Myxedema coma is preceded by a long history of hypothyroidism-related symptoms, such as generalized fatigue, cold intolerance, constipation, and dry skin, which slowly progress into more pronounced clinical manifestations such as lethargy, delirium, and coma. This progression is usually accelerated by the triggers mentioned above, like heart failure, trauma, or infection. Since these symptoms are non-specific, hypothyroidism can frequently go undiagnosed and clinically missed.

Comatose state does not necessarily occur in every myxedema coma episode, but certainly it characterizes the worst cases. The usual signs instead, which can be typically observed in all cases, include weight gain, the already mentioned fatigue, constipation, and cold intolerance. These are usually coupled with coarsened hair, deepened voice and dry, pale, and cool skin. They are commonly followed by an hypothermic state characterized by core body temperatures less than 35.5 C°. Furthermore, the hypotensive state is usually associated with bradycardia and hypoventilation, that in turn might cause sleep apnea. 

In any case, the signs involve almost all the organic systems. As previously said, the skin appears cool, pale, and dry, usually associated with brittle nails ecchymoses, purpura, and sallowness due to carotenemia. It is also possible to observe signs of periorbital and non-pitting edema on hands and feet, as well as enlarged tonsils, facial swelling, and thinning of hair [5]. Slowed respiration rate, congestion, and hypoventilation may be present. The thyroid may appear enlarged or with scars indicating the presence of previous thyroidectomy. Soft sounds, coupled with diminished apical impulse, bradycardia and pericardial effusion, can be detected in the heart, and in the abdomen and bladder there are clear signs of distension with the bowel sounds appearing diminished or absent.

The neuromuscular system is also largely affected, presenting the classical signs of confusion, stupor, slow speech, obtundation, and reflexes with a slow relaxation phase, usually followed by more pronounced signs such as seizures and coma. Apathy, low mood, and a general cognitive decline can also frequently observed and are often mixed up with the symptoms of dementia and depression.

It is important to notice that many patients might have been treated with diuretics for edematous states before showing the signs of myxedema coma. This condition might mask the development and delay the final diagnosis [11], causing a marked increase in the mortality of this disorder [12].

• Hypothermia

  A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. [ncbi.nlm.nih.gov]

  The child with hypothermia and shock most likely has a super bad infection… but that infection may just be triggering myxedema coma. Altered Mental Status and Hypoxia doesn’t mean pneumonia necessarily. [pedemmorsels.com]

• Fatigue

  Patients with hypothyroidism typically have a history of fatigue, weight gain, constipation and cold intolerance. Physicians should include hypothyroidism in the differential diagnosis of every patient with hyponatremia. [ncbi.nlm.nih.gov]

  The usual signs instead, which can be typically observed in all cases, include weight gain, the already mentioned fatigue, constipation, and cold intolerance. [symptoma.com]

  The clinical manifestations of hypothyroidism reflect one of two changes: 1) Slowed metabolism – accounts for the fatigue, cold intolerance, slow movement and speech, constipation, bradycardia, weight gain, delayed relaxation of DTRs 2) Accumulation of [errolozdalga.com]

  Images in Clinical Medicine Joyce Kim, M.D. 2 Citing Articles A 56-year-old woman, who had not received medical care for 30 years, presented to the emergency department with progressively worsening fatigue and confusion. [nejm.org]

• Swelling

  The classic skin changes are: swelling of your face, which can include your lips, eyelids, and tongue swelling and thickening of skin anywhere on your body, especially in your lower legs Severely advanced hypothyroidism can lead to what is called a myxedema [healthline.com]

  […] now the swelling is gone. [medhelp.org]

  When to Seek Medical Care People who have hypothyroidism and develop fever, changes in behavior or mental status, slowness of breath, or increased swelling of the hands and feet should be taken to an emergency department. [webmd.com]

• Sepsis

  Two-thirds of the patients presented in the fall and winter; the most common precipitating events was sepsis (42.5%). More than three-quarters of the patients were admitted to the ICU. Median free thyroxine values were 0.39 ng/L. [healio.com]

  Myxedema Coma is difficult to distinguish from sepsis, and since infection is often the precipitating event in a patient with preexisting hypothyroidism, generally the patients must receive empiric antibiotics until sepsis is ruled out. [errolozdalga.com]

