The impact of thyroid hormones on patients with hepatocellular carcinoma

Abstract

Background & aimsHypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients.MethodsOf 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated.ResultsThyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9–15.7 months) vs. 7.3 months (5.4–9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5–13.6 months) vs. 3.3 months (2.2–4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3–3.3); p = 0.002) in multivariate analysis.ConclusionsTSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

Thyroid Hormones and Cancer: A Comprehensive Review of Preclinical and Clinical Studies

“…Compared with euthyroid subjects, hypothyroid patients had higher likelihood of advanced colonic disease (8.3 vs. 4.4%, p = 0.028) (185). In another study by Pinter et al, 667 patients diagnosed with non-surgically treated HCC were retrospectively followed for a mean period of 65.5 months (190). Hypothyroid patients (TSH>3.77 μU/ml) had a higher risk for large lesions (>5 cm), while Hyperthyroid patients (TSH<0.44 μU/ml) had a lower risk.…”

<p>Use of a Novel Thyroid-Stimulating Hormone Model for Predicting the Progression of Hepatocellular Carcinoma</p>

“…33 The studies have found that patients with high levels of TSH, the larger the tumor, the worse the prognosis. 34 In contrast, another independent study has shown that higher TSH or FT4 in the blood is associated with better clinical outcomes in HCC patients receiving chemotherapy. 25 Therefore, in our prospective cohort, we found that TSH level was associated with HCC progression, and patients with a high TSH level were at risk of tumor progression.…”

The Molecular Function and Clinical Role of Thyroid Stimulating Hormone Receptor in Cancer Cells

“…According to current understandings in this field, most of the literature has considered T3/T4 a potential tumor suppressor, while others have considered them to be oncogenic promoters in HCC (for a comprehensive review of the effects of thyroid hormones in HCC, see [112]). Some of these studies provided a possible explanation for the finding that higher TSH and free T4 levels in blood were associated with poorer prognoses and larger tumor size in unresectable HCC patients [113]. Intriguingly, another independent study showed that higher TSH or free T4 concentrations in blood were associated with better clinical outcomes in HCC patients receiving chemotherapy, but not sorafenib (a targeted anticancer drug) treatment [114].…”

“…As such, unless a specific liver or ovarian cancer delivering or targeting system can be developed, the TSHR-targeting strategy cannot be applied to extra-thyroid cancers. However, by use of the index obtained from the levels of TSH and free T4, one can select a better strategy to treat patients with HCC [113,114].…”