Hypothyroidism is a clinical syndrome in which the deficiency or absence of thyroid hormone slows bodily metabolic processes. Symptoms can manifest in all organ systems and range in severity based on the degree of hormone deficiency. The disease typically progresses over months to years but can occur quickly following cessation of thyroid replacement medication or surgical removal of the thyroid gland.
The term myxedema refers to the thickened, nonpitting edematous changes to the soft tissues of patients in a markedly hypothyroid state. Myxedema coma, a rare, life-threatening condition, occurs late in the progression of hypothyroidism. The condition is seen typically in elderly women and is often precipitated by infection, medication, environmental exposure, or other metabolic-related stresses. Because rapid confirmatory laboratory tests are often unavailable, the diagnosis may be made on clinical grounds with treatment started promptly.[1]
Treatment of myxedema coma requires potentially toxic doses of thyroid hormone, and mortality rates exceeding 20% have been reported even with optimum therapy.[2, 3]
For more information, see Medscape's Hypothyroidism Resource Center.
Signs and symptoms of hypothyroidism
The signs and symptoms characteristic of hypothyroidism are numerous yet often vague and subtle, especially in the early stages of the disease. Note the following:
Lethargy
Generalized weakness
Brittle or thinning hair
Menstrual irregularity
Menorrhagia
Forgetfulness
Fullness in throat
Deep, husky voice secondary to mucopolysaccharide infiltration of the vocal cords
Cold intolerance
Weight gain/difficulty losing weight
Muscle/joint pain or weakness
Inability to concentrate
Headaches
Constipation
Emotional lability
Depression
Blurred vision
Dry hair
Potential physical examination findings include the following:
Pseudomyotonic reflexes - Prolonged relaxation phase, usually at least twice as long as the contraction phase
Hypothermia (especially in myxedema coma)
Skin changes - Dry, cool, coarse, and thickened with a yellowish appearance
Subcutaneous tissues - Nonpitting, waxy, dry edema secondary to accumulation of polysaccharides
Loss of axillary and pubic hair
Pallor
Loss of outer one third of eyebrows
Abdominal distention
Goiter
Unsteady gait/ataxia
Pericardial effusion
Dull facial expression
Coarsening or huskiness of voice
Periorbital edema
Bradycardia, narrow pulse pressure
Macroglossia
Thyroidectomy scar - In patients with altered mental status, suggests myxedema coma as a potential cause
Workup in hypothyroidism
The following measurements and studies are indicated in hypothyroidism[4] :
Electrolytes
Arterial blood gas (ABG)
Urinalysis
Secondary studies include thyroid function studies, thyroid-stimulating hormone (TSH) levels, free thyroxine (T4) levels, triiodothyronine (T3) resin uptake, free T4 index
Imaging studies include chest radiography, an acute abdominal series, head computed tomography (CT) scanning, and echocardiography.
Management
Patients with myxedema coma may present in extremis; implement initial resuscitative measures, including intravenous (IV) access, cardiac monitoring, and oxygen therapy, as indicated. Mechanical ventilation is indicated for patients with diminished respiratory drive or obtundation.
Evaluate for life-threatening causes of altered mental status (eg, bedside glucose, pulse oximetry).
If myxedema coma is suspected on clinical impression, start IV thyroid hormone treatment. With a diagnosis of myxedema coma, initiate hormonal therapy.
Myxedema coma may lead to profound hemodynamic instability and airway compromise. Emergency physicians should anticipate a potentially difficult airway in patients with myxedema coma.[5]
Treat respiratory failure with appropriate ventilatory support. The condition often requires mechanical ventilation.
Avoid medications such as sedatives, narcotics, and anesthetics. Metabolism of these agents may be slowed significantly, causing prolonged effects.
Thyroid hormone is secreted in response to stimulation of the thyroid gland by thyroid-stimulating hormone (TSH) from the anterior pituitary gland. TSH is released through the action of thyrotropin-releasing hormone (TRH) from the hypothalamus.
Hypothyroidism can be caused by permanent loss or atrophy of functional thyroid tissue (primary hypothyroidism); insufficient stimulation of a normal thyroid gland as a result of hypothalamic or pituitary disease (secondary hypothyroidism, often accompanied by compensatory thyroid gland enlargement); or a defect in the TSH molecule (control hypothyroidism).
