Myxedema coma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Myxedema coma constitutes the highest expression of untreated hypothyroidism and results from depletion severe and prolonged thyroid hormones. The term coma is considered to be misleading because the majority of patients with this syndrome are not initially in a comatose condition. Myxedematous coma is believed to triggered by a variety factors that cause a systemic compromise with fatal outcome if not mediating an early diagnosis and intensive treatment. The typical picture of myxedematous coma is lethargy that progresses to stupor and finally coma. In addition to coma, the clinical characteristics of hypothyroidism such as dry skin, alopecia, hoarse voice, periorbital edema and generalized macroglossia and hyporeflexia are also present.

In 874, Gull was the first physician to describe hypothyroidism under the name myxedema due to its characteristics of swollen skin and its mucin content. In 1883, Semon was the first to establish a relationship between patients undergoing thyroidectomy and later developing symptoms of myxedema. In 1888, Clinical Society of London presented a paper describing that extreme loss of thyroid hormone can lead to cretinism and myxedema.

There is no established classification system for myxedema coma.

Myxedema coma occurs as a result of long-standing, undiagnosed, or untreated hypothyroidism. Myxedema coma is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cell metabolism. Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems. Reduced metabolism and decreased oxygen results in hypothermia and decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents and can precipitate myxedema coma.

Common causes of myxedema coma include sepsis, exposure to cold weather, central nervous system depressants (sedatives, narcotics, antidepressants), trauma, surgery, stroke, congestive heart failure, burns, intravascular volume contraction (GI blood loss, diuretic use), myocardial infarction, and metabolic derangements.

Myxedema must be differentiated from other causes of lower limb edema-like chronic venous insufficiency, acute deep venous thrombosis, lipedema, lymphatic filariasis, cellulitis and causes of generalized edema.

Myxedema coma is the extreme expression of severe hypothyroidism and fortunately is rare, with an incidence rate of 0.022 per 100,000 per year. Myxedema coma is more commonly seen in older age group.

Common risk factors in the development of myxedema coma include hypothermia, cerebrovascular accidents, congestive heart failure, infections, drugs, gastrointestinal bleeding, trauma, and electrolyte disturbances.

There is insufficient evidence to recommend routine screening for myxedema coma.

If left untreated, myxedema coma can be fatal leading to death. Common complications of myxedema coma include treatment-induced congestive heart failure in patients with coronary artery disease, increased susceptibility to infection and organic psychosis with paranoia. The mortality rate in myxedema coma is 20% to 25% despite aggressive therapy.

The diagnosis of myxedema coma is made when the three key diagnostic features of myxedema coma are present, which include altered mental status, hypothermia or absence of fever and a precipitating event such as cold exposure, infection, drugs.

The function of all organ systems and various metabolic pathways are compromised in hypothyroidism. The cardinal symptoms of myxedema coma are the sensory impairment and hypothermia. The accumulation in the interstitial tissue of mucopolysaccharides and water leads to myxedema that compromises a large part of the tissues. Myxedema coma patients may be disoriented, therefore, the patient interview may be difficult. In such cases, history from the care givers or the family members may need to be obtained.

The physical examination findings of myxedema coma will reveal the characteristic signs of hypothyroidism, and not being able to obtain patient’s history, it is often very useful to search for of other signs that guide the diagnosis of myxedema coma such as a cervical scar (history of thyroid surgery), vitiligo, hyperpigmentation, ophthalmopathy.

Myxedematous coma should be considered in any patient who is comatose or who has some degree of deterioration of the sensorium with hypothermia or absence of fever in the presence of infection, hyponatremia and/or hypercapnia. Performing a thyroid routine test is considered the best initial step in the management of patients with myxedema coma.

Electrocardiographic findings of myxedema coma include bradycardia, varying degrees of heart block, low voltage, nonspecific ST-segment changes, flattened or inverted T waves, prolonged Q-T interval, and ventricular or atrial arrhythmias.

