Author:
Bradley A.Wallace
TerrySinghapricha
Description
- Decreased level of thyroid hormone leads to a variety of clinical manifestations
- More common in women 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
- Postsurgical
- External radiation
- Radioiodine therapy
- Drugs:
- Iodides, lithium, amiodarone, sunitinib, bexarotene, interferons, narcotics, sedatives
- Phenytoin and carbamazepine increase clearance of T4 in patients with hypothyroidism taking T4
- 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:
- Life-threatening decompensation of a patient with hypothyroidism due to a stress, often during winter months
- Stressors include:
- Infection
- Hypothermia
- Intoxication
- Drugs (e.g., opioids)
- Cerebrovascular accident
- Heart failure
- Trauma
Pregnancy Prophylaxis |
- Hypothyroidism has been associated with preterm delivery, placental abruption, preeclampsia, low birth weight, and increased rate of Caesarean section
- 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
|
Signs and Symptoms
History
- Exhaustion
- Cold intolerance
- Headaches
- Diminished hearing
- Myalgias and muscle weakness
- Dyspnea on exertion
- Decreased exercise tolerance
- 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
- Macroglossia
- Goiter
- Prolonged relaxation phase of deep tendon reflexes (DTRs)
- Yellow, dry, pale, cool, coarse skin
- Myxedema (dry, waxy swelling of skin)
- Nonpitting edema of hand s 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 most commonly 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
Evaluate for precipitating etiologies. An initial lab draw should include: TSH and free T4. 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
Diagnostic 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 hypothyroidism
- Anemia
- Hyponatremia
- Hypoglycemia
- Hypoxemia
- Hypercapnia
- Respiratory acidosis
- Elevated lactate dehydrogenase (LDH), creatine kinase (CK), cholesterol, creatinine
- Hyperlipidemia
Imaging
CXR:
- Enlarged cardiac silhouette due to pericardial effusion
Diagnostic Procedures/Surgery
ECG:
- Sinus bradycardia, low voltage, PR interval prolongation, bundle branch blocks, PVCs, QT interval prolongation and nonspecific ST-T-wave changes
- May see an Osborn wave if profoundly hypothermic
Differential Diagnosis
- Chronic nephritis
- Chronic renal disease
- Heart failure
- Depression
- Hypoalbuminemia
- Pernicious anemia
- Nephrotic syndrome
- Sepsis
ALERT |
- Euthyroid sick syndrome:
- Illness, surgery, fasting may produce abnormal thyroid function test results
- Thyroid function tests performed during acute nonthyroid illness may be abnormal and should be interpreted with caution
|
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
- T4 and T3
- Reassess 4 hr after initial dose
- In elderly patients or patients with cardiac disease, use smaller doses of T4 and consider avoiding T3 to avoid precipitating cardiac ischemia
- Intravenous glucocorticoids (until underlying adrenal insufficiency has been ruled out)
- Dextrose for hypoglycemia
- IV fluid bolus for hypotension:
- Avoid pressors if possible as they 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 precipitating factor(s)
Medication
First Line
In myxedema coma, administer T4, T3, or a combination:
- Initial combination therapy:
- Doses on lower end of this range should be used in elderly patients or patients with a history of coronary artery disease or cardiac arrhythmia
- If no significant clinical response in 6-12 hr, a repeat dose may be given to bring total dose to 400 mcg in first 24 hr
- PLUS
- Subsequent therapy:
- T4: 1.6 mcg/kg daily (may give 75% of this dose if giving IV)
- T3: 2.5-10 mcg IV q8h, with lower doses in this range reserved for elderly patients or patients with a history of CAD or arrhythmia
Second Line
- Hydrocortisone: 100 mg (peds: 4 mg/kg/24 hr) IV q6-8h to treat undiagnosed concomitant adrenal insufficiency until ruled out
- Dextrose: 50-100 mL D50 (peds: 5 mL/kg of D10) IV for hypoglycemia
- Consider empiric antibiotics until an infectious etiology has been ruled out
Disposition
Admission Criteria
All patients with myxedema coma require ICU admission
Discharge Criteria
Hypothyroidism with stable vital signs and without myxedema coma is managed in the outpatient setting
Issues for Referral
- Primary care providers can generally manage hypothyroidism
- Pregnant patients, pediatric 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 obstetric complications
- BrentGA, DaviesTF. Hypothyroidism and thyroiditis. In: MelmedS, PolonskyKS, LarsenPR, et al. Williams Textbook of Endocrinology. 12th ed.Philadelphia, PA: Saunders Elsevier; 2011: Chapter 13.
- JonklaasJ, BiancoAC, BauerAJ, et al. Guidelines for the treatment of hypothyroidism: Prepared by the American Thyroid Association Task Force on thyroid hormone replacement . Thyroid. 2014;24(12):1670-1751.
- Klubo-GwiezdzinskaJ, WartofskyL. Thyroid emergencies . Med Clin North Am. 2012;96(2):385-403.
- MathewV, MisgarRA, GhoshS, et al. Myxedema coma: A new look into an old crisis . J Thyroid Res. 2011;2011:493462.
See Also (Topic, Algorithm, Electronic Media Element)
Hyperthyroidism
The authors gratefully acknowledge Rita K. Cydulka and Tammy L. Weitner for their contribution to the previous edition of this chapter.