  MC, autoimmune hypothyroidism, pneumonia and sepsis were diagnosed. Gastric levothyroxine, intravenous dexamethasone and antibiotics were administered. [ncbi.nlm.nih.gov]

• Cold Intolerance

  Patients with hypothyroidism typically have a history of fatigue, weight gain, constipation and cold intolerance. Physicians should include hypothyroidism in the differential diagnosis of every patient with hyponatremia. [ncbi.nlm.nih.gov]

  The usual signs instead, which can be typically observed in all cases, include weight gain, the already mentioned fatigue, constipation, and cold intolerance. [symptoma.com]

  The clinical manifestations of hypothyroidism reflect one of two changes: 1) Slowed metabolism – accounts for the fatigue, cold intolerance, slow movement and speech, constipation, bradycardia, weight gain, delayed relaxation of DTRs 2) Accumulation of [errolozdalga.com]

  Patients initially have cold intolerance that progresses to severe loss of heat from the body. [ehealthwall.com]

• Pneumonia

  A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. [ncbi.nlm.nih.gov]

  Altered Mental Status and Hypoxia doesn’t mean pneumonia necessarily. Add thyroid dysfunction to your list of items to consider in the patient with altered mental status. [pedemmorsels.com]

  She's then transferred to the medical unit with orders for daily levothyroxine and treatment for pneumonia. Before discharge, teach Ms. [journals.lww.com]

• Hypercapnic Respiratory Failure

  Cell 140:88–98 Article PubMed CAS Google Scholar Abbasi B, Sharif Z, Sprabery LR (2010) Hypokalemic thyrotoxic periodic paralysis with thyrotoxic psychosis and hypercapnic respiratory failure. [link.springer.com]

• Constipation

  Patients with hypothyroidism typically have a history of fatigue, weight gain, constipation and cold intolerance. Physicians should include hypothyroidism in the differential diagnosis of every patient with hyponatremia. [ncbi.nlm.nih.gov]

  Hypothermia Bradycardia Large Fontanelle Prolonged Jaundice CHILDREN and ADOLESCENTS Goiter Fatigue Constipation Bradycardia Poor Growth Cold intolerance Delayed Pubertal Development Menstrual irregularities Myxedema Coma is Rare in children, but lethal [pedemmorsels.com]

  The usual signs instead, which can be typically observed in all cases, include weight gain, the already mentioned fatigue, constipation, and cold intolerance. [symptoma.com]

  The clinical manifestations of hypothyroidism reflect one of two changes: 1) Slowed metabolism – accounts for the fatigue, cold intolerance, slow movement and speech, constipation, bradycardia, weight gain, delayed relaxation of DTRs 2) Accumulation of [errolozdalga.com]

  Presenting symptoms: -90% of cases are elderly females in the winter – Sx of hypothyroidism ( weight gain, cold intolerance, constipation, hair loss …) – Hypothermia (often profound-even down to 27 Celsius) – AMS (coma not common- more likely to see lethargy [dailyem.wordpress.com]

• Failure to Thrive

  Hypothermia Hypoglycemia Changes in Mental Status (although, not necessarily coma) Severe Hypothyroidism Failure to thrive or poor growth history Infection Most common trigger Particularly pneumonia and sepsis Trauma Cold Exposure Anesthesia Treat the [pedemmorsels.com]

  Methods/Results: A 10-month-old female presented with ptosis, lethargy, dysphagia, and failure to thrive (FTT). She developed hypotension, bradycardia, hypothermia, and apnea requiring intubation. [karger.com]

• Heart Failure

  Session Title: FIT Clinical Decision Making: Heart Failure and Cardiomyopathies Abstract Category: Heart Failure and Cardiomyopathies Presentation Number: 1109-151 [jacc.org]

  Due to the unexplained severe heart failure and concern for cardiogenic shock, we proceeded with right and left heart catheterization. [onlinejacc.org]

  These triggering factors include infections, especially those affecting lungs and kidneys, heart failure, stroke, trauma, some types of surgery, and drug therapies. [symptoma.com]

  These life-threatening symptoms may occur: Mental deterioration such as apathy, confusion, and psychosis Extremely low body temperature (hypothermia) Extremely slow heartbeat (fewer than 60 beats a minute) Heart failure Respiratory failure Death can occur [myhealth.alberta.ca]

