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

Clin Exp Rheumatol. 2000 Nov-Dec;18(6):719-24.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Acute Disease
  • Adult
  • Antibodies / analysis
  • Blood Physiological Phenomena
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / enzymology
  • Connective Tissue Diseases / blood
  • Connective Tissue Diseases / complications
  • Connective Tissue Diseases / enzymology
  • Euthyroid Sick Syndromes / etiology*
  • Female
  • Humans
  • Iodide Peroxidase / antagonists & inhibitors*
  • Iodide Peroxidase / immunology
  • Iodide Peroxidase / metabolism
  • Male
  • Middle Aged
  • Raynaud Disease / blood
  • Raynaud Disease / enzymology
  • Raynaud Disease / etiology
  • Scleroderma, Localized / blood
  • Scleroderma, Localized / complications*
  • Scleroderma, Localized / enzymology*
  • Scleroderma, Localized / immunology
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / enzymology*
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / metabolism
  • Thyroid Gland / enzymology*
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Antibodies
  • Triiodothyronine
  • Iodide Peroxidase
  • Thyroxine