the absence of TgAb, and US showed no anomalies. The characteristics of each patient are shown in Table 1.Tg was measured with a highly sensitive chemiluminescent assay (Tg Access, Beckman Coulter, Fullerton, CA), with functional sensitivity of 0.1 ng/mL. This assay had been used in recent series (1,2,4,5,7). TgAb were determined by a chemiluminescent assay (Immulite 2000), with a detection limit of 20 IU/mL, and reference value of up to 40 IU/mL.Ultrasonography was performed with a linear multifrequency 10-MHz transducer. RxWBS was performed with a therapeutic dose of 131I (3.7-5.5 GBq), after stimulation with recombinant human TSH (rhTSH) and administration of a low-iodine diet for the 10 days before the examination. Anterior and posterior whole--body images were obtained 7 days after iodine administration. FDG-PET was also carried out after stimulation with rhTSH. Computed tomography (CT) was performed on 5-10 mm sequential sections. DISCUSSIONSeveral studies have evaluated the performance of highly sensitive Tg assays in patients treated for differentiated thyroid carcinoma without circulating TgAb...

Papillary Thyroid Carcinoma Recurrence: Low Yield of Neck Ultrasound With an Undetectable Serum Thyroglobulin Level

“…One study found that 3 of 250 patients (1.2%) had recurrence with an undetectable serum Tg level after recombinant human thyrotropin stimulation but used a substantially less‐sensitive serum Tg assay with a discriminatory value of 1 ng/mL . The second was a case series of 5 patients with recurrence and undetectable serum Tg levels, but only 3 of the recurrences were in the neck, and none were identified by neck US . In the third study, surveillance neck US found recurrence in only 1 of 170 patients without biochemical signs of recurrence .…”

“…Many patients then undergo serial neck ultrasound (US) examinations (imaging of the thyroid and lateral neck) with serum thyroglobulin (Tg) measurement to monitor for local recurrence. Serum Tg is a highly sensitive biomarker for recurrent disease in patients with differentiated PTC . However, it cannot be used as an effective marker when anti‐Tg antibodies are present, as the anti‐Tg antibodies can lead to falsely low serum Tg measurements …”

“…Serum Tg is a highly sensitive biomarker for recurrent disease in patients with differentiated PTC. [5][6][7][8] However, it cannot be used as an effective marker when anti-Tg antibodies are present, as the anti-Tg antibodies can lead to falsely low serum Tg measurements. 2,8,9 Five percent to 20% of patients with differentiated thyroid cancer have local or regional recurrences, which in most cases are located within the neck.…”

“…[5][6][7][8] However, it cannot be used as an effective marker when anti-Tg antibodies are present, as the anti-Tg antibodies can lead to falsely low serum Tg measurements. 2,8,9 Five percent to 20% of patients with differentiated thyroid cancer have local or regional recurrences, which in most cases are located within the neck. [10][11][12] The goal of postsurgical follow-up in these patients is the early discovery of persistent or recurrent disease.…”

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus

“…Ultrasensitive Tg tests (functional sensitivity ≤ 0.2 ng/ml) are available in Brazil and may reduce the need to measure stimulated Tg (141). Indeed, when Tg is measured using these tests, stimulation becomes unnecessary in low-risk patients with undetectable Tg [T4] levels, no TgAc interference, and negative US findings (141)(142)(143)(144)(145). Diagnostic WBS concomitant with stimulated Tg may be helpful in intermediate-or high-risk patients (140); however, its value has not been established (138).…”