  Patient Management Administer intravenous fluids as ordered to maintain BP >90 mm Hg; carefully monitor for fluid overload and development of heart failure. [nursingcrib.com]

• Slow Pulse

  […] heart rate, slow pulse and confusion. [symptoma.com]

• Large Fontanel

  Fontanelle Prolonged Jaundice CHILDREN and ADOLESCENTS Goiter Fatigue Constipation Bradycardia Poor Growth Cold intolerance Delayed Pubertal Development Menstrual irregularities Myxedema Coma is Rare in children, but lethal. [pedemmorsels.com]

• Facial Swelling

  It is also possible to observe signs of periorbital and non-pitting edema on hands and feet, as well as enlarged tonsils, facial swelling, and thinning of hair. Slowed respiration rate, congestion, and hypoventilation may be present. [symptoma.com]

• Stroke

  These triggering factors include infections, especially those affecting lungs and kidneys, heart failure, stroke, trauma, some types of surgery, and drug therapies. [symptoma.com]

  Precipitating factors may include (but are limited to) infection, trauma, surgery, heart failure, stroke, or central nervous system depressants. Hypothyroidism depresses metabolic rate, thus seriously affecting all body system. [nursingcrib.com]

  Cardiovascular Cardiac contractility is impaired, leading to reduced stroke volume, low cardiac output, bradycardia and sometimes hypotension. [6] Reduced stroke volume in severe cases may also be due to pericardial effusions caused by the accumulation [emedicine.medscape.com]

  Some of these include MI, infection/sepsis, stroke, PE, exposure to drugs that suppress the CNS, and prolonged exposure to cold. [sinaiem.org]

• Altered Mental Status

  LT4 load is safe and effective at reversing symptoms, particularly [altered mental status], within a short period of time ( For more information: Wu KC. Oral #221. [healio.com]

  Myxedema coma (MC), a medical emergency defined as severe hypothyroidism leading to altered mental status, is more common in older women with hypothyroidism. [ncbi.nlm.nih.gov]

• Stupor

  Symptoms include hypoglycemia, hyponatremia, hypothermia, hypoventilation, progressive weakness, stupor, shock, and death. [boardprep.net]

  The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. [ncbi.nlm.nih.gov]

  […] and coma with mcc 081 Nontraumatic stupor and coma without mcc 793 Full term neonate with major problems Convert E03.5 to ICD-9-CM Code History 2016 (effective 10/1/2015) : New code (first year of non-draft ICD-10-CM) 2017 (effective 10/1/2016) : No [icd10data.com]

• Forgetful

  Don’t forget to take the quiz on myxedema coma. [registerednursern.com]

  Think common, but don’t forget complicated! The child with hypothermia and shock most likely has a super bad infection… but that infection may just be triggering myxedema coma. Altered Mental Status and Hypoxia doesn’t mean pneumonia necessarily. [pedemmorsels.com]

  […] tiredness weight gain drooping eye shock decreased breathing confusion apathy or depression psychosis constipation coarse hair goiter low energy reduced mobility low body temperature People should also note that a myxedema coma can occur in patients who forget [medicalnewstoday.com]

• Cerebellar Ataxia

  ProlactinNeuromuscular• Aches and pains• Muscle stiffness• Carpel tunnel syndrome• Deafness, Hoarseness• Cerebellar ataxia• Delayed DTR, Myotonia• Depression, PsychosisGastro-intestinal• Constipation, Ileus, AscitesDermatological• Dry flaky skin and hair [slideshare.net]

  Cerebellar ataxia, intention tremor, nystagmus, and difficulty with coordinated movements may occur. Twenty-five percent of those who develop myxedema coma initially present with grand mal seizure. [emjournal.net]

  Cerebellar ataxia may occur, especially in elderly people, and is associated with an unsteady gait and intention tremor. [clinicalgate.com]

The diagnosis of myxedema coma is largely based on laboratory studies. In particular, levels of T3 and T4 should be low or even undetectable, while the level of TSH should usually be elevated due to a primary thyroid disorder. Complete blood count should detect the presence of infection, while Pan-culture is used to rule out sepsis. Equally important are also tests to measure the levels of electrolytes, creatinine and glucose, to reveal low serum osmolarity, decreased renal perfusion, and adrenal insufficiency.

