Serum concentrations of tumour necrosis factor-alpha (TNF-α) and soluble TNF-α receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function

Abstract

BACKGBOUND: Tumour necrosis factor-α (TNF-α) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-α have been demonstrated in thyroid follicular cells and TNF-α and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-α have been reported to be elevated and administration of TNF-α to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. OBJECTIVE: To evaluate serum concentrations of TNF-α and the soluble receptor for TNF-α (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. DESIGN: We studied 20 patients with hypothyroidism (18 women and 2 men, mean age ± SD, 48.8 ± 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 ± 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 ± 15.1 years) were also studied as a control group. SETTING: All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. MEASUREMENTS: Serum concentrations of free T4 (FT4), total T3, TSH, TNF-α and sTNFR-I were measured in all subjects. TNF-α and sTNFR-I were measured using a quantitative enzyme immunoassay. RESULTS: In patients with hypothyroidism serum concentrations of TNF-α (3.17 ± 1.18 pg/ml) and sTNFR-I (1273 ± 364 pg/ml) were significantly higher than those found in controls (2.42 ± 0.76 pg/ml, P < 0.05, and 971 ± 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with L-thyroxine therapy did not significantly modify TNF-α or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-α and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-α (3.36 ± 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 ± 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-α levels (2.46 ± 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 ± 475 pg/ml; P < 0.001). Post-therapy levels of TNF-α and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism. CONCLUSIONS: In summary, these results confirm the relevance of activation of the TNF-α system in patients with thyroid dysfunction, as high plasma concentrations of TNF-α and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-α and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.