DESCRIPTION

• Decreased level of effective circulating thyroid hormone leads to decreased metabolic rate and decreased sensitivity to catecholamines.
• More common in woman and the elderly
• Myxedema coma is a rare, extreme form of hypothyroidism characterized by altered mental status and defective thermoregulation triggered by a precipitating event in a patient with hypothyroidism.

ETIOLOGY

• Primary:
  • Idiopathic
  • Congenital
  • Autoimmune:
    • Thyroiditis
    • Hashimoto disease
  • Iatrogenic:
    • Postsurgical
    • External radiation
    • Radioiodine therapy
    • Drugs (iodides, lithium, amiodarone, sunitinib, bexarotene, interferons, narcotics, sedatives)
  • Neoplasm: Primary (carcinoma) or secondary (infiltration)
  • Infection: Viral (rarely aerobic or anaerobic bacteria)
  • Iodine deficiency (most common cause worldwide)
• Central (very rare):
  • Pituitary or hypothalamic disorder induced by drugs or severe illness
  • May have other associated hormone deficiencies
• Myxedema coma:
  • Critical decompensation of a patient with hypothyroidism due to a stress, often during winter months. Stressors include:
    • Infection
    • Hypothermia
    • Intoxication
    • Drugs
    • Cerebrovascular accident
    • Heart failure
    • Trauma

Pregnancy Considerations

• Hypothyroid women require increased exogenous thyroid hormone replacement during pregnancy above baseline
• Postpartum thyroiditis occurs in up to 10% of women:
  • Usually 3–6 mo postpartum
  • Typically resolves without treatment

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

History

• Exhaustion
• Cold intolerance
• Headaches
• Diminished hearing
• Myalgias and muscle weakness
• Menorrhagia
• Infertility
• Carpal tunnel syndrome
• Constipation
• Weight gain
• Depression, hallucinations, or paranoia
• Cognitive impairment

Physical Exam

• Periorbital edema
• Sparse, coarse hair and brittle nails
• Absent lateral 1/3 of eyebrows (Queen Anne sign)
• Husky or hoarse voice
• Goiter
• Prolonged relaxation phase of deep tendon reflexes (DTRs)
• Yellow, dry, pale, cool, coarse skin
• Myxedema (dry, waxy swelling of skin)
• Nonpitting edema of hands and feet
• Myxedema coma:
  • Altered mental status
  • Hypotension
  • Hypothermia
  • Respiratory failure
  • Bradycardia

Pediatric Considerations

• Undiagnosed hypothyroidism in infants has largely been eliminated via universal screening at birth
• Hypothyroidism in childhood is usually due to Hashimoto disease.
• Children may manifest with retardation of mental developmental, linear growth, and sexual maturation

Geriatric Considerations

Typical symptoms of hypothyroidism may be confused with changes associated with aging.

ESSENTIAL WORKUP

Lab confirmation of the diagnosis of hypothyroidism/myxedema coma may not be available in the ED, and therapy should be initiated based on clinical suspicion.

DIAGNOSIS TESTS & INTERPRETATION

Search for the underlying cause of myxedema coma.

Lab

• Thyroid function studies:
  • Low total and free thyroxine (T₄)
  • Low total and free triiodothyronine (T₃)
  • Thyroid stimulating hormone (TSH):
    • Increased in primary hypothyroidism but normal or decreased in central pathology
• Anemia
• Hyponatremia
• Hypoglycemia
• Hypoxemia
• Hypercapnia
• Respiratory acidosis
• Elevated lactate dehydrogenase (LDH), creatine kinase (CK), cholesterol, creatinine

Imaging

CXR:

• Enlarged cardiac silhouette due to pericardial effusion

Diagnostic Procedures/Surgery

ECG:

• Sinus bradycardia, low voltage, PR interval prolongation, bundle branch blocks, QT interval prolongation and nonspecific ST–T-wave changes
• May see Osborn wave if profoundly hypothermic

DIFFERENTIAL DIAGNOSIS

• Chronic nephritis
• Chronic renal disease
• Heart failure
• Depression
• Hypoalbuminemia
• Pernicious anemia
• Nephrotic syndrome
• Sepsis

