Post total thyroidectomy elevated anti-thyroglobulin antibodies in patients with differentiated thyroid cancer - Residual disease or residual thyroiditis?

Objectives: Elevated serum thyroglobulin (S.Tg) with negative anti-thyroglobulin antibody titre or a rising serum anti-thyroglobulin (S.ATg) titre is known to indicate biochemical disease in patients with differentiated thyroid cancer (DTC), post-surgery. However, histopathologic examination of the surgical specimen often shows foci of lymphocytic thyroiditis synchronous with the primary DTC. Whether this has implications on the serum titres of S. Tg and S. ATg merits further exploration. The present study was conducted to correlate baseline elevated S. ATg in patients of DTC with histopathology of total thyroidectomy specimen showing features of thyroiditis and if any statistically significant difference existed in comparison to those with non- thyroiditis histology.

Methods: Records of 432 patients with DTC post total/ completion thyroidectomy were retrospectively reviewed. Patients with documented pre-¹³¹I treatment S. Tg and S. ATg values were included in the study. A total of 267 candidates were included and grouped into thyroiditis positive and thyroiditis negative groups based up on the presence of lymphomononuclear inflammatory infiltration in histopathology of the thyroidectomy specimen. Patients were considered positive for thyroiditis if there was moderate to severe lymphomononuclear infiltrate in the background of thyroid carcinoma and negative in absence of the same.

Results: 95 patients (70 women, 25 men; mean age 42.9±24.8 years) with findings of thyroiditis on histopathology had a median S. ATg of 97.8 IU/ml (IQR- 246.2) whereas 172 patients (118 women, 54 men; mean age 41.9±29.8 years) with no thyroiditis on histopathology had a median S. ATg of 16.7 IU/ml (IQR- 15.48), with this difference being statistically significant (p<0.001). 69/95 candidates with thyroiditis and 24/172 candidates without thyroiditis had positive S. ATg. All patients in thyroiditis group had papillary thyroid cancer on histopathology, while 132 patients in the non-thyroiditis group had papillary carcinoma, 22 had papillary variant of follicular carcinoma and 18 had follicular carcinoma. Elevated S. ATg had a significant positive correlation (correlation coefficient- 0.59, p value <0.001) with presence of thyroiditis on Spearman’s test. However, there was no significant difference between the age distribution among the groups, cumulative ¹³¹I dose or time taken for the patients to become scan negative after receiving radioiodine therapy (p >0.05).

Conclusions: The study demonstrates a statistically significant positive correlation of elevated pre- ¹³¹I-treatment thyroglobulin antibodies with the presence of synchronous lymphocytic thyroiditis in the background of differentiated thyroid carcinoma on histopathology. The higher levels of S. ATg interferes with usual assays for measurement of thyroglobulin levels and can falsely indicate presence of residual disease. Hence, routine baseline (pre- ¹³¹I-treatment) measurement of S. Tg and S. ATg and their correlation with the histopathology findings can help in identification of the etiology behind the raised values in the subgroup of patients having co-existent thyroiditis with DTC.