Primary hypothyroidism accounts for approximately 90-95% of hypothyroidism, with a predominantly autoimmune-mediated etiology. TSH hypersecretion produces excessive thyroid tissue, resulting in goiter formation. Surgical and radiation ablation account for a large percentage of acquired cases of hypothyroidism. Congenital abnormalities, malignancies, and infiltrative disorders including amyloidosis and sarcoidosis can also lead to the disease. Iodine deficiency is rarely responsible for hypothyroidism in developed countries; however, it remains the primary cause worldwide.
Suprathyroidal disorders including hypopituitarism and hypothalamic lesions account for fewer than 10% of cases. Rarely, peripheral resistance to thyroid hormone may occur.
The congenital absence or deficiency of thyroid tissue may result in cretinism, a neurodevelopmental disorder characterized by lethargy, poor peripheral circulation, constipation, and goiter. Because infants are asymptomatic, neonatal screening is vital to prevent permanent sequelae.
Reports on screening surveys for thyroid disease show an incidence of 5.8% for subclinical thyroid abnormalities. However, those with overt signs and symptoms of hypothyroidism likely comprise less than 2% of women and 0.2% of men.
Myxedema coma occurs rarely, appearing in 0.1% of all cases of hypothyroidism.
International
Neonatal screening programs for congenital hypothyroidism show that in many areas around the world hypothyroidism appears in 1 of every 4000 newborns.[6]
In developed countries, the incidence of subclinical hypothyroidism is approximately 8% in women and 3% in men. Endemic goiter usually occurs in environmentally iodine-deficient areas; throughout the world, goiter is estimated to affect 200 million people. Goiter is most common in mountainous areas of the Alps, Himalayas, and Andes, possibly due to low soil iodine content as a result of leaching away of minerals as glaciers melt.
A study by Ono et al estimated the annual incidence of myxedema coma in Japan to be 1.08 per million people.[7]
Race
Anecdotal reports indicate the disease appears more often in white and Hispanic populations.
Sex
Incidence is greater in females than males (female-to-male ratio 5-10:1).
Age
The incidence of primary hypothyroidism increases progressively with age, typically at 40-50 years. After age 60 years, the prevalence of hypothyroidism may be as high as 8-10% in women.
Potential physical examination findings include the following:
Pseudomyotonic reflexes - Prolonged relaxation phase, usually at least twice as long as the contraction phase
Hypothermia (especially in myxedema coma)
Skin changes - Dry, cool, coarse, and thickened with a yellowish appearance
Subcutaneous tissues - Nonpitting, waxy, dry edema secondary to accumulation of polysaccharides
Loss of axillary and pubic hair
Pallor
Loss of outer one third of eyebrows
Abdominal distention
Goiter
Unsteady gait/ataxia
Pericardial effusion
Dull facial expression
Coarsening or huskiness of voice
Periorbital edema
Bradycardia, narrow pulse pressure
Macroglossia
Thyroidectomy scar - In patients with altered mental status, suggests myxedema coma as a potential cause
A Swedish study, by Mourtzinis et al, found the rates of hypothyroidism and hyperthyroidism in patients with atrial fibrillation to be 5.9% and 2.3%, respectively, compared with 3.7% and 0.8%, respectively, in controls.[8]
The most common etiology of hypothyroidism worldwide is iodine deficiency as associated with endemic goiter. Conversely, a study among Chinese patients also demonstrated a significant increase in overt hypothyroidism in those with an excessive intake of iodine.[9] Within the United States and developed nations, the major causes of hypothyroidism are autoimmune destruction of the thyroid gland (eg, Hashimoto thyroiditis) and iatrogenic secondary to the treatment of Graves disease (surgical or radioactive iodine ablation of the thyroid gland). Primary hypothyroidism (dysfunction of the thyroid gland) accounts for up to 90-95% of cases. Secondary hypothyroidism (dysfunction of the pituitary or hypothalamus) accounts for most of the remainder of cases. ED management rarely requires distinguishing between primary and secondary origins.
Primary causes include autoimmune, idiopathic, postoperative, and congenital etiologies; radiation; radioiodine therapy; iodine deficiency; metabolic disorders; and medications (eg, lithium, amiodarone, phenytoin, carbamazepine, iodides). Furthermore, those with underlying autoimmune thyroiditis are susceptible to disease progression while taking these medications. Antineoplastic agents are also recognized to cause thyroid dysfunction in 20-50% of patients. Since symptoms of hypothyroidism may be vague and attributed to adverse effects of medication, it may be appropriate to monitor thyroid function regularly during treatment.[10]
A retrospective study by Spiegel et al indicated that small-for-gestational-age infants are at increased risk for childhood hypothyroidism, with an adjusted odds ratio of 3.2.[11]
Secondary causes include pituitary and hypothalamic disorders such as trauma, neoplasm, irradiation, and infiltrative diseases including sarcoidosis or amyloidosis.