There are no x-ray findings associated with myxedema coma. However, an x-ray may be helpful in the diagnosis of complications of myxedema coma, which include cardiomegaly, pericardial effusion, congestive heart failure, or pleural effusion.

There are no echocardiography/ultrasound findings associated with myxedema coma.

There are no CT scan findings associated with myxedema coma but a CT scan of the brain is done to rule out CNS etiology.

There are no MRI findings associated with myxedema coma.

There are no other imaging findings associated with myxedema coma.

There are no other diagnostic studies associated with myxedema coma.

All the patients with myxedema coma should be shifted to ICU and treatment should be started as quickly as possible. Given the clinical suspicion of myxedema coma, initiate replacement therapy without waiting for laboratory results. The empirical use of glucocorticoids should be part of the initial therapeutic protocol, in view of the observations which indicate that severe hypothyroidism induces a lower adrenal response to stress. This is independent of whether or not there is simultaneous adrenal insufficiency. Since thyroid hormone speeds up the metabolism of cortisol and its plasma levels may be decreased in the presence of adrenal insufficiency, the glucocorticoids should always be given prior to thyroid replacement because otherwise, they could precipitate an adrenal crisis. Hydrocortisone will be given in doses of stress, 50- 100 mg intravenously (IV) every 6-8 h for 7 to 10 days or until hemodynamically stabilizes the patient. Suspend if laboratory commitment is discarded of the adrenal axis. Identify and properly treat the precipitating factor.

Surgical intervention is not recommended for the management of myxedema coma.

Effective measures for the primary prevention of myxedema coma include regular follow-up care, undergoing regular blood testing in order to adapt hormone replacement therapy and compliant with medications once the diagnosis of hypothyroidism is made.

There are no secondary preventive measures available for myxedema coma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

In 874, Gull was the first physician to describe hypothyroidism under the name myxedema due to its characteristics of swollen skin and its mucin content. In 1883, Semon was the first to establish a relationship between patients undergoing thyroidectomy and later developing symptoms of myxedema. In 1888, Clinical Society of London presented a paper describing that extreme loss of thyroid hormone can lead to cretinism and myxedema.

• In 874, Gull was the first physician to describe hypothyroidism under the name myxedema due to its characteristics of swollen skin and its mucin content.^[1][2]
• Mydematous coma was initially described by William Ord of the St. Thomas Hospital of London in 1879.
• In 1883, Semon was the first to establish a relationship between patients undergoing thyroidectomy and later developing symptoms of myxedema.
• In 1888, Clinical Society of London presented a paper describing that extreme loss of thyroid hormone can lead to cretinism and myxedema.
• In 1891, Murray was the first physician to discover a cure for myxedema by using hypodermic injections of sheep thyroid extract.
• In 1983, Vincent Summe, English physician of the Walton Hospital of Liverpool, was the first to coin the term myxedema coma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

There is no established classification system for myxedema coma.

There is no established classification system for myxedema coma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Myxedema coma occurs as a result of long-standing, un-diagnosed, or untreated hypothyroidism and is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cellular metabolism. Long-standing hypothyroidism results in reduced metabolic rate and decreased oxygen consumption, which affects all organ systems. Reduced metabolism and decreased oxygen results in hypothermia and decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents and can precipitate myxedema coma.

• Myxedema coma occurs as a result of long-standing, undiagnosed, or untreated hypothyroidism.^[1][2][3][4]
• Myxedema coma is usually precipitated by a systemic illness.

• Thyroid hormone plays an important role in cellular metabolism.
• Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all organ systems.
• Reduced metabolism results in hypothermia.
• Reduced metabolism and decreased oxygen also result in decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents; this can precipitate myxedema coma.
• Even in severe hypothyroidism, a balance of metabolic homeostasis is achieved through adaptive neurovascular mechanisms. However, in conditions such as respiratory or urinary tract infections, cardiac, acute myocardial infarction or stroke interfere with this adaptive mechanisms by decreasing the blood volume and ventilation triggering myxedema coma.

