Endocrine Abstracts

Objectives: Differentiated thyroid cancer (DTC) accounts for over 95% of thyroid malignancies. It has been reported that integrin αvβ3, fractalkine, and CX3CR1 expression were upregulated in patients with papillary thyroid carcinoma (PTC). L-thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. In patients with DTC, thyroid hormone suppression therapy (THST) with T4 has been associated with a higher risk of cardiovascular mortality. The purpose of this study was to assess a possible association between molecular markers and sympathetic-parasympathetic balance assessed via heart rate variability (HRV), both at baseline and under THST, in patients newly diagnosed with PTC with no significant comorbidities.

Methods: This prospective study included 36 PTC and 14 benign nodular goiter (BNG) patients who were euthyroid preoperatively. Molecular markers assessments included the following parameters: integrin αvβ3, fractalkine, and CX3CR1. The analysis of HRV included both time-domain parameters and frequency-domain parameters. After at least 6 months of THST, patients with PTC were reassessed for molecular markers and HRV parameters.

Results: PTC and BNG groups were similar in terms of age, gender, and BMI (P = 0.184; P = 0.705; P = 0.749, respectively). Serum integrin αvβ3 level was significantly higher in the PTC group (24.27±8.01 ng/ml; 17.25±7.27 ng/ml; P = 0.006). Other serum molecular marker levels were similar in both groups. Significant decreases were observed in HRV parameters including HF, LF, VLF, SDNNi, rMSSD, SDSD, and pNN50 under THST. In the PTC group, frequency-domain HRV analysis showed the following correlations: 1) lower HF values with higher CX3CR1 (r =-0.42, P = 0.011); 2) lower LF values with higher CX3CR1 (r= -0.45, P = 0.007); 3) lower VLF values with higher CX3CR1 (r =-0.35, P = 0.034). In multivariate regression, CX3CR1, and integrin αvβ3 were revealed to be independently related to the LF/HF ratio (B=0.002, P = 0.003; B=-0.107, P= 0.026; B=0.256, P = 0.026, respectively) in patients with PTC baseline. Under THST, only CX3CR1 was found to be associated with an LF/HF ratio independent of TSH level (B=0.001, P = 0.036).

Conclusions: The study showed that serum integrin αvβ3 levels were significantly higher in patients with PTC compared to the BNG. There was a relationship between sympathetic-parasympathetic balance assessed via HRV and molecular markers particularly CX3CR1 and integrin αvβ3 in patients with PTC. We found that CX3CR1 was an independent marker of autonomic nervous system dysfunction in patients with PTC under THST.