Portrait of the Inflammatory Response to Radioiodine Therapy in Female Patients with Differentiated Thyroid Cancer with/without Type 2 Diabetes Mellitus.

No clinical studies have investigated the effect of radioiodine (131I)-targeted therapy on the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as inflammatory response markers in patients with differentiated thyroid cancer (DTC) associated with type 2 diabetes mellitus (T2DM) and obesity. This study aimed to assess the relationship between blood radioactivity, body mass index (BMI), and peripheral blood cells three days after 131I intake in 56 female patients without T2DM (DTC/-T2DM) vs. 24 female patients with T2DM (DTC/+T2DM). Blood radioactivity, measured three days after 131I intake, was significantly lower in the DTC/+T2DM than in the DTC/-T2DM patients (0.7 mCi vs. 1.5 mCi, p < 0.001). The relationship between blood radioactivity and BMI (r = 0.83, p < 0.001), blood radioactivity and NLR (r = 0.53, p = 0.008), and BMI and NLR (r = 0.58, p = 0.003) indicates a possible connection between the bloodstream 131I uptake and T2DM-specific chronic inflammation. In patients without T2DM, 131I therapy has immunosuppressive effects, leading to increased NLR (19.6%, p = 0.009) and PLR (39.1%, p = 0.002). On the contrary, in the chronic inflammation context of T2DM, 131I therapy amplifies immune metabolism, leading to a drop in NLR (10%, p = 0.032) and PLR (13.4%, p = 0.021). Our results show that, in DTC/+T2DM, the bidirectional crosstalk between neutrophils and obesity may limit 131I uptake in the bloodstream. Considering the immune response to 131I therapy, the two groups of patients can be seen as a synchronous portrait of two sides. The explanation could lie in the different radiosensitivity of T and B lymphocytes, with T lymphocytes being predominant in patients with DTC/-T2DM and, most likely, B lymphocytes being predominant in T2DM.

Effects of thyroid hormone withdrawal on natriuretic peptides during radioactive iodine therapy in female patients with differentiated thyroid cancer.

OBJECTIVE: We aimed to investigate the effects of thyroid hormone withdrawal on N-terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC). METHODS: Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT-proBNP were measured in 51 female patients with DTC (48.7 ± 4.2 years) at three time-points: day of radioiodine therapy (t1 - under acute hypothyroidism), 5 days after radioiodine (t2 - under acute hypothyroidism) and 3 months after radioiodine (t3 - under TSH suppression). Thirty healthy euthyroid women served as controls (42.8 ± 5.6 years). RESULTS: At t1/t2/t3, median NT-proANP was 5.2/1.7/487 pmol/L vs. 297.7 pmol/L in control group (p < 0.001), median NT-proBNP was 50.1/36.5/79.5 pmol/L vs. 64.5 pmol/L (p < 0.001) and median NT-proANP/NT-proBNP ratios was 0.20/0.18/4.81 vs. 4.14 (p < 0.001). In acute hypothyroidism, FT3 levels were positively correlated with NT-proANP (r = 0.38, p = 0.005), NT-proANP/NT-proBNP ratios (r = 0.47, p = 0.001), heart rate (r = 0.39, p = 0.005), and negatively with mean arterial blood pressure (r = -0.58, p < 0.001). CONCLUSIONS: Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes.

IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma with/without Hashimoto's thyroiditis.

OBJECTIVE: To investigate the potential role of interleukin 4 (IL-4), interleukin 10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without Hashimoto's thyroiditis (HT). METHODS: Eighty consecutive patients (64 F/16 M, 43.2 ± 12.7 years) with PTC and 40 (37 F/3 M, 40.6 ± 12.3 years) with papillary thyroid carcinoma associated with Hashimoto's thyroiditis (PTC + HT) were evaluated before radioiodine therapy. A control group of 20 patients with HT without thyroid cancer (18 F/2 M, 47.3 ± 2.8 years) was included in the study for the comparison of cytokine levels. RESULTS: No meaningful differences were found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45% persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in patients with persistent/recurrent disease compared to those without recurrence (p < 0.001). IL-4, IL-10 and hs-CRP were also found in substantially higher concentrations in PTC + HT patients with persistent/recurrent disease than in patients with HT or PTC (with or without recurrence) (p < 0.01). Positive correlations were observed between IL-4, IL-10, hs-CRP and thyroglobulin (Tg) (r between 0.48 and 0.56, p < 0.005) or antithyroglobulin antibodies (TgAb) (r between 0.63 and 0.80, p < 0.002) in PTC and PTC + HT patients with persistent/recurrent disease. CONCLUSIONS: Increased levels of serum IL-4, IL-10 and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT patients. Our results suggest that these biomarkers might be used to improve patient stratification according to the risk of recurrence, especially in patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.