• Myxedema coma can result from any of the causes of hypothyroidism, most commonly chronic autoimmune thyroiditis.
• Myxedema coma can also occur in patients who had thyroidectomy or underwent radioactive iodine therapy for hyperthyroidism.
• Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone.

Hypothyroidism

Precipitating Factor

↓T4

↓ IntracellularT3

Hypothalamus

Respiratory

Cardiovascluar

Renal

↓ Thermogenesis

Hypercapnia Hypoxia

↓ Inotropic Bradycardia

↓ Volume status

Hypothermia

Hypoventilation

↓ Cardiac output ↓ Blood volume

↓ GFR ↑ ADH

Alteration of mental state

Cerebral anoxia

↓Arterial pressure/shock

Hyponatremia Edema

Myxedema Coma

Organ System	Effect due to Decreased Thyroid Hormone	Manifestation
Cardiovascular	Cardiac contractility impaired: Leading to reduced stroke volume Low cardiac output Bradycardia Hypotension Reduced stroke volume Accumulation of fluid rich in mucopolysaccharides within the pericardial sac	Hypotension Narrowed pulse pressure Edema Pericardial effusions
Neurologic	Altered brain function due to: Reduced oxygen delivery and consumption Decreased glucose utilization Reduced cerebral blood flow	Altered consciousness
Pulmonary	Central depression of ventilatory drive: Hypoxia Hypercapnia	Hypoventilation
Renal	Reduced glomerular filtration rate because of: Low cardiac output Peripheral vasoconstriction Rhabdomyolysis Low volume stimulates Antidiuretic hormone impairs water excretion leading to hyponatremia	Dysuria Urinary frequency Nocturia
Gastrointestinal	Mucopolysaccharide infiltration and edema results in: Malabsorption Gastric atony Impaired peristalsis Paralytic ileus Megacolon	GI bleeding Ascites Constipation
Hematologic	Coagulopathy Due to decrease in production of factors V, VII, VIII, IX, and X Hemorrhage and vitamin B12 deficiency	Bleeding Anemia

Common conditions associated with myxedema coma include:

• Type 1 diabetes
• Addison’s disease
• Pernicious anemia
• Vitiligo
• Rheumatoid arthritis
• Premature ovarian failure

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Common causes of myxedema coma include sepsis, exposure to cold weather, central nervous system depressants (sedatives, narcotics, antidepressants), trauma, surgery, stroke, congestive heart failure, burns, intravascular volume contraction (GI bleeding, diuretic use), myocardial infarction, and metabolic disorders.

Myxedema coma may be caused when the thyroid is severely compensated and is not able to produce enough thyroid hormone. It is a rare condition that is not happening frequently.

Common causes of myxedema coma include:^[1]

• Sepsis
• Exposure to cold weather
• Central nervous system depressants (sedatives, narcotics, antidepressants)
• Trauma, surgery
• Stroke, congestive heart failure, burns
• Intravascular volume contraction (GI bleeding, diuretic use)
• Myocardial infarction
• Metabolic disorders

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Myxedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lipedema, lymphatic filariasis, cellulitis and causes of generalized edema.

Myxedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lipedema, lymphatic filariasis, cellulitis and causes of generalized edema.

