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
Authors: Díez Juan J. , Hernanz Angel , Medina Sonia , Bayón Carmen , Iglesias Pedro 
Published: March 2003

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.