Myxedema Coma

Pathophysiology

• Myxedema coma occurs among patients with long-standing, untreated or inadequately treated hypothyroidism when subjected to stress. A precipitating event can be found in most cases of hypothyroidism.
• Poorly controlled hypothyroidism + Acute precipitant Myxedema Coma
• Etiologies of hypothyroidism include primary, secondary, or tertiary causes, acute adrenal insufficiency.
• Primary hypothyroidism (disease of the thyroid gland) accounts for 95% of hypothyroidism. Diseases include Hashimoto’s thyoiditis most commonly, iatrogenic causes (post-radiation, post-surgical, anti-thyroid medications), congenital abnormalities, enzymatic defects, neoplasms, or infections
• Secondary hypothyroidism (disease of the pituitary gland) accounts for 4% of hypothyroidism. Diseases include pituitary tumors, infiltrative diseases (sarcoid), infarction, hemorrhage, or trauma.
• Tertiary hypothyroidism (disease of the hypothalmus) accounts for < 1% of hypothyroidism. Etiologies include injury, infarction, infiltration or hemorrhage.
• Acute precipitants of myxedema coma are diverse. They include infection most commonly, environmental (prolonged cold exposure), cardiac (ischemia, CHF), pulmonary diseases, metabolic disease, trauma, surgery, or medications.
• The incidence is greater in women, the majority are elderly (half are between the ages of 50 and 70).
• Before the advent of thyroid hormone replacement, the mortality rate approached 100%. Even with treatment, the mortality may be as high as 50%.

Diagnosis and Evaluation

• Diagnosis is purely clinical and based on a constellation of signs and symptoms.

Laboratory/Studies

• Thyroid function tests demonstrate an elevated TSH, low total T4 and free T4. There are however no pathognomonic lab values, and these studies may not be available in the Emergency Department time course.
• Complete blood count is standard. A normal WBC count in the setting of infection is expected (left shift and bandemia more sensitive). Anemia of chronic disease can be seen.
• Hypoglycemia is usually mild but can be severe.
• Hyponatremia may be caused by SIADH secondary to hypothyroidism.
• Arterial blood gas may demonstrate hypoxemia, hypercapnia, and/or acidosis.

Signs and symptoms of hypothyroidism/myxedema coma

Hypothyroidism	Hypothyroidism	Myxedema
Symptoms	Signs	Coma
Weakness, fatigue	Prolonged relaxation of DTRs	Exaggerated s/sx of
Cold intolerance	Non-pitting edema (myxedema)	hypothyroidism plus:
Paresthesias	Dry, scaley skin	Hypothermia
Myalgias	Yellow skin	Bradycardia
Menorrhagia	Hypothermia	Hypoventilation
Hearing loss	Sparse pubic and axillary hair	Hypotension
Emotional lability	Thinning eyebrows	Altered mental status/coma
Forgetfulness	Mononeuropathy	Pericardial/pleural/
	Hoarse voice	peritoneal effusions
	Goiter (10% of cases)	Ileus
	Thyroidectomy scar	Acute urinary retention

Non-pitting edema and hoarse voice are due to hyaluronic acid deposition in the dermis and vocal cords, respectively. Yellowing of the skin is caused by decreased conversion of carotene to vitamin A. Mononeuropathies, such as carpal tunnel syndrome, are fairly common.

• Elevated enzymes including CPK, LDH, or LFTs may be present.
• Elevated cholesterol levels are often present
• CXR should be done to check for signs of pneumonia, CHF, or cardiomegaly ( pericardial and pleural effusions in one-third of cases ).
• EKG should be examined for signs of ischemia/infarction, bradycardia, conduction blocks, or low voltage (effusion).
• Head CT may be needed to rule out other explanations for altered mental status.

ED Management

The treatment of myxedema coma can be divided into three components:

1. initial supportive therapy;
2. thyroid hormone replacement; and
3. identification and treatment of precipitating illness.

Supportive Therapy

• Hypoxia and hypoventilation may be life-threatening. Administer supplemental oxygen and consider early intubation if necessary.
• Hypoglycemia needs immediate treatment. Obtain rapid D-stick and administer glucose if necessary.
• Hypotension should be treated with 0.9% NS as necessary for hemodynamic stability with cautious attention to underlying CHF. Pressor agents must be used with caution, as they may precipitate arrhythmias in the setting of myxedema coma. The administration of thyroid hormone will also augment the pressor effect.
• Treat hypothermia with gradual, passive rewarming. Rapid, active rewarming can be harmful.
• Correct hyponatremia gradually with fluid restriction. Hypertonic saline should be considered for Na < 110, worsening mental status, or seizures.
• Avoid the use of sedative/hypnotics that may further depress respiratory, CNS and metabolic function.
• Administer stress doses of corticosteroids. Cortisol levels are low in the hypothyroid patient. Hydrocortisone 100 mg IV q 8 h should be given empirically.

Thyroid Hormone Replacement

• Prompt intravenous replacement of thyroid hormone has been shown to improve the survival of myxedema coma. L-thyroxine (T4) is the drug of choice. It has a more gradual onset with fewer cardiac complications as compared to triiodothyronine (T3). The exact dose is controversial, but usually 300-500 mg IV is given while on a cardiac monitor. This can be followed by 50-100 mg IV daily after admission.

Search for and Treat Precipitant Illness

• A thorough history and physical exam is required, as well as laboratory and radiologic investigation for infection/sepsis, metabolic abnormalities, cardiac, CNS, or renal disease. Treatment should be given as needed.
• All patients with myxedema coma should be admitted to the ICU.