The role of the hypothalamic–pituitary–thyroid axis in thyroid cancer

The hypothalamic–pituitary–thyroid axis plays a crucial role in the pathogenesis, diagnosis, risk stratification, effectiveness of radioiodine therapy, and treatment response evaluation in epithelial thyroid cancer. Supraphysiological doses of levothyroxine are used in patients with intermediate-risk and high-risk thyroid cancer to suppress thyroid-stimulating hormone (TSH) to prevent tumour progression. However, free thyroxine and tri-iodothyronine have also been found to promote tumour growth in thyroid cancer preclinical models. Moreover, current evidence remains inconclusive about the role of TSH suppression in improving survival outcomes and reveals an increased risk of cardiovascular and skeletal adverse events after long-term exposure to excess levothyroxine. Stimulation of the axis with either recombinant human TSH or thyroid hormone withdrawal has been proven equally effective for diagnostic purposes and for facilitating radioiodine uptake for thyroid remnant ablation, but evidence is insufficient for non-inferiority of recombinant human TSH-based vs thyroid hormone withdrawal-based stimulation before radioiodine therapy of distant metastases.