Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity

J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa237. doi: 10.1210/clinem/dgaa237.


Background: Higher-but-within-normal thyrotropin (thyroid-stimulating hormone, TSH) is associated with higher risk for differentiated thyroid cancer (DTC) in surgical series. Our recent clinical observations suggest that this is not the case in the presence of autoimmune thyroid disease (AITD). We designed the present study to clarify this controversy.

Methods: We analyzed our prospectively collected database of patients referred for thyroid surgery at 2 tertiary care referral centers in Greece and the United States. We collected data for preoperative TSH, postoperative pathology, and thyroid peroxidase (TPO) antibodies titers. Subjects were subdivided into 2 groups, those with AITD (i.e., lymphocytic thyroiditis) and non-AITD. We excluded subjects with Graves disease, abnormal TSH (< 0.40 or > 4.50 mIU/mL), or recent use of levothyroxine. We compared the serum TSH among different groups using the Mann-Whitney test.

Results: A total of 3973 subjects were screened; 1357 met exclusion criteria. After all exclusions, data from 1731 non-AITD subjects and 329 AITD subjects were included in the analysis. AITD subjects had higher TSH than non-AITD subjects (2.09 vs 1.48; P < 0.0001). TSH values were higher in DTC compared with benign histology only in non-AITD subjects (1.65 vs 1.40; P < 0.0001). Progressively higher TSH was associated with higher incidence of DTC only in non-AITD subjects (P < 0.0001). In AITD subjects, TSH was similar between groups with or without DTC (2.02 vs 2.14; P = 0.21).

Conclusions: TSH concentrations are not associated with the risk of developing DTC in the presence of thyroid autoimmunity, even though this seems to be the case for all other patients.

Keywords: Differentiated thyroid cancer; Hashimoto thyroiditis; TSH; papillary thyroid cancer; thyroid autoimmunity.

MeSH terms

  • Adult
  • Autoantigens / blood
  • Autoimmunity
  • Female
  • Greece / epidemiology
  • Humans
  • Iodide Peroxidase / blood
  • Iron-Binding Proteins / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / complications
  • Thyroid Neoplasms / epidemiology
  • Thyroiditis, Autoimmune / blood*
  • Thyroiditis, Autoimmune / complications
  • Thyroiditis, Autoimmune / epidemiology
  • Thyrotropin / blood*
  • United States / epidemiology


  • Autoantigens
  • Iron-Binding Proteins
  • Thyrotropin
  • TPO protein, human
  • Iodide Peroxidase