TSH suppression therapy promotes tumor progression via G-protein signaling pathways in differentiated thyroid cancerTSH Suppression Therapy Framework for Differentiated Thyroid Cancer

Thyroid-Stimulating Hormone (TSH) suppression therapy is a key strategy in managing differentiated thyroid cancer (DTC) after surgery, but its clinical use has long faced the challenge of a “one-size-fits-all” approach. Previous studies mainly focus on balancing risks and benefits, yet the process of individualized decision-making still lacks systematic integration and synthesis. This article offers a comprehensive review of this issue from an individualized perspective. Mechanistically, it details the networked regulatory mechanisms by which TSH promotes the proliferation, invasion, and dedifferentiation of thyroid cancer cells through the activation of signaling pathways like Gαs and Gαq/11 via TSHR. It also uncovers the complex relationship where TSH collaborates with the key oncogenic drivers to advance tumor growth and the loss of oncogene-induced senescence after long-term stimulation. Clinically, we develop an individualized decision-making framework based on three dimensions: patient factors, tumor traits, and treatment process. Additionally, we synthesize existing evidence to define the benefit boundaries of TSH suppression, aiming to guide clinical practice.