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Background: Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer., Methods: We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich., Results: Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed., Conclusion: Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required., Competing Interests: Conflict of interest statement A.S.B. has received research support from Daiichi Sankyo (≤10000€), Roche (>10000€); has received honoraria for lectures;has been a member of the consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all < 5000€), has received travel support from Roche, Amgen and AbbVie. M.K. has received research support from Sanofi, AstraZeneca and Ipsen; served as a speaker and received consulting fees from AstraZeneca, Novartis, Novo Nordisk, Lilly, Merck, Böhringer, Roche and Sanofi. M.W. has received research grants from Abbvie, Adastra, Bristol Meyer Squibb (BMS), Dracen, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Piqur and Roche; has received honoraria for lectures or served as a member of advisory board participation or consulting from Abbvie, Basilea, Bristol Meyer Squibb (BMS), Celgene, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Roche and Tocagen. M.P. has received research support from Böhringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche; has received honoraria for lectures; served as a member of the consultation or advisory board participation (all < 5000€) from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. All the other authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)