Myxedema: Definition and Clinical Significance
Myxedema is a condition characterized by deposition of mucopolysaccharides in the dermis causing non-pitting edema, typically associated with severe hypothyroidism, though it can also present in certain hyperthyroid states. 1
Types of Myxedema
Generalized myxedema: The classic cutaneous manifestation of hypothyroidism caused by deposition of dermal acid mucopolysaccharides, notably hyaluronic acid, resulting in thickened skin that does not pit with pressure 1
Localized myxedema (pretibial myxedema): An autoimmune manifestation primarily seen in Graves' disease and occasionally in Hashimoto's thyroiditis, characterized by localized skin lesions typically on the pretibial area 2
Myxedema coma: A life-threatening emergency characterized by poor circulation, hypometabolism, and severe decompensated hypothyroidism with a high mortality rate 3, 4
Clinical Presentation
Generalized Myxedema (Hypothyroid-Associated)
- Presents with thickened, waxy skin that does not pit with pressure 1
- Associated with other hypothyroid symptoms including fatigue, weight gain, constipation, and cold intolerance 5
- Can progress to myxedema coma in severe cases if left untreated 3
Localized/Pretibial Myxedema
- Usually asymptomatic skin lesions with primarily cosmetic significance 2
- Almost always associated with relatively severe ophthalmopathy in Graves' disease 2
- High serum concentrations of thyroid-stimulating hormone receptor antibodies 2
- Localization in pretibial area relates to mechanical factors and dependent position 2
Myxedema Coma
- Extreme manifestation of hypothyroidism with altered mental status 5
- Precipitated by infections, discontinuation of thyroid supplements, or other stressors 3
- Features include hypothermia, hypoventilation, hypotension, hyponatremia, and decreased consciousness 3
- Requires immediate intensive care management 4
Pathophysiology
In hypothyroidism: Decreased thyroid hormone leads to increased deposition of glycosaminoglycans (particularly hyaluronic acid) in the dermis 1
In hyperthyroidism (paradoxical myxedema): Recent research suggests a hormetic response to thyroid hormones, with both extremely low and extremely high thyroid hormone levels potentially causing myxedema through different mechanisms 6
In pretibial myxedema: Both humoral and cellular immune mechanisms stimulate fibroblasts to produce excessive glycosaminoglycans 2
Diagnosis
- Clinical presentation of characteristic skin changes 1, 2
- History of thyroid dysfunction (either hypothyroidism or Graves' disease) 2
- Laboratory confirmation of thyroid dysfunction (TSH, T4 levels) 7
- Skin biopsy may be required in some cases of pretibial myxedema 2
Treatment
For Generalized Myxedema (Hypothyroidism)
- Thyroid hormone replacement with levothyroxine 8
- Careful dosing in elderly patients or those with cardiovascular disease (starting with 25-50 μg daily) 4
- Monitor for potential complications including cardiac arrhythmias 8
For Myxedema Coma
- Immediate hospitalization in intensive care unit 4
- Intravenous thyroid hormone replacement (oral administration not recommended due to unpredictable absorption) 8
- Glucocorticoid administration (hydrocortisone 100 mg IV every 8 hours) until adrenal insufficiency is ruled out 4
- Supportive care including airway management, ventilation if necessary, and correction of hypoglycemia 4
For Pretibial Myxedema
- Mild cases (50%) achieve complete remission after several years without treatment 2
- Topical corticosteroids under occlusive dressing for symptomatic or cosmetic concerns 2
- Systemic immunomodulation for severe cases, though long-term efficacy is uncertain 2
- Compressive therapy when significant edema is present 2
Complications and Prognosis
- Myxedema coma has high mortality if not promptly treated 3
- Poor prognostic factors include hypotension, bradycardia, need for mechanical ventilation, treatment-resistant hypothermia, sepsis, low GCS, and high APACHE II or SOFA scores 3
- Pretibial myxedema is typically benign but can progress to elephantiasis or thyroid acropachy in advanced forms 2