myxedema

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Myxoedema
Classification and external resources
Hyaluronan, an example of a mucopolysaccharide.
ICD-10	E03.9
ICD-9	244.9
DiseasesDB	6558
MedlinePlus	000353
eMedicine	med/1581 derm/347
MeSH	D009230

Hypothyroid type myxedema (British English: myxoedema) describes a specific form of cutaneous and dermal non-pitting edema secondary to increased deposition of connective tissue matrix components (like glycosaminoglycan, hyaluronic acid, and other mucopolysaccharides). In Graves' disease the myxedema is secondary to lymphocytic infiltrate and secondary swelling from inflammatory reactions and is typically located in the periorbital tissues, extraocular muscles and in the lower legs, mostly below the knee (pretibial myxedema).^[1]:535 While both hyper- and hypo- thyroidism have forms of myxedema their etiologies are pathophsiologically distinct.

Terminology

The word originates from μύξα, taken from ancient Greek to convey 'mucus' or 'slimy substance' and ὁίδημα for swelling. Myxedema is also a clinical state that is intermediate between cretinism of children and hypothyroidism of adults. Clinical features of myxedema are characterized by a slowing of physical and mental activity. Symptoms include depression, mental sluggishness, listlessness, cold intolerance, obesity, constipation and decreased sweating secondary to decreased sympathetic nervous system output, and also reduced cardiac output that contributes to shortness of breath and exercise intolerance. ^[2]

The term can be a cause for confusion but it should not be confused with a form of myxedema seen in Graves' disease and hyperthyroid states which does not include the mental sluggishness and listless state of the aforementioned hypothyroid myxedema. In the context of hyperthyroidism, pretibial myxedema typically presents in the lower limb (below the knee) and periorbital myxedema leads to the exophthalmos (bulging eyes), both of which include autoimmune mechanisms and T cells that are not a contributing factor in hypothyroid myxedema.

Causes

Hypothyroidism

• The skin in hypothyroidism is cool and dry. Normally, the skin contains a variety of proteins complexed with polysaccharides, chondroitin sulfuric acid and hyaluronic acid. In hypothyroidism, these complexes accumulate, promoting sodium and water retention and producing a characteristic diffuse, non-pitting puffiness of the skin (myxedema). The person's face appears puffy, with coarse features. Similar accumulation of mucopolysaccharides in the larynx may lead to hoarseness. The hair is brittle and lacking luster, and there is frequently loss of body hair, particularly over the scalp and lateral thirds of the eyebrows. If the thyroid hormone is replaced therapeutically, the protein complexes are mobilized and a diuresis ensues and the myxedema resolves. Carotenemia (yellow-orange skin) can occur because thyroid hormone is needed by the liver to convert carotene to vitamin A. In the absence of sufficient hormone, carotene accumulates in the bloodstream and skin.
• In long-standing hypothyroidism a condition called myxedema coma may occur. Patients have typical myxedematous facies and skin, bradycardia, hypothermia, alveolar hypoventilation and severe obtundation or coma. This condition is usually precipitated by an intercurrent illness such as an infection or stroke or by a medication such as a sedative-hypnotic. The mortality rate approaches 100% unless myxedema coma is recognized and treated promptly.^[3]

Hyperthyroidism

• The wide-eyed stare in hyperthyroidism is in part due to increase sympathetic tone. Proptosis develops in about half of Graves' disease persons as a result of infiltration of orbital soft tissues and extraocular muscles with lymphocytes, mucopolysaccharides and edema fluid. This may lead to fibrosis of the extraocular muscles, restricted ocular motility and diplopia. In severe Graves' opthalmopathy, pressure on the optic nerve or keratitis from corneal exposure may lead to blindness. In patients with Graves' disease, it is clear that thyroid stimulating antibody is related to Graves' ophthalmopathy. In addition, auto-antibodies against G2s are identified in significantly more patients with active thyroid ophthalmopathy than in patients with Graves' disease without ophthalmopathy, those with Hashimoto's thyroiditis or non-immunological thyroid disorders, and those without thyroid disease. The pathogenesis of Graves' ophthalmopathy may involve cytotoxic lymphocytes (T cells) and cytotoxic antibodies to an antigen common to orbital fibroblasts, orbital muscle and thyroid tissue. It is postulated that cytokines released from these sensitized lymphocytes cause inflammation of orbital tissues resulting in the proptosis, diplopia, and edema. For unknown reasons, Graves' ophthalmopathy is worse in smokers and may be exacerbated by radioiodine therapy.
• The skin is warm, sweaty, and velvety in texture. Hyperpigmentation can be seen on the lower extremity, most strikingly on the shins, the backs of the feet, and the nail beds. The hyperpigmentation is due to basal melanosis and heavy deposition of hemosiderin around the dermal capillaries and sweat glands. Its distribution, hemosiderin deposition, and poor response to treatment distinguishes it from the hyperpigmentation seen with Addison's disease. There may be onycholysis (retraction of the nail from the nail plate). In Graves' disease, the pretibial skin may become thickened, resembling an orange peel (pretibial myxedema or thyrotoxic dermopathy). The dermopathy is usually a late manifestation of the disease, and affected patients invariably have ophthalmopathy. The most common form of the dermopathy is non-pitting edema, but nodular, plaque-like, and even polypoid forms also occur. The pathogenesis of thyroid dermopathy may also involve the lymphocyte cytokine stimulation of fibroblasts. Thyroid dermopathy is associated with a very high serum titer of TSH-R antibodies.^[4]

Hashimoto's thyroiditis is the most common cause of myxodema in the United States^[5]. In third world countries iodine deficiency is a significant contributor to hypothyroidism.

See also

• Thyroid hormone

References