ALERT

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

• ABCs:
  • Intubation and ventilation may be necessary
• Cardiac monitor
• Blood pressure support
• Supplemental oxygen to meet metabolic needs
• Correct hypothermia:
  • Initiate passive warming measures
  • Aggressive rewarming may precipitate hypotension from vasodilation

ED TREATMENT/PROCEDURES

• Mild hypothyroidism:
  • Refer for oral thyroid hormone replacement as an outpatient
• Myxedema coma:
  • Life-threatening condition
  • Initiate thyroid hormone replacement therapy if a high index of suspicion:
    • Prompt IV replacement improves survival
    • Controversy over regimen exists
    • Thyroxine (T₄) and triiodothyronine (T₃)
    • Reassess 4 hr after initial dose
    • Use smaller doses of T₄ and avoid T₃ in the elderly or patients with cardiac disease to avoid precipitating ischemia
  • Hydrocortisone to prevent Addisonian crisis
  • Dextrose for hypoglycemia
  • IV fluid bolus for hypotension:
    • Avoid pressors if possible, may precipitate dysrhythmias
    • Response to pressors is poor until thyroid replacement initiated
    • Thyroid hormone augments pressors
  • Consider hypertonic saline for severe hyponatremia
  • Correct the underlying precipitant

MEDICATION

First Line

Thyroid hormone therapy:

• Administer T₄, T₃, or a combination:
  • Combination therapy:
    • Thyroxine (T₄): 2 µg/kg (ideal body mass) load IV followed by 10–40 µg IV/PO daily
    • PLUS
    • Triiodothyronine (T₃): 10 µg load IV followed by 10 µg IV q8–12h until able to tolerate PO T₄
  • Thyroxine (T₄): 10–40 µg IV or IM daily
  • Triiodothyronine (T₃): 10–20 µg load IV followed by 10 µg IV q4h for 24 hr, then 10 µg IV q6h for 24–48 hr

Second Line

• Hydrocortisone: 100 mg (peds: 4 mg/kg/24h) IV q6–8h
• Dextrose: 50–100 mL D₅₀ (peds: 5 mL/kg of D₁₀) IV

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

All patients with myxedema coma require ICU admission.

Discharge Criteria

Hypothyroidism is managed in the outpatient setting.

Issues for Referral

• Primary care providers can generally manage hypothyroidism.
• Pregnant patients, elderly patients, and those with ischemic heart disease require special consideration when initiating thyroid hormone replacement.

FOLLOW-UP RECOMMENDATIONS

• Patients should be referred to a primary care provider for initiation of oral thyroid hormone replacement therapy.
• Severe untreated maternal hypothyroidism can negatively impact fetal brain development and cause obstetrical complications.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Signs and symptoms of hypothyroidism are nonspecific and may be confused with other mental or physical disorders.
• Response to treatment for hypothyroidism may take weeks and is best initiated by the primary care physician.
• Consider myxedema coma in patients with altered mental status and underlying hypothyroidism.
• Myxedema coma has a high mortality rate and requires aggressive treatment. However, avoid parenteral T₃ in cardiac and elderly patients.

ICD9

• 243 Congenital hypothyroidism
• 244.8 Other specified acquired hypothyroidism
• 244.9 Unspecified acquired hypothyroidism

ICD10

• E03.1 Congenital hypothyroidism without goiter
• E03.5 Myxedema coma
• E03.9 Hypothyroidism, unspecified

[Outline]

• ICD9
• ICD10

• Brent GA, Davies TF. Hypothyroidism and thyroiditis. In: Melmed S, Polonsky KS, Larsen PR, et al. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Saunders Elsevier; 2011:Chapter 13.
• Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012;96(2):385–403.
• Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: A new look into an old crisis. J Thyroid Res. 2011;2011:493462.
• Vaidya B, Pearce SH. Management of hypothyroidism in adults. BMJ. 2008;337:a801.

See Also (Topic, Algorithm, Electronic Media Element)

Hyperthyroidism

Rita K. Cydulka

Tammy L. Weiner