The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum

Hypothyroidism in patients with solid non-thyroid cancer is a tantalizing entity, integrating an intriguing thyroid hormones (THs)–cancer association with the complexity of hypothyroidism itself. The present narrative review provides a comprehensive overview of the clinical relevance of hypothyroidism in solid non-thyroid cancer. Hypothyroidism in patients with solid non-thyroid cancer is reminiscent of hypothyroidism in the general population, yet also poses distinct challenges due to the dual role of THs in cancer: promoting versus inhibitory. Close collaboration between oncologists and endocrinologists will enable the prompt and personalized diagnosis and treatment of hypothyroidism in patients with solid non-thyroid cancer. Clinical data indicate that hypothyroidism is a predictor of a decreased or increased risk of solid non-thyroid cancer and is a prognostic factor of favorable or unfavorable prognosis in solid non-thyroid cancer. However, the impact of hypothyroidism with respect to the risk and/or prognosis of solid non-thyroid cancer is not a consistent finding. To harness hypothyroidism, or THs replacement, as a personalized anticancer strategy for solid non-thyroid cancer, four prerequisites need to be fulfilled, namely: (i) deciphering the dual THs actions in cancer; (ii) identifying interventions in THs status and developing agents that block tumor-promoting THs actions and/or mimic anticancer THs actions; (iii) appropriate patient selection; and (iv) counteracting current methodological limitations.