Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules

J Endocrinol Invest. 2013 May;36(5):313-20. doi: 10.3275/8579. Epub 2012 Aug 29.


Aim: To assess the relevance of thyroid autoimmunity and TSH as risk factors for malignancy in thyroid nodules (TN).

Subjects and methods: Retrospective analysis on 2053 patients with single/prevalent TN submitted to fine needle aspiration cytology (FNAC). Anti-thyroid autoantibodies (ATA) [anti-thyroperoxidase (TPOAb), anti-thyroglobulin (TgAb)] and TSH were measured. Cytology was classified as benign (class II), indeterminate (class III), and suspicious or malignant (class IV). Histology was available in 301 patients. Associations of malignancy with independent variables were determined by multivariate logistic regression analysis.

Results: Higher prevalence of class IV (14.2% vs 6.8%: p<0.001) and class III (23.5% vs 17.1%: p<0.001) were found in ATA+ vs ATA- TN. Histology confirmed increased prevalence of cancer in ATA+ (p<0.05) TN and in those with diffuse lymphocytic thyroid infiltration (p<0.05). Interestingly, the prevalence of malignancies observed in operated class III nodules was strikingly lower in ATA+ (1/20, 5%), than in ATA- patients (34/67, 50.7%; p<0.001). Increased independent odds ratio (OR) for malignancy was conferred by any ATA [OR 2.21; 95% confidence interval (CI)=1.49-3.29, p<0.0001]; TPOAb (OR 2.15; CI=1.42-3.25, p<0.0001) and TgAb (OR 1.67; CI=1.05-2.67, p<0.05), by serum TSH>1.0 μUI/ml (OR 1.95; CI=1.01-3.76, p<0.05), and by young age (10-29 yr: OR 2.09; CI=1.02-4.26, p<0.05). A formula was calculated to assess the relative contribution of ATA, TSH, and age to the risk of TN malignancy.

Conclusions: Both thyroid autoimmunity and increased TSH represent independent risk factors for TN malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Autoimmunity
  • Biomarkers / blood
  • Female
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Pituitary Gland, Anterior / metabolism
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • Thyroid Gland / immunology*
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / immunology
  • Thyroid Neoplasms / pathology
  • Thyroid Nodule / epidemiology
  • Thyroid Nodule / etiology*
  • Thyroid Nodule / immunology
  • Thyroid Nodule / pathology
  • Thyroiditis, Autoimmune / blood
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / pathology
  • Thyroiditis, Autoimmune / physiopathology*
  • Thyrotropin / blood*
  • Thyrotropin / metabolism
  • Up-Regulation*
  • Young Adult


  • Biomarkers
  • Thyrotropin