What is myxedema?

What is Myxedema?

Myxedema is a clinical manifestation of severe thyroid dysfunction characterized by deposition of glycosaminoglycans (particularly hyaluronic acid) in the skin and subcutaneous tissues, occurring in both advanced hypothyroidism and, paradoxically, in hyperthyroidism (Graves' disease).

Two Distinct Forms of Myxedema

Generalized Myxedema (Hypothyroidism)

• Generalized myxedema represents the classic cutaneous manifestation of severe hypothyroidism, caused by dermal deposition of acid mucopolysaccharides, notably hyaluronic acid 1
• The affected skin appears edematous but characteristically does not pit with pressure, distinguishing it from other forms of edema 1
• This condition occurs as part of the spectrum of untreated or inadequately treated hypothyroidism, with symptoms including fatigue, muscle cramps, constipation, cold intolerance, hair loss, voice changes, weight gain, and intellectual slowness 2
• Myxedema coma represents the most severe, life-threatening manifestation of decompensated hypothyroidism, associated with high mortality rates and characterized by cardiogenic shock, respiratory depression, hypothermia, and altered mental status 3

Localized (Pretibial) Myxedema (Hyperthyroidism)

• Pretibial myxedema (also called localized myxedema or thyroid dermopathy) is an autoimmune manifestation occurring in Graves' disease and occasionally in Hashimoto's thyroiditis 4
• This form presents as skin lesions typically in the pretibial area, though it can occur in other locations, indicating a systemic autoimmune process 4
• Nearly all patients with pretibial myxedema have high serum concentrations of thyroid-stimulating hormone receptor antibodies and are associated with relatively severe ophthalmopathy 4
• The lesions are usually asymptomatic with primarily cosmetic concerns, though advanced forms can progress to elephantiasis or thyroid acropachy 4

Pathophysiology

• Both forms involve stimulation of fibroblasts and production of large amounts of glycosaminoglycans, though through different mechanisms 4
• In Graves' disease, thyroid-stimulating hormone receptors in connective tissue serve as the antigen for both humoral and cellular immune mechanisms 4
• The pretibial localization relates to mechanical factors and dependent positioning of the lower extremities 4
• Recent evidence suggests myxedema in both hyper- and hypothyroidism represents a hormetic-type response to thyroid hormones, with bioelectrical impedance analysis showing altered fluid body composition parameters more evident in overt hyperthyroidism than severe hypothyroidism 5

Clinical Recognition

• In hypothyroidism, myxedema appears as part of a constellation of signs including low metabolic rate, weight gain tendency, and somnolence 2
• Diagnosis requires recognizing the characteristic non-pitting edema in the context of thyroid dysfunction 1
• For pretibial myxedema, diagnosis is based on typical pretibial skin lesions in association with a history of Graves' hyperthyroidism and ophthalmopathy; skin biopsy may be needed for confirmation 4
• White blood cell count in pericardial effusions from myxedema is characteristically very low, with high monocyte counts (74 ± 26%) when present 2

Critical Pitfall

Do not confuse myxedema with other causes of peripheral edema such as right heart failure, calcium channel blocker use, lymphedema, hypoalbuminemia, venous obstruction, or infiltrative diseases 2. The key distinguishing feature is the non-pitting nature of myxedema and its association with thyroid dysfunction 1.