Opposing effects of thyroid hormones on cancer risk: a population-based study

Abstract

Objective: The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types. Design and methods: Data on thyroid hormone profile was collected from 375,635 Israeli patients with no prior history of cancer. Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as twenty cancer subgroups. Results: 23,808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increase cancer risk (HR 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR 0.67). Log TSH elevation was associated with decreased risk of thyroid cancer (HR 0.82) and increased risk of melanoma (HR 1.11) and uterine cancer (HR 1.27). Elevated free T4 was associated with increased lung cancer risk (HR 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR 0.59 and 0.08, respectively). Conclusions: Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

Prostate gland as a target organ of thyroid hormones: advances and controversies

“…T3 is an important regulator of androgen signaling, and more specific studies must be performed to discriminate between androgen-dependent and independent mechanisms. TH effects on cancer progression seem to be divergent and depend on the tumoral environment ( 51 , 75 ). As previously reviewed, THs exert dual actions.…”

“…There is evidence that subclinical or overall hypothyroidism does not modify the risk of prostate cancer, while hyperthyroidism or reduced levels of TSH significantly increase this risk when these parameters are age-adjusted and with any other potential confounder factor [reviews: ( 50 , 51 , 52 , 53 , 54 )]. A prospective study (326 cases/9981 patients) showed that subclinical and frank hypothyroidisms are not associated with cancer risk ( 50 ).…”

The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications

“…23808 cases of cancer were detected over a median follow-up of 10 years. Interestingly, among patients who developed PCa (2,406 over 16,9554 males), elevated TSH levels were associated with decreased risk of PCa, yielding an HR of 0.67 (85). Tran et al found similar data, reporting a significant association between hyperthyroidism and PCa (HR = 1.35) (40) and Mondul et al reported a decreased risk of PCa in men with higher serum TSH compared to men with lower TSH, yielding an Odds Ratio (OR) = 0.70.…”

The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum

“…Among patients aged less than 50 years old at inclusion, TSH levels in the hyperthyroid range, elevated fT4 levels, and subclinical hyperthyroidism were associated with an increased cancer risk (HR, 1.3, 1.28, and 1.31, respectively). Increased TSH levels were correlated with a decreased risk of prostate cancer (HR, 0.67), while log-TSH elevation was associated with an increased risk of melanoma (HR, 1.11) and uterine cancer (HR, 1.27) [ 91 ].…”