Background
Pretibial myxedema (PTM) or, more appropriately, thyroid dermopathy is a term used to describe localized lesions of the skin resulting from the deposition of hyaluronic acid, usually as a component of thyroid disease. Although the condition is most often confined to the pretibial area, it may occur anywhere on the skin. It is nearly always associated with Graves disease (see Graves Disease for more information).
Additionally, a Medscape CME course related Graves disease is Therapy Insight: Management of Graves' Disease During Pregnancy.
Pathophysiology
PTM occurs as a result of the deposition of hyaluronic acid in the dermis and subcutis. The precise cause of this phenomenon remains uncertain. A leading theory proposes that fibroblasts are stimulated to produce abnormally high amounts of glycosaminoglycan due to exposure to thyroid hormones. Both thyrotropin and thyrotropin receptor antibody binding sites are found in the plasma membranes of fibroblasts derived from the skin of patients with PTM. Long-acting thyroid stimulator (LATS), an immunoglobulin G (IgG) antibody, is present in the serum of almost all patients with PTM, but it has also been found in the serum of patients without PTM. LATS was later demonstrated to represent thyrotropin receptor autoantibodies.
Research published in 2006 suggests that it may be more than the high level of glycosaminoglycans, but the change in percentage of the constituents of the glycosaminoglycans in the blood that leads to the development of PTM. Thyroid hormones, by means of their influence on prostaglandin metabolism, alter the synthesis and degradation of glycosaminoglycans. Prostaglandin degradation may be what is changed in the course of Graves disease, based on findings that glycosaminoglycan synthesis is reduced, as is extracellular matrix assembly in vitro with exposure to T3 excess.[1]
Cell-mediated immunity, using differentially expressed T-cell surface receptors in localized PTM, has also been proposed as having a causative role.[2] The fact that PTM frequently develops in areas of injury suggests that trauma may contribute to local fibroblast activation. In addition, extrathyroid manifestations of Graves disease often occur in the skin and eyes — fibroblasts within the orbits and skin were found to have phenotypic differences from other fibroblasts throughout the body.
Epidemiology
Frequency
United States
PTM occurs in 0.5-4.3% of patients with Graves disease. PTM has also been reported in patients with Hashimoto thyroiditis, primary hypothyroidism, and euthyroidism. Peak incidence occurs in the fifth to sixth decades of life.
Mortality/Morbidity
PTM is primarily of cosmetic concern and rarely causes significant morbidity. Local discomfort and difficulty wearing shoes are expected.
Sex
Women are affected more frequently than men, with a female-to-male ratio of 3.5:1.
Age
PTM may occur in children and young adults, but most cases occur in older adults, with a peak age at onset in the fifth to sixth decades of life.
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