Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective

Abstract

Thyroid hormones (THs) may play a role in diseases other than hyper-and hypothyroidism. Several lines of evidence suggest tumor-promoting effects of TH and TH receptors. They are possibly mediated by phosphatidylinositol-3-kinase and MAPK and involve among others stimulation of angiogenesis via avb3. Thus, an increased risk for colon, lung, prostate, and breast cancer with lower TSH has been demonstrated in epidemiological studies, even suggesting a TH dose effect on cancer occurrence. Furthermore, higher TH levels were associated with an advanced clinical stage of breast and prostate cancer. In rodent models, TH stimulated growth and metastasis of tumor transplants, whereas hypothyroidism had opposite effects. In clinical studies of glioblastoma and head and neck cancer, hypothyroid patients showed longer survival than euthyroid patients. Also, patients with renal cell cancer that were treated with the tyrosine kinase inhibitor sunitinib and developed hypothyroidism in due course showed significantly longer survival than patients that remained euthyroid. Development of hypothyroidism was an independent predictor for survival in two studies. Yet, it is still possible that hypothyroidism is only a surrogate marker for treatment efficacy and does not positively influence treatment outcome by itself. Future cancer treatment studies, especially with substances that can induce hypothyroidism, should therefore be designed in a way that allows for an analysis of thyroid function status and its contribution on treatment outcome.

Elevated serum levels of free triiodothyronine in adolescent boys with gynaecomastia compared with controls

“…The presence of thyroid hormone receptor alpha (THRa) has been demonstrated Furthermore, thyroid hormones exert effects on breast cancer cells in vitro (19,20). In accordance, a very recent study has demonstrated the presence of both THRa and THRb in breast cancer cells (21).…”

Hormony tarczycy w ośrodkowym układzie nerwowym (OUN) i ich wpływ na nowotworzenie, zwłaszcza na rozwój i przebieg glioblastoma multiforme — hipoteza badawcza

“…These mechanisms vary between different organs and depend on the period of human body development. All of these TH effects, however, are disturbed in the majority of types of neoplasms [14][15][16].…”

“…Some recent review papers [15,16] focusing on the participation of thyroid hormones and their receptors in neoplasm development and the course of neoplastic diseases gave evidence indicating that the current hyperthyroidism, or the past history of thyroid hyperactivity increase the risk of developing various neoplasms and affect the course of the developed neoplastic diseases. The heterogeneity of this phenomenon was also presented: in liver cancer, as opposed to other neoplastic diseases, hypothyroidism was a risk factor.…”

“…Te mechanizmy działania są zróżnicowane narządowo i zależne od okresu rozwojowego organizmu. Zaburzenia tych efektów działania TH są charakterystyczne dla wszystkich rodzajów nowotworów [14][15][16].…”

“…W pracach poglądowych dotyczących udziału hormonów tarczycy i ich receptorów w nowotworzeniu i przebiegu chorób nowotworowych [15,16] przedstawiono wyniki badań wskazujące, że aktualna hypertyreoza lub przebyta w przeszłości nadczynność tarczycy zwiększa ryzyko pojawienia się u człowieka różnych nowotworów i wpływa na ich przebieg. Przedstawiono również heterogenność tego zjawiska, a mianowicie w raku wątroby w odróżnieniu od innych nowotworów czynnikiem ryzyka była niedoczynność tarczycy.…”