**5. Glioblastoma**

In preclinical studies, T4 has been shown to be a growth factor for gliomas [21], and the actions of chemically modified tetrac molecules at the thyroid hormone receptor on integrin αvβ3 significantly increased transcription of a panel of proapoptotic genes (*p53*, *p21*, *PIG*, *BAD*) [7]. The latter results imply that T4 action at the integrin may undesirably either decease or not affect expression of these genes. In a limited *in vitro* study, T3 restricted glioblastoma cell proliferation [42] and preclinical studies have also shown that NDAT—which limits access of T4 to its receptor on integrin αvβ3 on tumor cells—suppresses growth and is anti-angiogenic in glioblastoma xenografts [25].

In 2003, chemical induction of mild hypothyroidism with propylthiouracil (PTU) was shown in patients with recurrent, high-grade glioblastoma to be associated with significant prolongation of survival [43]. More recently, euthyroid hypothyroxinemia has significantly extended survival in patients with end-stage glioblastoma [27].

Induction of euthyroid hypothyroxinemia has been effective in prolonging survival of the few glioblastoma patients with end-stage disease in whom it has been tested [27].
