Myxedema describes a specific form of
cutaneous and
dermal edema secondary to increased deposition of
connective tissue components. The connective fibres are separated by an increased amount of protein and mucopolysaccharides. This protein-mucopolysaccharide complex binds water, producing non-pitting boggy edema, in particular around eyes, hands, feet and in the supraclavicular fossae. This deposition involves not only the skin but also the tongue, myocardium, kidney medulla, lung, intestine and most other organs of the body (apart from the stomach). Myxoedema is also responsible for the thickening of the laryngeal and pharyngeal mucous membranes, which results in thick slurred speech and hoarseness, both of which are seen commonly in hypothyroidism. The accumulation of
glycosaminoglycans (GAGs) in the dermal tissues consists characteristically of
hyaluronic acid with very little change in the dermatan sulfate abundance and perhaps a decrease in chondroitin sulfate. The pathogenesis of generalized myxedema is thought to be fairly well understood and related to the deficiency of thyroid hormone, but the pathogenesis of pretibial and orbital myxedema due to Grave's disease is not fully understood, however, two mechanisms predominate: •
Fibroblast stimulation. It is thought that fibroblast stimulation by the
thyroid stimulating hormone (TSH) receptor increases the deposition of glycosaminoglycan, which results in an osmotic
edema and fluid retention. It is thought that many cells responsible for forming connective tissue react to increases in TSH levels. •
Lymphocyte stimulation. In Graves' thyroid disease, lymphocytes react against the TSH receptor by inappropriately producing thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity). Lymphocytes react not only against thyroid receptors, but also any tissue with cells expressing the receptor. This can lead to tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans. ==Diagnosis==