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Pathophysiology
Clinical meaning
Myxedema coma is the most severe, life-threatening manifestation of decompensated hypothyroidism. Severe thyroid hormone deficiency reduces cellular metabolism throughout the body: decreased Na+/K+-ATPase activity, reduced oxygen consumption, impaired thermogenesis, and slowed protein synthesis. Cardiovascular effects include bradycardia, decreased cardiac output, reduced stroke volume, and pericardial effusion (accumulation of glycosaminoglycans and fluid). Respiratory failure occurs from central hypoventilation (blunted CO2 response), respiratory muscle weakness, and pleural effusions. CNS effects include decreased cerebral blood flow, altered mental status progressing to coma, and seizures. Hypothermia results from impaired thermogenesis. Hyponatremia from impaired free water excretion (reduced GFR, increased ADH) is common and may be severe. The term 'myxedema coma' is somewhat misleading — most patients present with altered mental status rather than frank coma, and the 'myxedema' refers to the characteristic non-pitting edema from glycosaminoglycan accumulation in the dermis.
Diagnostics & workup:
- TSH: markedly elevated in primary hypothyroidism (most common); low/normal in secondary (pituitary) hypothyroidism
- Free T4: extremely low; free T3 may also be low but T4 is more reliable in acute illness
- Clinical diagnosis: altered mental status + hypothermia + precipitating event in context of hypothyroidism — DO NOT delay treatment for lab confirmation
- ABG: respiratory acidosis (hypercapnia from hypoventilation), hypoxemia
- BMP: hyponatremia (common and potentially severe), hypoglycemia (reduced gluconeogenesis, concurrent adrenal insufficiency)
- CBC: anemia (normocytic), possible leukocytosis if infection is precipitant
- CK: may be markedly elevated (hypothyroid myopathy, rhabdomyolysis)
- Cortisol: must assess for concurrent adrenal insufficiency (autoimmune polyendocrine syndrome; also, treating with thyroid hormone without cortisol replacement in a patient with concurrent adrenal insufficiency can precipitate adrenal crisis — thyroid hormone increases cortisol metabolism)
Risk factors:
- Elderly women with longstanding untreated or undertreated hypothyroidism
- Cold weather exposure (inability to thermoregulate — most common precipitant is winter season)
- Infection, sepsis (precipitant in 30-50%)
- Non-adherence to levothyroxine therapy
- Medications: sedatives, opioids, anesthetics, lithium, amiodarone (all can precipitate myxedema coma in hypothyroid patients)
- Recent surgery, trauma, or critical illness
- Heart failure, stroke, GI bleeding (any acute illness in severely hypothyroid patient)
- Prior thyroidectomy or radioactive iodine therapy without adequate replacement
Management
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Prescribing & monitoring
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Takeaways
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