title: Significance of Low Levels of Thyroglobulin Autoantibodies Associated with Undetectable Thyroglobulin After Thyroidectomy for Differentiated Thyroid Carcinoma.
abstract: The management of patients with differentiated thyroid carcinoma (DTC) showing low levels of serum thyroglobulin autoantibodies (TgAb) and undetectable Tg after thyroidectomy is unsettled. This study sought to elucidate the clinical significance of low levels of TgAb and to evaluate their interference with Tg measurement in vitro.
  
  
  
  Tg and TgAb levels were correlated with the post-thyroidectomy staging of 177 consecutive DTC patients undergoing (131)I ablation after total thyroidectomy (clinical study). Tg was measured by an immunometric assay (functional sensitivity: 0.1 ng/mL), and TgAb were evaluated by six assays (functional sensitivities: 1.2-96 IU/mL; positive cutoffs: 4-150 IU/mL). The changes in Tg concentration (Tg recovery) of diluted specimens from DTC patients were also measured after incubation with 67 sera from DTC patients with undetectable Tg and low levels of TgAb (in vitro study). DTC sera containing Tg were diluted serially (from 330 to 0.1 ng/mL) and incubated with TgAb samples; Tg was then measured.
  
  
  
  In the clinical study: all patients had residual thyroid tissue, and 10 had metastatic disease. Depending on the TgAb assay, median Tg values were 7.0-10.9, 0.0-5.3, and 0.0-0.0 ng/mL in patients with undetectable, borderline (between functional sensitivities and positive cutoffs), and positive TgAb, respectively (p < 0.001). An undetectable Tg value was associated with borderline levels of TgAb in five assays. Only two patients with metastatic disease had undetectable Tg; both were TgAb positive by three or more assays. Conversely, no patient with undetectable Tg and undetectable or borderline TgAb by sensitive assays had metastatic disease. In the in vitro study, TgAb interfered significantly with Tg recovery (p < 0.001), but low levels of TgAb did not abolish Tg recovery.
  
  
  
  While low levels of TgAb do not preclude Tg measurement in vitro, they can be associated with an undetectable Tg in DTC patients with residual thyroid tissue after thyroidectomy. However, the finding of low levels of TgAb by sensitive assays associated with an undetectable Tg rules out metastatic disease.
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Francesco
authors.initials: F
authors.lastname: Latrofa
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Debora
authors.initials: D
authors.lastname: Ricci
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Eleonora
authors.initials: E
authors.lastname: Sisti
authors.affiliation: 2 Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Phoenix, Arizona.
authors.forename: Paolo
authors.initials: P
authors.lastname: Piaggi
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Chiara
authors.initials: C
authors.lastname: Nencetti
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
authors.affiliation: 1 Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Pisa, Italy .
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002291:Carcinoma, Papillary / Q000097:blood / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013954:Thyroglobulin / Q000097:blood* / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood
chemical_list: D001323:Autoantibodies; D013972:Thyrotropin; D013954:Thyroglobulin