Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism.

OBJECTIVES: Although a single nucleotide polymorphism in a specific receptor for lysophosphatidylserine, a lysophospholipid mediator involved in the immune system, is reportedly associated with Graves' disease, the association between lysophosphatidylserine and thyroid disorders remains to be elucidated. Therefore, we aimed to investigate the association between the level of phosphatidylserine-specific phospholipase A1 (PS-PLA1), which produces lysophosphatidylserine, and thyroid disorders. METHODS: We measured serum PS-PLA1 levels in the patients with various thyroid disorders (n = 120) and normal subjects (n = 58). RESULTS: We observed that the serum PS-PLA1 levels were higher in the subjects with Graves' disease, subacute thyroiditis, or silent thyroiditis, while they were not modulated in the patients with hypothyroidism. The serum PS-PLA1 levels were strongly correlated with the levels of thyroid hormones, especially in the subjects with Graves' disease. Moreover, we found that the serum PS-PLA1 levels were lowered by treatment with anti-thyroid reagents in subjects with Graves' disease and that the changes in PS-PLA1 were strongly correlated with those in thyroid hormones. CONCLUSION: These results suggest that PS-PLA1 might be a novel target in the treatment of hyperthyroidism, especially Graves' disease, and that its measurement might be useful as a supplementary diagnostic test for thyroid function.

Serum autotaxin levels are associated with Graves' disease.

Graves' Disease is a representative autoimmune thyroid disease that presents with hyperthyroidism. Emerging evidence has shown the involvement of lysophosphatidic acid (LPA) and its producing enzyme, autotaxin (ATX), in the pathogenesis of various diseases; among them, the involvement of the ATX/LPA axis in some immunological disturbances has been proposed. In this study, we investigated the association between serum ATX levels and Graves' disease. We measured the levels of serum total ATX and ATX isoforms (classical ATX and novel ATX) in patients with untreated Graves' disease, Graves' disease treated with anti-thyroid drugs, patients with subacute thyroiditis, silent thyroiditis, Plummer's disease, or Hashimoto's thyroiditis, and patients who had undergone a total thyroidectomy, as well as normal subjects. The serum total ATX and ATX isoform levels were higher in the patients with Graves' disease, compared with the levels in the healthy subjects and the patients with subacute thyroiditis. Treatment with anti-thyroid drugs significantly decreased the serum ATX levels. The serum ATX levels and the changes in serum ATX levels during treatment were moderately or strongly correlated with the serum concentrations or the changes in thyroid hormones. However, the administration of T3 or T4 did not increase the expression or serum levels of ATX in 3T3L1 adipocytes or wild-type mice. In conclusion, the serum ATX levels were higher in subjects with Graves' disease, possibly because of a mechanism that does not involve hyperthyroidism. These results suggest the possible involvement of the ATX/LPA axis in the pathogenesis of Graves' disease.