Impaired Thyroid Hormone Sensitivity Linked to Cancer Risk

Miriam E. Tucker, for Medscape

May 30, 2023

The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Impaired sensitivity to thyroid hormones was significantly associated with increased risks for papillary thyroid carcinoma (PTC) and cervical lymph node metastases (LNM) in patients with PTC.

Why This Matters

  • Thyroid cancer has increased rapidly over the past two decades in China; 80% of incident cases are diagnosed as PTC.

  • The pathogenesis of PTC has not been fully clarified.

  • Prior data suggest that reduced sensitivity to thyroid hormone is associated with a variety of physiologic abnormalities. This is the first reported study to investigate the association of thyroid hormone sensitivity with a risk for PTC. Previous studies analyzed the association between thyroid function and PTC by a single index and had inconsistent results.

  • Indices of thyroid hormone sensitivity may be valuable for predicting PTC development and progression pending further data from large, prospective cohort studies. The findings are evidence that multiple indices of thyroid function may be superior to a single index for assessing PTC risk.

Study Design

  • The study was a retrospective study of 1225 patients with PTC and 369 with benign nodules who underwent surgery at a single hospital in Shanghai, China, during 2020.

  • Researchers evaluated thyroid hormone sensitivity using the Thyroid Feedback Quantile-Based Index (TFQI), thyroid-stimulating hormone index (TSHI), and the Thyrotropin Thyroxine Resistance Index (TT4RI).

Key Results

  • People with PTC had significantly higher levels of TSH, TFQI, TSHI and TT4RI compared with those with benign nodules, but thyroid hormone levels didn't differ between the two subgroups.

  • A multivariable analysis that adjusted for age, sex, hypertension, diabetes, smoking status, drinking status, and body mass index showed that the odds ratio for the association between PTC and people in the highest compared with the lowest TFQI tertile was a significant 1.92.

  • Similar adjusted analyses showed a significant odds ratio of 2.33 for the incidence of PTC in the quartile with the highest level of TSHI compared with the lowest quartile and a significant odds ratio of 2.41 for the highest quartile of TT4RI compared with the lowest quartile.

  • Among study participants with PTC, those with cervical LNM had significantly higher levels of TT4RI, TSHI, and TFQI, indicating higher thyroid hormone sensitivity.

  • After multivariate analysis, those with TFQI >0.001 had a significant OR of 1.38 for cervical LNM compared with those with lower TFQI levels. Higher levels of TSHI and TT4RI also significantly associated with cervical LNM.


  • This was a retrospective study.

  • The study included a relatively small number of events.

  • The mechanisms behind the identified associations are not known.


  • The study received no commercial funding.

  • None of the authors had disclosures.

This is a summary of a preprint research study, "Impaired Thyroid Hormone Sensitivity Increases the Risk of Papillary Thyroid Cancer and Cervical Lymph Node Metastasis," by researchers at Zhongshan Hospital Fudan University, Shanghai, China, published on Research Square, and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

Follow Medscape on Facebook, Twitter, Instagram, and YouTube. Have a tip for us? Contact us.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.