Diseases	History	Symptoms						Signs	Gold standard Investigation to diagnose
		Onset	Pain	Fever	Laterality	Scrotal swelling	Symptoms of primary disease
Myxedema	History of untreated hypothyroidism Infiltration of the skin with glycosaminoglycans with associated water retention	Chronic	+	–	Bilateral	–	+ (hypothyroidism )	Pretibial myxedema	Thyroid function tests
Lymphatic filariasis	History of living in endemic area or travelling to it	Chronic	+	+	Bilateral	+	–	Hepatomegaly Lymphedema Elephantiasis Lymphangitis Hydrocele Scrotal elephantiasis Lymphadenopathies Rhonchi may be present in patients with Pulmonary tropical eosinophilia syndrome	Preparing blood smears Thick smears Thick smears consist of a thick layer of dehemoglobinized (lysed) red blood cells (RBCs) Thick smears allow a more efficient detection of parasites (increased sensitivity) Thin smears consist of blood spread in a layer such that the thickness decrease By the ultrasound, the following findings can be observed: Dilated lymphatic channels Living worms tend to be in motion which called “filarial dance” sign.
Chronic venous insufficiency	History of untreated varicose veins Painful bilateral lower limb swelling that increases with standing and decreases by rest and leg elevation	Chronic	+	–	Bilateral	+ (If congenial)	–	Typical varicose veins Skin change distribution correlate with varicose veins sites in the medial side of ankle and leg Reduction of swelling with limb elevation	Duplex ultrasound will demonstrate typical findings of venous valvular insufficiency
Acute deep venous thrombosis	History of prolonged recumbency Classic symptoms of DVT include acute unilateral swelling, pain, and erythema	Acute	+	–	Unilateral	–	May be associated with primary disease mandates recumbency for long duration	Dilated superficial veins Difference in calf diameter is twice as likely to have DVT(most impotant sign )[1] Calf pain on passive dorsiflexion of the foot (Homan’s sign) isn’t realiable sign	Compression ultrasonography (CUS) with doppler is the diagnostic test of choice D-dimer level is used for unprobable cases
Lipedema	Family history especially in women; X-linked dominant or autosomal dominant condition[2] Abnormal deposition of fat and edema and easy bruising	Chronic	+	–	Bilateral	–	–	Tender with palpation Negative Semmer sign to differentiate from lymphedema[3] Pinching the skin on the upper surface of the toes If it is possible to grasp a thin fold of tissue then it is negative result In a positive result, it is only possible to grasp a lump of tissue.	MRI offers strong qualitative and quantitative parameters in the diagnosis of lipedema [4]
(Cellulitis–erysipelas-skin abscess)	Acute painful swelling Fever	Acute	+	+	Unilateral	–	–	Tenderness, hotness, and may be fluctuation if abscess formed Lymphangitis in nearby lymph nodes Toxemia and fever in severe cases Cellulitis involves the deeper dermis and erysipelas involves the upper dermis[5]	Usually it doesn’t need any laboratory tests to diagnose[6] Blood cultures are warranted for patients in the following circumstances:[7] Systemic toxicity Extensive skin or soft tissue involvement Underlying comorbidities Persistent cellulitis In patients with recurrent cellulitis, serologic testing for beta-hemolytic streptococci is a good diagnostic tool[8]
Other causes of generalized edema	History of chronic general condition (cardiac–liver–renal)	Chronic	–	–	Bilateral	–	+		According to the primary cause ( Echo- LFTs– RFT)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Myxedema coma is the extreme expression of severe hypothyroidism and fortunately is rare, with an incidence rate of 0.022 per 100,000 per year. Myxedema coma is more commonly seen in older age group.

The incidence of myxedema coma is approximately 0.022 per 100,000 per year.^[1]

Myxedema coma is more commonly seen in older age group.

Myxedema coma is more common in females.

Myxedema coma is more common in Whites and Asians than in African-Americans.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Common risk factors in the development of myxedema coma include hypothermia, cerebrovascular accidents, congestive heart failure, infections, drugs, gastrointestinal bleeding, trauma, and electrolyte disturbances.

Common risk factors in the development of myxedema coma include:^[1][2][3]

• Hypothermia
• Cerebrovascular accidents
  • Stroke
  • TIA
• Congestive heart failure
• Infections
• Drugs
  • Anesthetics
  • Narcotics
  • Amiodarone
  • Lithium carbonate
• Gastrointestinal bleeding
• Trauma
• Metabolic disorders
  • Hypoglycemia
  • Hyponatremia
  • Acidosis
  • Hypercalcemia
  • Hypoxemia
  • Hypercapnia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

There is insufficient evidence to recommend routine screening for myxedema coma.

There is insufficient evidence to recommend routine screening for myxedema coma.