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

Our aim was to demonstrate the occurrence of euthyreoid sick syndrome in patients with systemic sclerosis (SSc). Furthermore, the presence of anti-thyroid antibodies and their relationship to thyroid 5'-deiodinase activity was investigated.

The activity of thyroid 5'-deiodinase was measured by 5' outer ring-deiodination using the sera of patients with SSc (n = 21), undifferentiated connective tissue disease (n = 12), and secondary (n = 19) and primary (n = 11) Raynaud's syndrome (RP). Patients with acute cardiovascular events at the time of the study (n = 16) were investigated as controls.

Low FT3 (FT3 < 2.5 pg/ml) was frequently demonstrated in all the patient groups (9/21, 3/12, 10/19 and 8/11, respectively). The high frequency of a FT3/FT4 ratio < 0.2 representing euthyreoid sick syndrome was also often found in SSc (14 cases) and primary (12 cases) and secondary (6 cases) RP patients. Anti-thyroid peroxidase antibody was detected in 17 patients with SSc and in 7, 8 and 3 cases with undifferentiated connective tissue disease, secondary and primary Raynaud's phenomenon, respectively, and in none of the controls. The inhibiting effect of sera on the activity of thyroid 5'-deiodinase was higher in patients with anti-thyroid peroxidase antibodies compared 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) in patients with low FT3.

The low FT3 or FT3/FT4 ratio observed supports the hypothesis that euthyroid sick syndrome is often present in SSc. Anti-thyroid antibody is also frequently detected in SSc and the positive sera inhibit the activity of thyroid 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.