Thyroid cancer, as a highly hormone-dependent malignancy, is significantly regulated by thyroid hormones (T3/T4) and thyroid-stimulating hormone (TSH) signaling in its initiation and progression. This article comprehensively reviews the roles of thyroid hormones and their regulatory factor TSH in thyroid carcinogenesis and development, addressing related research from molecular mechanisms and clinical correlations to therapeutic strategies. It focuses on elucidating the impact of key mechanisms—such as elevated integrin αvβ3 expression and TRβ receptor mutations under hyperthyroid or hypothyroid conditions—on tumor progression. Furthermore, it evaluates the clinical utility and potential risks of TSH suppression therapy in patients stratified by risk, aiming to provide a theoretical basis for optimizing individualized treatment strategies.

Thyroid cancer (TC) is an endocrine malignant tumor with the fastest-growing incidence worldwide. It has complex pathological types and significant heterogeneity, with great differences in clinical prognosis among different subtypes. Among them, aggressive subtypes, such as radioiodine-refractory (RAI-R) TC and anaplastic thyroid cancer (ATC), have become a major challenge in current clinical diagnosis and treatment, due to limited treatment options and high risks of recurrence and metastasis. Tumor metabolic reprogramming is one of the characteristics of cancer, among which the Warburg effect plays a driving role. As a rate-limiting enzyme in the glycolytic pathway, pyruvate kinase M2 (PKM2), with its unique functional plasticity, has become a linchpin of glycolytic metabolism and malignant phenotypes of tumor cells. This article will systematically review the functional regulatory mechanisms of PKM2, its specific role in TC, and explore the targeted therapeutic strategies and research prospects of TC with PKM2, providing a new theoretical basis and potential plans for the clinical diagnosis and treatment.