The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.

/pdf/serum-thyroglobulin-autoantibodies-prevalence-influence-on-yhz00gbdsc.pdf

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

Objective: Serum thyroglobulin (Tg) is the marker of differentiated thyroid carcinoma (DTC) after total thyroidectomy, but its value is limited by the interference of anti-Tg antibodies (TgAb). Detection of Tg in fine-needle aspiration biopsy (Tg-FNAB) washout fluid is used to identify neck DTC recurrences/metastases, but the interference of serum TgAb in this procedure is unknown. Patients and Methods: Seventy-three patients (41 after surgery for thyroid cancer and 32 with thyroid nodules) evaluated for suspicious cervical lymph nodes were retrospectively reviewed. Tg was assayed by immunoradiometric assay or chemiluminescent assay in ultrasound-guided FNAB used for cytology. Serum TgAb were detected by passive agglutination or chemiluminescent assay. On the basis of preliminary data obtained in lymphadenitis, Tg-FNAB more than 36 ng/ml and more than 1.7 ng/ml (in the presence or absence of thyroid gland, respectively) was considered as indicative of metastasis. Results: In 51 TgAb-negative patients, Tg-...

/pdf/the-diagnostic-value-for-differentiated-thyroid-carcinoma-2lhff42360.pdf

The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-tg antibodies

Objectives: The aim of the study was to evaluate the usefulness of the antithyroglobulin autoantibody (TgAb) value at 6–12 months after remnant ablation in predicting recurrence in differentiated thyroid carcinoma patients who had undetectable thyroglobulin (Tg) values. The change in TgAb concentration measured between the time of remnant ablation (TgAb1) and 6–12 months thereafter (TgAb2) was also evaluated as a possible prognostic indicator. Patients and Methods: Patients with differentiated thyroid carcinoma who underwent total thyroidectomy followed by 131I remnant ablation between 1995 and 2003 at the Asan Medical Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg at 6–12 months after remnant ablation during thyroid hormone withdrawal were the subjects of this study. Results: TgAb2 was positive in 56 patients. Ten of 56 patients (18%) with positive TgAb2 had recurrence, whereas only 10 of 768 patients (1%) with negative TgAb2 had recurrence during 73.6 months of follow-u...

/pdf/change-of-serum-antithyroglobulin-antibody-levels-is-useful-dgb5bj1xde.pdf

Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma.

Summary
objective To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow-up of patients with differentiated thyroid carcinoma.

design and methods  We conducted a meta-analysis of the literature from 1975 to 2003 on serum Tg measurements in the follow-up of differentiated thyroid carcinoma. In a computer-based search, we initially found 915 articles that were finally narrowed down to 120. These 120 papers were subjected to strict in/and exclusion criteria, leaving 46 articles (totalling 9094 patients). Data from these articles were extracted in a structured fashion and were grouped according to initial therapy, TSH status, Tg assay method and definition of a ‘gold standard’. Original 2 × 2 tables were pooled by summary receiver operating characteristic curve analysis (sROCa), best estimates of sensitivity and specificity being obtained by the combination of sROCa and Mantel–Haenszel odds ratios.

results  Despite considerable differences between series in laboratory and clinical methodology, we consistently found higher specificity for Tg measurements after thyroid remnant ablation than after surgery alone. Highest pooled sensitivity 0·961 ± 0·013 (SE) was found for immunometric assay (IMA) after thyroid remnant ablation and thyroid hormone withdrawal, at a specificity of 0·947 ± 0·007. Pooled sensitivity decreased significantly if ablated patients were tested while on thyroid hormone (0·778 ± 0·023, at a specificity of 0·977 ± 0·005). Significantly decreased pooled specificity was found in patients who did not undergo remnant ablation (sensitivity 0·972 ± 0·023, at a specificity of 0·759 ± 0·028). If recombinant human TSH (rhTSH) stimulation was used as a substitute for thyroxine withdrawal, sensitivity remained high (0·925 ± 0·018) while specificity decreased to 0·880 ± 0·013. In all analyses, specificity of Tg would decrease when unspecified activity in the thyroid region at scintigraphy was considered benign, whereas sensitivity decreased when such activity was considered malignant.

conclusion  This study confirms that the best accuracy of Tg-guided follow-up in patients treated for differentiated thyroid carcinoma is obtained if treatment includes remnant ablation, and Tg testing is performed while off thyroxine.

Diagnostic value of serum thyroglobulin measurements in the follow-up of differentiated thyroid carcinoma, a structured meta-analysis

Summary
objective This study was designed to investigate whether an elevated serum antithyroglobulin antibody (TgAb) reflects cancer recurrence in thyroglobulin (Tg)-undetectable patients with differentiated thyroid carcinoma (DTC) after thyroid ablation.

design We measured serum TgAb level and evaluated the disease status in 226 DTC patients who had undergone remnant ablation and showed an undetectable Tg result as assessed by immunoradiometric assay.

measurements Radioligand assay of TgAb was performed. Recurrence was assessed by 131I scan, 18F-fluorodeoxyglucose positron emission tomography, sonography, computed tomography, or by surgical operation.

results Fifty-one patients (22·6%) of the Tg-undetectable patients showed positive TgAb, and 25 (49·0%) of these were confirmed with recurrence. The recurrence rate of TgAb-positive patients was higher than that of TgAb-negative patients (3·4%; P < 0·0001). During follow-up, 73·1% of the disease-free patients showed spontaneously decreased TgAb levels. A total of 71·4% of patients with recurrent cancer, who showed responses to surgical operation or radio-iodine treatment, also showed a decreased TgAb level.

conclusions Persistently elevated TgAb levels appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum Tg results. Thus, the routine measurement of TgAb in such patient populations may be indicated.

Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation

A total of 1050 patients with differentiated thyroid cancer (DTC) have been followed in the Thyroid Center of Padua by means of serum thyroglobulin (Tg) measured with IRMA method and anti-Tg antibodies (TgAb) assays. Circulating TgAbs were detected in 102 (9.7%) patients. In 32 of these 102, TgAbs were evaluated before and after total thyroidectomy and 131I ablation. In these patients no relationship was found between preoperative serum TgAb levels on the one hand and tumor stage at diagnosis or outcome of the disease on the other. During the follow-up, TgAb serum levels decreased or disappeared in 21 cases considered tumor-free, while they remained unchanged or even increased, in comparison with the preoperative ones, in 11 patients, 5 with proven metastases and 6 considered tumor-free. Evaluating the whole group of 102 TgAb-positive patients, we observed that TgAb serum levels, measured after thyroid ablation, were significantly higher in cases with metastases than in those considered tumor-free (653.0 +/- 196.9 vs 157.7 +/- 116.5 U/ml, m +/- SD, p less than 0.0001). In the group of patients with metastases and circulating TgAbs, Tg serum levels were elevated in 27% of cases on TSH-suppressive therapy and in 44% off therapy when nodal metastases were present, and in 67% of cases on TSH-suppressive therapy and in 83% off therapy when distant metastases were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of the combined antithyroglobulin antibodies and thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer

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Usefulness of the combined antithyroglobulin antibodies and thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer