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.
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.
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 hypothyroidism prior to diagnosis while 5/265 (1.9%) patients presented with hyperthyroidism. While history of hyperthyroidism was not associated with survival prognosis (p = 0.487; log rank test), patients with hypothyroidism had an improved survival prognosis upon BM diagnosis (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) in multivariate analysis including GPA 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).
Preexisting hypothyroidism had 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.
Clinical trial identification
Legal entity responsible for the study
Medical University of Vienna.
Has not received any funding.
All authors have declared no conflicts of interest.