In a patient with underlying hypothyroidism, inciting factors responsible for developing myxedema coma are numerous and include infection, trauma, cold exposure, or medications such as sedatives and anesthetics.
The following measurements and studies are indicated in hypothyroidism[4] :
Electrolytes
Hyponatremia is common secondary to extracellular volume expansion produced by elevated antidiuretic hormone.
Blood glucose level ranges from normal to low secondary to decreased gluconeogenesis and reduced insulin clearance.
Creatine phosphokinase (CPK), aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT), and lactate dehydrogenase (LDH) levels may be elevated in myxedema coma due to increased muscle membrane permeability. Creatine kinase (CK)-myocardial band (MB) levels are typically normal.
Arterial blood gas (ABG): Hypoventilation commonly results in hypercapnia and hypoxia in patients with myxedema coma.
Urinalysis: Evaluate for source of infection.
Secondary studies
Thyroid function studies may not be immediately available to assist in clinical decision making in the ED.
Thyroid-stimulating hormone (TSH) is elevated in primary hypothyroidism, but it may be normal or low in secondary causes of hypothyroidism.
Free thyroxine (T4) levels are low.
Triiodothyronine (T3) resin uptake is decreased.
Free T4 index (T3 resin uptake x total serum T4) is low.
Critically ill patients may develop euthyroid sick syndrome, which must not be confused with a primary thyroid abnormality. These patients have low to normal TSH and T4 levels with low T3 levels.
An enlarged cardiac silhouette in a chest radiograph may suggest pericardial effusion. A chest radiograph depicting a pericardial effusion is shown in the image below.
View Image
Pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette.
However, chest radiography is reported to have a 30% false-negative rate in detecting hypothyroid pericardial effusions.
Chest radiography can help detect pulmonary infections often associated with myxedema coma.
Acute abdominal series: An ileus may be associated with hypothyroidism, and it may be present in myxedema coma.
Head CT scan (noncontrast)
In patients with altered mental status, the scan may be helpful in ruling out other etiologies such as intracerebral hemorrhage.
The scan may be helpful in ruling out other etiologies of altered mental status, such as intracerebral hemorrhage.
Echocardiography: Perform this study if pericardial effusion is suspected.
Patients with myxedema coma may present in extremis; implement initial resuscitative measures, including intravenous (IV) access, cardiac monitoring, and oxygen therapy, as indicated. Mechanical ventilation is indicated for patients with diminished respiratory drive or obtundation.
Evaluate for life-threatening causes of altered mental status (eg, bedside glucose, pulse oximetry).
If myxedema coma is suspected on clinical impression, start IV thyroid hormone treatment.
Confirmatory tests often are not available to an ED physician.
With a diagnosis of myxedema coma, initiate hormonal therapy.
Myxedema coma may lead to profound hemodynamic instability and airway compromise. Emergency physicians should anticipate a potentially difficult airway in patients with myxedema coma.[5]
Investigate immediately for inciting events such as infection.
Treat respiratory failure with appropriate ventilatory support. The condition often requires mechanical ventilation. Treat underlying pulmonary infection.
Hypotension may respond to crystalloid infusion. Occasionally, vasopressive agents are required. In refractory cases, hypotension may resolve with thyroid hormone replacement.
Treat hypothermia. Most patients with myxedema coma respond to passive rewarming measures such as blankets and removal of cold or wet clothing; aggressive rewarming may lead to peripheral vasodilatation and hypotension. However, hemodynamically unstable patients with profound hypothermia require active rewarming measures. Treat hyponatremia initially with water restriction; however, if sodium levels are less than 120 mEq/L or any seizures occur, hypertonic saline is indicated.
Avoid medications such as sedatives, narcotics, and anesthetics. Metabolism of these agents may be slowed significantly, causing prolonged effects.
Initiate thyroid hormone replacement as the mainstay therapy for patients with myxedema coma. Patients may remain refractory to other treatment and supportive therapies until thyroid hormone replacement takes effect. Infusing thyroid hormone in the euthyroid patient is unlikely to result in significant morbidity except in patients with ischemic heart disease. Hormonal therapy should be instituted early in patients with a high clinical suspicion of myxedema coma prior to laboratory confirmation.
