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MyxedemaEdit

Myxedema is a term historically used to describe the special kind of non-pitting edema and mucopolysaccharide-rich tissue changes that occur in severe hypothyroidism. While the word is still encountered in clinical practice, modern medicine usually frames the condition within the broader spectrum of hypothyroidism and its complications, with myxedema most notably associated with the life-threatening state called myxedema coma if not promptly treated. The condition highlights how thyroid hormone deficiency can ripple through multiple organ systems, from skin and metabolism to cardiac function and mental status.

Pathophysiology

  • Thyroid hormones regulate metabolic rate and the turnover of many body tissues. When production or action of these hormones is insufficient, metabolism slows and glycosaminoglycans accumulate in interstitial spaces, leading to the characteristic edema and thickened skin texture described as myxedematous change.
  • The edema of myxedema is non-pitting and can involve the face, hands, and around the eyes, and it reflects altered extracellular matrix components as well as reduced lymphatic drainage in the setting of hypothyroidism.
  • Systemic effects include slowed cardiovascular function, reduced thermogenesis, fatigue, cognitive slowing, and lipid abnormalities. The full clinical picture depends on the duration and severity of thyroid hormone deficiency.
  • Myxedema coma represents a critical end of the spectrum: a rare but life-threatening emergency that requires rapid recognition and treatment with thyroid hormone replacement, supportive care, and management of precipitating factors such as infection or drug effects.

Etiology

  • Autoimmune thyroiditis, particularly Hashimoto's thyroiditis, is the most common cause of hypothyroidism in many populations, and it frequently underlies myxedematous changes when the disease progresses.
  • Iodine deficiency remains a major cause in parts of the world where iodine intake is inadequate.
  • Iatrogenic causes include thyroidectomy (surgical removal of the gland) or thyroid radiation, which can reduce thyroid hormone production.
  • Drug-induced hypothyroidism can occur with medications such as lithium, amiodarone, or certain anti-thyroid drugs, contributing to myxedematous manifestations in susceptible individuals.
  • Less common etiologies include congenital hypothyroidism, infiltrative diseases, or pituitary dysfunction that reduces stimulation of the thyroid gland.

Clinical features

  • Symptoms of hypothyroidism typically include fatigue, cold intolerance, weight gain, dry skin, hair thinning, constipation, and generalized weakness.
  • The myxedematous component adds non-pitting edema of the skin and mucous membranes, sometimes causing facial puffiness and periorbital swelling.
  • There may be slowed movements, slowed speech, depression or cognitive impairment, and reduced heart rate. In elderly patients, presentations can be atypical, with confusion or somnolence rather than classic symptoms.
  • When untreated or inadequately treated, hypothyroidism can progress to myxedema coma, characterized by severe hypothermia, hypotension, hypoventilation, and altered mental status, requiring urgent medical intervention.

Diagnosis

  • Laboratory evaluation centers on thyroid function tests. Primary hypothyroidism typically shows low free thyroxine (free T4) with elevated thyroid-stimulating hormone (TSH). In central (pituitary or hypothalamic) hypothyroidism, TSH may be low or inappropriately normal with low free T4.
  • Autoimmune markers such as anti-thyroid peroxidase (anti-TPO) antibodies or anti-thyroglobulin antibodies can support an autoimmune etiology like Hashimoto's thyroiditis.
  • Additional tests may reveal hyperlipidemia, hyponatremia, or elevated creatine kinase, which can accompany hypothyroidism.
  • Imaging, such as thyroid ultrasound, may be used in select cases to evaluate glandular structure but is not required for diagnosis.
  • When assessing severity or risk of progression to myxedema coma, clinicians evaluate clinical status, temperature, heart rate, respiratory function, and electrolyte balance.

Treatment

  • The cornerstone of therapy is thyroid hormone replacement, most commonly with levothyroxine. Dosing is individualized based on age, cardiac status, body mass, and comorbidities, with slow titration to achieve normal TSH and free T4 levels.
  • In elderly patients or those with known cardiac disease, starting with a low dose and gradual uptitration reduces the risk of precipitating arrhythmias or heart failure.
  • In suspected myxedema coma, treatment is emergent and typically includes intravenous levothyroxine, careful airway and hemodynamic support, and often adjunctive hydrocortisone until adrenal insufficiency is ruled out.
  • Addressing precipitating factors, such as infection or nonadherence, is essential for successful recovery. Patients with autoimmune thyroiditis may require ongoing, long-term maintenance therapy.

Prognosis and monitoring

  • With appropriate thyroid hormone replacement, symptoms of hypothyroidism often improve over weeks to months, and edema typically resolves as metabolic processes normalize.
  • Regular monitoring of TSH and free T4 helps guide dosing adjustments and ensures maintenance within target ranges.
  • Prognosis depends on factors such as age, comorbidities, and timely initiation of treatment; untreated severe hypothyroidism or myxedema coma carries significant mortality risk.

History

  • The term myxedema reflects earlier clinical descriptions of the mucinous, waxy edema seen in severe hypothyroid states. The understanding of thyroid biology and hormone replacement therapy evolved in the 20th century, transforming a condition once deemed progressive and untreatable into a highly treatable disorder with appropriate management.

See also