Thyroid Hormone Replacement Therapy in Patients with Various Types of Cancer

Abstract

Primary hypothyroidism is a common endocrine disorder that is effectively treated with l-thyroxine (T4) replacement. Preclinical and limited clinical evidence, however, indicates that T4 is a growth factor for a variety of cancers, acting at the thyroid hormone receptor on plasma membrane integrin αvβ3. T4 is the primary ligand for this receptor, whereas 3,5,3′-triiodo-l-thyronine (T3) is the principal intracellular thyroid hormone analogue. The evidence is reviewed here that T4 is a proliferative for breast, lung, kidney and prostate cancers and for glioblastoma, regulates cancer cell respiration and is a pro-angiogenic factor in established tumors. The recommendation is made that T3 be considered alternative replacement treatment for patients with primary hypothyroidism who also have cancer.

Clinical Implications and Impact of Discovery of the Thyroid Hormone Receptor on Integrin αvβ3–A Review

“…Similarly, blocking of the receptor with tetrac effectively blocks all (most) T4 and T3 signal transduction as occurs following T4 and T3 depletion. This results in regression of established tumors, inhibits angiogenesis, and potentiates ionizing radiation-induced cell death (2). Separation and divergence of the effects and functions of T4 from T3 on integrin αvβ3-expressed receptors occurs as a result of binding to the receptor.…”

“…T3-directed gene expression in cells requires primary interactions between T3 and its nuclear receptor proteins (TRs) (1, 2). T3 also regulates mitochondrial respiration (3).…”

“…More information available about T4 action on lung cancer is limited, but euthyroid hypothyroxinemia appears to slow the course of and extend survival of non-small cell, small cell lung, pancreas, mesothelioma, glioblastoma, and soft tissue sarcoma (1, 2).…”

“…In recent years there have been reports that blood thyroxine depletion in individuals with advanced solid cancers–e.g., glioblastoma, high grade soft tissue sarcoma, was associated with regression of advanced tumors. Exogenous 3,5,3′-triiodo-L-thyronine (L-T3) was used to maintain metabolic euthyroidism (1, 2).…”

Main Factors Involved in Thyroid Hormone Action

“…The effects of THs when αvβ3 is pathologically overexpressed were evaluated [ 57 ] and tetrac or its modified forms (tetrac analogues, nanoparticles formulations) were used for the pharmacological blockade of T4 action at αvβ3 integrin on different cell types [ 58 , 59 , 60 , 61 , 62 , 63 ].…”