Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease

J Clin Endocrinol Metab. 2012 Apr;97(4):1134-45. doi: 10.1210/jc.2011-2735. Epub 2012 Jan 25.


Context: TSH is the main factor involved in the control of proliferation of thyrocytes. Recently, a strong relationship between serum TSH and risk of thyroid malignancy has been reported.

Objectives: The aim was to review published papers about the relationship between serum TSH and frequency of differentiated thyroid cancer.

Evidence acquisition: PubMed was used to identify studies focused on the relationship between TSH and differentiated thyroid cancer.

Evidence synthesis: In patients with nodular thyroid disease, the risk of thyroid malignancy increases with serum TSH, and even within normal ranges, higher TSH values are associated with a higher frequency and more advanced stage of thyroid cancer. The likelihood of papillary thyroid carcinoma is reduced when TSH is lower, as in thyroid autonomy, and increased when TSH is higher, as in thyroid autoimmunity. Treatment with l-thyroxine (LT4), which reduces serum TSH, is associated with significantly lower risk of developing clinically detectable thyroid cancer.

Conclusions: TSH plays a key role in the development of clinically detectable thyroid cancer, and LT4 treatment reduces the risk of thyroid malignancy in patients with nodular thyroid disease. According to the guidelines of the main scientific societies, LT4 therapy is not currently recommended for the treatment of patients with nodular goiter. Even if the available data are not sufficient to advise LT4 treatment in all patients with nodular goiter with the aim of reducing the risk of papillary thyroid carcinoma, we propose that this indication should be reconsidered, taking into account recent evidence reported in the literature.

MeSH terms

  • Animals
  • Carcinoma
  • Carcinoma, Papillary / blood*
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Papillary / physiopathology*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Practice Guidelines as Topic
  • Risk
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / prevention & control
  • Thyroid Nodule / blood*
  • Thyroid Nodule / drug therapy
  • Thyroid Nodule / physiopathology*
  • Thyroiditis, Autoimmune / blood
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / physiopathology
  • Thyrotropin / antagonists & inhibitors
  • Thyrotropin / blood*
  • Thyroxine / therapeutic use


  • Thyrotropin
  • Thyroxine