Myxedema Coma

Comatose
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Diagnosis and reasoning

A wide variety of conditions may give rise to coma and stupor in the elderly. However, in practice, the most common etiologies are traumatic brain injury, strokes, central nervous system (CNS) infections, metabolic derangements and drug overdoses or intoxication. This patient has no history of trauma, while the normal CT brain makes a stroke less likely. CNS infections are a possibility, especially since the elderly may not manifest fever or typical signs of meningism. However, the normal c-reactive protein (CRP) and full blood count make this diagnosis less likely. Drug overdose or intoxication is also less likely given the long duration of symptoms and unremarkable medical history. Metabolic causes are highly likely, with electrolyte disturbances (hyponatremia), hepatic encephalopathy and uremic encephalopathy being common diagnoses to consider. However, there are no clinical features suggestive of liver or renal failure. The presence of hypothermia is an important clinical finding and should raise suspicion of an endocrine cause such as myxedema coma. This diagnosis is supported by the presence of bradycardia and slow relaxing ankle jerks, as well as by the sinus bradycardia and low voltage complexes in the ECG. Serum electrolyte estimation reveals the presence of hyponatremia, which is a common finding in myxedema coma. Note that while hyponatremia itself may cause altered mentation, a level of 125 mEq/l is unlikely to cause this degree of impairment. The thyroid function tests demonstrate very high thyroid stimulating hormone (TSH) levels and undetectable free thyroxine (T4) and triiodothyronine (T3) levels. This is indicative of severe primary hypothyroidism and confirms the presence of myxedema coma. Severe hypothyroidism alone rarely causes myxedema coma - there is usually an additional precipitating cause (such as infections). Further evaluation in this regard shows that this lady has an urinary tract infection (UTI). As respiratory compromise is also common, arterial blood gas analysis (ABG) is important. This lady's ABG shows evidence of CO2 retention and impending type II respiratory failure. IV Thyroxine supplementation is the cornerstone of her management, while the UTI should be treated with IV antibiotics. Intubation and ventilation is important in view of the respiratory failure and also to protect the airway. There is no role for IV adrenaline in her current management.


Discussion

Myxedema coma is a rare, life-threatening manifestation of severe decompensated hypothyroidism. Note that the term "coma" is a misnomer, as most patients present with an altered mental state rather than frank coma. The exact incidence is controversial, although the condition is becoming increasingly rare due to early detection of hypothyroidism. The patients affected are predominantly female and elderly. In normal individuals, the hormones secreted by the thyroid gland play a key role in regulating the basal metabolic rate. The heat thus generated is important in maintaining the core temperature of the body. In patients with longstanding hypothyroidism, there is a marked decrease in basal metabolism and thus in heat generation. However, a stable core temperature is maintained via a variety of physiological adaptations such as peripheral vasoconstriction, decreased sweating and a reduction in blood volume, heart rate and cardiac output. However, these homeostatic mechanisms may be disrupted by conditions such as hypovolemia (due to GI bleeding, dehydration or diuretic use), cardiac decompensation (due to heart failure or myocardial infarction), central nervous system dysfunction (due to strokes or sedative use), an exaggerated stress response (to infections or trauma), or low external environmental temperatures. Disruption results in decompensated hypothyroidism, where vital functions cannot be restored by homeostatic mechanisms alone. This may culminate in myxedema coma. The main features of myxedema coma are an altered mental state (ranging from extreme lethargy to disorientation to frank coma) and hypothermia (or absence of fever in spite of severe infection). As mentioned above, most patients also have an underlying precipitating condition. Important cardiovascular manifestations include bradycardia and hypotension (secondary to diminished cardiac contractility). Pericardial effusions may also occur (due to increased capillary permeability). There may be some degree of respiratory muscle dysfunction and a reduction in respiratory drive, manifesting as hypoventilation and a slow respiratory rate. In addition, pleural effusions may occur. Intestinal motility may also be compromised, leading to gastric atony, paralytic ileus or megacolon. Most patients also manifest physical signs of hypothyroidism (such as dry skin, sparse hair, macroglossia and nonpitting edema) - although these may be absent in the elderly. Typically, the free T3 and T4 levels are low or undetectable in this patients. TSH levels may be highly elevated in patients with primary hypothyroidism, or may be low in patients with central hypothyroidism or severe illness. In patients with low TSH levels, ACTH production may also be compromised, leading to hypoadrenalism. Characteristic biochemical abnormalities include hyponatremia (due to excess vasopressin secretion), renal impairment (due to reduced renal perfusion), and elevation of the muscle fraction of creatine kinase (due to increased membrane permeability). Hypoglycemia is also common. A full blood count may show normocytic or macrocytic anemia. A neutrophilila or a left-shift may be the only marker of infection. ECGs typically show low voltage complexes and/or sinus bradycardia. Non-specific T wave changes and prolongation of the QT interval are also common. The principles of management are rapid institution of thyroid hormone replacement, treatment of the precipitating cause, and close supportive care and monitoring. Thyroid hormone supplementation should be commenced upon clinical suspicion. As gut absorption and motility is usually reduced, most clinicians prefer parenteral thyroid hormone therapy. However, the exact dosages are a matter of controversy, as is whether to administer T4 alone, T4 and T3 together, or T3 alone. Note also that thyroid hormone supplementation may unmask ischemic heart disease (especially in the elderly). In addition, given the possibility of concomitant adrenal insufficiency, cortisol therapy should be considered in these patients. Precipitating causes should be actively screened for and treated as appropriate. If no obvious cause is present, broad spectrum antibiotic therapy should still be considered, as occult infection is common. All patients require close monitoring in an intensive care setting, as cardiac arrhythmias are common during resuscitation. Hyponatremia should be treated via fluid restriction, while IV glucose may be required if hypoglycemia is present. Careful and slow warming is mandatory for treatment of hypothermia. If respiratory failure is noted, intubation and ventilation should be performed. Even with prompt detection and treatment, the mortality rate ranges from 25% to 60%. Features indicative of a poor prognosis include severe hypothermia at presentation, persistent hypothermia despite treatment, bradycardia, hypotension, advanced age, and the presence of sepsis or myocardial infarction.


Take home messages

  1. Myxedema coma is a life-threatening illness and may be the first presentation of hypothyroidism.
  2. Characteristic features include hypothermia and altered mentation. Most patients also have an underlying precipitating illness
  3. Treatment should be commenced upon clinical suspicion - do not delay until thyroid function tests are available.
  4. Many patients have a degree of concomitant hypoadrenalism. Empirical cortisol therapy should be considered.
  5. Cardiac arrhythmias and respiratory failure are common. Thus monitoring and treatment in an intensive care setting is essential.

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  1. Critical Care : Predictors of outcome in myxoedema coma (2008)
  2. Journal of Thyroid Research : Myxedema Coma: A New Look into an Old Crisis (2011)
  3. Postgraduate Medical Journal : Diabetic and endocrine emergencies (2007)
  4. Postgraduate Medical Journal : Endocrine emergencies (2004)
  5. Reviews in Endocrine & Metabolic Disorders : Myxedema coma (2003)