Hypothyroidism is associated with improved survival prognosis in patients with newly diagnosed brain metastases

Abstract

Background: Thyroid hormones may have tumor promoting effects due to the increased activity of phosphatidylinositol-3-kinase and induction of angiogenesis. Lower TSH levels, representing excessive thyroid function, were associated with increased risk for several tumor types, whereas hypothyroidism was shown to have the opposite effect. However, only limited knowledge exists on the prognostic impact in patients with advanced cancer. Given the difficulties in prognostic assessment in patients with newly diagnosed brain metastases (BM) we aimed to investigate the prognostic impact of thyroid function. Methods: Patients with newly diagnosed BM were identified from the Vienna Brain Metastasis Registry and clinical data including survival data, thyroid stimulating hormone (TSH) and free thyroxine (fT4) were retrieved by chart review. Results: 265 patients (191/265 (72.1%) non-small cell lung cancer; 74/265 (27.9%) triple negative breast cancer) with a median age of 59 years (range 26-85) at diagnosis of BM were available for analysis. 22/265 (8.3%) patients presented with a history of hypothyroidismprior to diagnosis while 5/265 (1.9%) patients presented with hyperthyroidism. While history of hyperthyroidismwas not associated with survival prognosis (p=0.487; log rank test), patientswith hypothyroidismhad an improved survival prognosis upon BMdiagnosis (8 vs. 14 months; p=0.032; log rank test). Pre-existing hypothyroidism presented with independent statistically significant association with survival prognosis (HR 0.6; 95% CI 0.4-0.9; p=0.025) inmultivariate analysis includingGPA class (HR 1.6; 95%CI 1.3-1.9; p<0.001) and tumor type (HR 1.5; 95%1.1-2.0; p=0.006). Conclusions: Preexisting hypothyroidismhad a strong and independent prognostic impact in patients with newly diagnosed BM underscoring the evidence from pre-clinical data that thyroid hormones might indeed impact tumor growth. Further investigation of the underlying mechanism is warranted to identify a possible therapeutic impact.