Myxedema
Encyclopedia
Myxedema describes a specific form of cutaneous and dermal edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

 secondary to increased deposition of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...

 components (like glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...

s, hyaluronic acid, and other mucopolysaccharides) in subcutaneous tissue as seen in various forms of hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 and Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

. It is more common in women than in men.

Terminology

The word originates from taken from ancient Greek to convey 'mucus' or 'slimy substance' and for swelling.
  • Hyperthyroid: Myxedema typically presents in specific areas (pretibial myxedema
    Pretibial myxedema
    Pretibial myxedema is an infiltrative dermopathy, resulting as a rare complication of Graves' disease, with an incidence rate of about 1-4% in patients.-Presentation:...

     and exophthalmos
    Exophthalmos
    Exophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral or unilateral . Measurement of the degree of exophthalmos is performed using an exophthalmometer...

    ) and is related to high levels of TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     receptor stimulation and/or inflammation mounted against the TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     receptor itself. Myxedema of the lower legs (called pretibial myxedema
    Pretibial myxedema
    Pretibial myxedema is an infiltrative dermopathy, resulting as a rare complication of Graves' disease, with an incidence rate of about 1-4% in patients.-Presentation:...

    ), can occur in one to four percent of patients with Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

     -- a condition that causes hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

    .

  • Hypothyroid: Myxedema is also used to describe the clinical syndrome secondary to hypothyroidism
    Hypothyroidism
    Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

    . Symptoms can include depression, mental slowness, weakness, bradycardia, fatigue, hypothermia
    Hypothermia
    Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...

    , alopecia
    Alopecia
    Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

    , and many others (see symptoms of severe hypothyroidism). Used in this way, myxedema can be considered the adult counterpart of cretinism
    Cretinism
    Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...

    .


Myxedema coma is rare and establishing the diagnosis requires a high index of suspicion. Myxedema coma represents the severest form of hypothyroidism and has an associated mortality rate of 30 percent to 40 percent. It can occur due to long-standing, untreated hypothyroidism, but is often linked to a precipitant, such as acute infection, myocardial infarction, congestive heart failure, cerebral vascular accident, trauma, or drug toxicity. Several medications can cause hypothyroidism, and patients taking them must be carefully monitored. These medications include amiodarone, lithium, and sedatives. No consensus exists on specific thyroid hormone replacement regimens for myxedema coma. Most experts agree that a large intravenous bolus of levothyroxine should be administered (200 to 400 mcg), followed by daily doses of 50 to 100 mcg, based on the patient's weight and comorbidities. Other experts advocate the use of triiodothyronine (T3) or a combination of both T3 and T4. In addition to thyroid replacement therapy, it is important to detect coexisting adrenal insufficiency and treat patients with stress-dose steroids to avoid precipitating adrenal crisis.

Cause

The increased deposition of glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...

 is not fully understood, however two mechanisms predominate.
  • Exophthalmos in particular results from TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     receptor stimulation on fibroblasts behind the eyes which leads to increased glycosaminoglycan
    Glycosaminoglycan
    Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...

     deposition. It is thought that many cells responsible for forming connective tissue react to increases in TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     levels.
  • Secondarily, in autoimmune thyroid diseases lymphocytes react to the TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     receptor. Thus, in addition to the inflammation within the thyroid, any cell that expresses the TSH
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     receptor will likely experience lymphocytic infiltrates as well. The inflammation can cause tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans.


The increased deposition of glycosaminoglycans causes an osmotic edema and fluid collection.

Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

is the most common cause of myxedema in the United States.
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