(Second of Two Parts) Circulating Thyroglobulin For several decades, thyroglobulin was thought to be confined to the thyroid gland. This view can no longer be defended since thyroglobulin has unque...

Control of Thyroglobulin Synthesis and Secretion

Serum thyroglobulin (Tg) measurements in patients with treated differentiated thyroid cancer are usually well correlated with the presence or absence of residual or metastatic thyroid tissue. However, it is not rare to find a patient with detectable serum Tg levels but negative 131I whole-body scan (WBS) and no evidence of disease activity. To clarify the reason for this discrepancy, we decided to perform the WBS after the administration of a therapeutic dose of 131I in 17 consecutive patients in whom serum Tg was detectable while the WBS performed with a 5 mCi tracer dose was negative (12.6% of 135 patients studied with both WBS and serum Tg). The result of this study demonstrated that after this procedure the WBS became positive for significant residual or metastatic areas of radioiodine uptake in all patients but one. Such data indicate that in our patients the presence of circulating Tg is not a false-positive Tg result, but is due to the presence of residual or metastatic tissue that is not detected in the conventional WBS, that can be visualized using therapeutic doses. Preliminary follow-up data indicate that this procedure may also have therapeutic effect, although the relevance of this aspect remains to be established.

Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels.

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

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (> or = 1:10) as assessed by passive hemagglutination were discarded. Assays were carried out under conditions in which anti-Tg titers less than 1:10 produced no interference. The assay sensitivity was 1.25 ng/ml and the mean +/- SE concentration of serum hTg in 58 control subjects was 9.5 +/- 0.9 ng/ml (range < 1.25-27 ng/ml). A slight but significant (p < 0.025) increase in the mean hTg level was observed in 12 pregnant women at delivery (25.7 +/- 5.2 ng/ml). Moderate to marked elevations of serum hTg were observed in patients with nontoxic goiter (61.4 +/- 15 ng/ml; n = 23), subacute thyroiditis (138 +/- 67 ng/ml; n = 5), toxic adenoma (129 +/- 47 ng/ml; n = 13), untreated (424 +/- 101 ng/ml; n = 35) or treated (328 +/- 222 ng/ml; n = 14) toxic diffuse goiter. 88 patients with thyroid carcinoma and 10 with nonthyroidal malignancies were studied. The mean level of serum hTg was increased in untreated differentiated thyroid carcinoma (89.5 +/- 19 ng/ml; n = 13) but not in undifferentiated (10 +/- 2.9 ng/ml; n = 6) or medullary (0.8 +/- 0.2 ng/ml; = 3) carcinoma. In treated differentiated thyroid carcinoma the mean hTg levels were normal (8.2 +/- 0.2 ng/ml) in patients (n = 24) with no evidence of either a thyroid residue or metastatic disease, moderately increased (56.6 +/- 16 ng/ml) in patients (n = 27) with residual thyroid tissue, markedly elevated in patients with lymph node metastases (199 +/- 50 ng/ml; n = 5) and extremely elevated in those with bone (4004 +/- 982 ng/ml; n = 8) or lung (2520 +/- 620 ng/ml; n = 5) metastases. There was no significant difference in serum hTg between functioning (n = 23) and nonfunctioning (n = 5) metastases as assessed by 131I whole body scan. A slight but significant (p < 0.0005) increase in the mean concentration of hTg was observed in nonthyroidal malignancies (21.7 +/- 4.5 ng/ml; n = 10). Serial measurements showed a transient increase of serum hTg after 131I therapy of differentiated thyroid carcinoma, toxic diffuse goiter or toxic adenoma, with peak values usually occurring within the first three days. A fall of serum hTg after administration of suppressive doses of thyroid hormone to patients with nontoxic goiter and a rise after discontinuation of thyroid suppressive therapy in patients with metastatic differentiated thyroid carcinoma was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum thyroglobulin in thyroid carcinoma and other thyroid disorders

Serum thyroglobulin (Tg) was measured by radioimmunoassay in sixty-two control subjects, 163 euthyroid patients with nodular goitre and eighty-one patients with previously treated differentiated thyroid carcinoma. Tg was elevated in 65% of nodular goitres and failed to fall with thyroxine treatment in ten/fifteen patients treated. A diagnosis of differentiated carcinoma was confirmed in fourteen/sixty-four of these patients and Tg was elevated in twelve. Of sixty-five treated thyroid carcinoma patients without evidence of residual tumour, serum Tg was undetectable in thirty-nine, normal in twenty-four and elevated in two. There was evidence of residual tissue in the thyroid in seventeen of the patients with detectable Tg. Of the sixteen patients with residual tumour or metastases Tg was elevated in fifteen. There was a positive correlation between goitre size and Tg levels in multinodular goitre, and thyroid carcinomas of large bulk were associated with higher Tg levels. Serum Tg was normal in medullary carcinoma and in two patients with thyroid metastases from extra-thyroidal malignancies. High Tg levels in patients with residual metastases from thyroid carcinoma following thyroid ablation indicates Tg production by tumour tissue. Measurement of serum Tg of limited value in the differential diagnosis of nodular thyroid disease. It is particularly useful following surgery and 131I therapy for differentiated thyroid carcinoma. In these patients it gives confirmation of thyroid albation and may provide evidence of residual tumour tissue when the other tests are negative.

Serum thyroglobulin in the diagnosis and management of thyroid carcinoma.

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Serum thyroglobulin in the diagnosis and management of thyroid carcinoma.