Euthyroid sick syndrome and inhibitory effect of sera on the activity of thyroid 5 '-deiodinase in systemic sclerosis

Objective Our aim was to demonstrate the occurrence of euthyreoid sick syndrome in pa tients with systemic sclerosis (SSc). Furthermore, the presence of anti-thy roid antibodies and their relationship to thyroid 5'-deiodinase activity wa s investigated. Methods The activity of thyroid 5'-deiodinase was measured by 5' outer ring-deiodin ation using the sera of patients with SSc (n = 21), undifferentiated connec tive tissue disease (n = 12), and secondary (n = 19) and primary (n = 11) R aynaud's syndrome (RP). Patients with acute cardiovascular events at the ti me of the study (n = 16) were investigated as controls. Results Low FT3 (FT3 < 2.5 pg/ml) was frequently demonstrated in all the patient gr oups (9/21, 3/12, 10/19 and 8/11, respectively). The high frequency of a FT 3/FT4 ratio < 0.2 representing euthyreoid sick syndrome was also often foun d in SSc (14 cases) and primary (12 cases) and secondary (6 cases) RP patie nts. Anti-thyroid peroxidase antibody was detected in 17 patients with SSc and in 7, 8 and 3 cases with undifferentiated connective tissue disease, se condary and primary Raynaud's phenomenon, respectively, and in none of the controls. The inhibiting effect of sera on the activity of thyroid 5'-deiod inase was higher in patients with anti-thyroid peroxidase antibodies compar ed to antibody negative cases (P < 0.01). An inverse correlation was shown between the levels of anti-thyroid peroxidase antibodies and the decreased activity of thyroid 5'-deiodinase (r = - 0.6111, P < 0.02) inpatients with low FT3. Conclusion The low FT3 or FT3/FT4 ratio observed supports the hypothesis that euthyroi d sick syndrome is often present in SSc. Anti-thyroid antibody is also freq uently detected in SSc and the positive sera inhibit the activity of thyroi d 5'-deiodinase, which can contribute to the low FT3 or FT3/FT4 ratio. Anti -thyroid peroxidase antibodies may play an additive role in the development of low FT3 levels via the inhibiting effect of thyroid 5'-deiodinase. The low FT3 levels may directly influence the already impaired microcirculation in SSc by increasing the systemic vascular resistance.