Fibroblast biology in thyroid diseases

Abstract

Several thyroid diseases are manifested by structural and functional alterations in connective tissue. Hypothyroidism in its more severe and sustained form results in generalized deposition of the glycosaminoglycan hyaluronan in many tissues. This condition is termed myxedema and is easily remedied by correcting the thyroid hormone deficiency. In contrast, a common form of hyperthyroidism, Graves' disease, involves hyaluronan accumulation localized in the orbital tissues surrounding the eye and the subcutaneous tissues of the anterior shin. Graves' disease is an autoimmune disorder where antibodies are generated to the thyrotropin receptor. Moreover the affected areas of the body, including the thyroid and orbit, become infiltrated with activated T lymphocytes and mast cells. It is currently believed that fibroblasts are the most important source for hyaluronan in both hypothyroidism and Graves' disease. Why two thyroid maladies involving very different pathogenic mechanisms might present with disordered hyaluronan accumulation is not known. This brief review will examine activated fibroblasts as important mediators of connective tissue remodeling associated with hypothyroidism and Graves' disease. The weight of the current evidence strongly implicates these cells as central players in the pathogenesis of both of these examples of thyroid dysfunction.