Monitor the patient's heart during hormone treatment, decreasing or discontinuing the dosage with any evidence of ischemia or dysrhythmia.
The magnitude of hypothyroidism dictates dose and route. Mild cases may be treated with gradual oral replacement, but patients with myxedema coma usually require large doses of IV replacement. General guidelines suggest administration of intravenous levothyroxine at a dose of 500-800 mcg. Alternatively, intravenous liothyronine can be given at a dose of 25 mcg.
Administer antibiotics if infection is suspected to be a precipitating event.
Physicians often recommend glucocorticoid replacement therapy because adrenal insufficiency may be concomitant (especially in patients with secondary hypothyroidism).
Clinical Context:
Liothyronine is a synthetic form of natural thyroid hormone (T3) converted from thyroxine (T4); its short duration of activity allows quick dose adjustments in the event of overdosage.
The prognosis of hypothyroidism is good with early treatment. However, once the disease has progressed to myxedema coma, the mortality rate may exceed 20% in the treated population. Relapses occur if treatment is discontinued.
The mortality rate in myxedema coma has historically been as high as 80%. Some data suggest that aggressive management and early recognition have improved the mortality rate to 15-20%. However, a more recent observational study was unable to show significant differences in outcome based on replacement therapeutic methods, with a mortality rate remaining high at 40%.[13]
The aforementioned study by Ono et al reported that, as revealed through multivariable logistic regression, a higher inhospital mortality rate in myxedema coma was associated with older age and catecholamine use (with or without steroids).[7]
A study by Sato et al suggested that in patients with heart failure, those with subclinical hypothyroidism have a worse prognosis, finding a significant increase in the rates of cardiac events and all-cause mortality in heart failure patients in the study with subclinical hypothyroidism compared with those who were euthyroid.[14]
A literature review by Chrysant suggested that levothyroxine supplementation for subclinical hypothyroidism in younger persons (specifically, those with a thyroid-stimulating hormone [TSH] level of >4.0 mIU/L) is more effective with regard to cardiovascular disease, heart failure, and mortality than it is in older patients. Chrysant also suggested that such treatment in older patients be individualized according to symptom presence and TSH level and that it commence when TSH levels are 10 mIU/L or above. He also advised that, in order to avoid harmful cardiovascular effects in older persons related to overtreatment, it be administered at low doses in these patients.[15]
What are hypothyroidism and myxedema coma?What is the pathophysiology of hypothyroidism?What is the prevalence of hypothyroidism and myxedema coma in the US?What is the global prevalence of hypothyroidism and myxedema coma?What are the racial predilections of hypothyroidism and myxedema coma?What are the sexual predilections of hypothyroidism and myxedema coma?Which age groups have the highest prevalence of hypothyroidism and myxedema coma?What are the signs and symptoms of hypothyroidism?Which physical findings are characteristic of hypothyroidism and myxedema coma?What causes hypothyroidism?What causes myxedema coma?What are the differential diagnoses for Hypothyroidism and Myxedema Coma?What is the role of lab tests in the workup of hypothyroidism and myxedema coma?What is the role of imaging studies in the workup of hypothyroidism and myxedema coma?Which core temperatures are characteristic of myxedema coma?What is the role of EKG in the workup of hypothyroidism and myxedema coma?What is included in prehospital care of hypothyroidism and myxedema coma?How is myxedema coma treated?Which specialist consultations are beneficial to patients with hypothyroidism and myxedema coma?What is the role of medications in the treatment of hypothyroidism and myxedema coma?Which medications in the drug class Corticosteroids are used in the treatment of Hypothyroidism and Myxedema Coma?Which medications in the drug class Thyroid products are used in the treatment of Hypothyroidism and Myxedema Coma?What is included in the inpatient care of hypothyroidism and myxedema coma?What are the possible complications of hypothyroidism?What is the prognosis of hypothyroidism and myxedema coma?What is included in patient education about hypothyroidism and myxedema coma?
Erik D Schraga, MD, Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Romesh Khardori, MD, PhD, FACP, Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School
Disclosure: Nothing to disclose.
Acknowledgements
Jerome FX Naradzay, MD, FACEP Medical Director, Consulting Staff, Department of Emergency Medicine, Maria Parham Hospital; Medical Examiner, Vance County, North Carolina
Jerome FX Naradzay, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
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