Imagining studies could be useful in the diagnosis, especially chest radiography which is strongly recommended to detect cardiomegaly, congestive heart failure, and pericardial and pleural effusion. Electrocardiography might also be useful, especially to detect signs of sinus bradycardia.

• Hypercapnia

  […] muscle weakness Mechanical obstruction by a large tongue Sleep apnea Degree of hypoventilation and hypercapnia is not usually clinically important Hyponatremia Found in approx ½ of pts with myxedema coma May contribute to the decrease in mental status [lilywhite.us]

  […] hoarse voice periorbital oedema CVS: non-pitting oedema of hands and feet, bradycardia, hypotension refractory to vasopressors, reduced contractility, pericardial effusion RESP: respiratory depression, impaired respiratory muscle function, hypoxia and hypercapnia [lifeinthefastlane.com]

  Low blood sugar, low blood pressure, hyponatremia, hypercapnia, hypoxia, slowed heart rate, and hypoventilation may also occur.[4] Myxedema, although included in the name, is not necessarily seen in myxedema coma. [en.wikipedia.org]

  […] worsening and she was transferred to a Universitary Hospital, where myxedema coma was suspected (history of untreated autoimmune hypothyroidism, apparently normal temperature – 36 °C despite the infection, bradycardia, hypotension, hypoventilation, hypercapnia [endocrine-abstracts.org]

  – Sx of hypothyroidism ( weight gain, cold intolerance, constipation, hair loss …) – Hypothermia (often profound-even down to 27 Celsius) – AMS (coma not common- more likely to see lethargy and confusion) -Respiratory sx ( hypoventilation ->hypoxia/hypercapnia [dailyem.wordpress.com]

• Glomerular Filtration Rate Decreased

  Water retention and hyponatremia occurs secondary to reduced glomerular filtration rate, decreased delivery to the distal nephron [ 15 ], and excess vasopressin [ 16, 17 ] ( Figure 1 ). Pathogenesis of myxedema crisis. [ncbi.nlm.nih.gov]

Patients affected by myxedema coma should receive intensive care to carefully monitor the progress of the disorder. They might show signs of hypercapnia or hypoxia that have to be treated with mechanical ventilation. The cardiovascular status too should be carefully checked trough ECG, paying attention to exclude myocardial infarction, monitor blood pressure and avoid pressor agents and inotropes which cause arrhythmias.

Thyroid should immediately treated with intravenous thyroid replacement, even though a harsh controversy exists over what combination of thyroid hormones has to be taken into consideration, T4 alone, T4 combined with T3, or T3 alone. In general, clinicians tends to treat adults with T4 alone, with an initial dose of intravenous T4 of 100-500 micrograms, subsequently followed by a dose of 75-100 micrograms until patients are able to take oral replacements. In younger patients, instead, clinicians tend to administer T4 combined with T3, especially when the cardiovascular risk is low.

Since many patients affected by myxedema coma might develop infections, a treatment based on brad-spectrum antibiotics is strongly recommended. Furthermore, they might also develop adrenal insufficiency secondary to hypopituitarism, which should be treated with a dose of 100 mg of hydrocortisone taken every 8 hours.

The prognosis largely depends on the general conditions of the patients and the presence of other possible pathological disorders. However, the mortality rate appears to be quite high, even when patients have received proper treatment. The prognosis improves when myxedema coma has been diagnosed very early and the patients have undergone presumptive thyroid hormone replacement as well as hydrocortisone-based therapy with related supportive care [1].

Myxedema coma usually appears in subjects who are already affected by a long-lasting and untreated form of hypothyroidism, which is the baseline condition out of which the disorder can manifests itself. In this situation myxedema coma is triggered by a series of other factors which start the crisis. These triggering factors can include infections, especially those affecting lungs and kidneys, heart failure, stroke, trauma, some types of surgery, and drug therapies. The crisis can also be started by the failure of the patient to take the prescribed thyroid medications.

Myxedema coma is around four times more common in women than men, a characteristic that underlines the high incidence and prevalence of hypothyroidisms in the female population, especially those aged over 50. In any case, the disorder almost exclusively occurs in patients older than 60 years of age, especially in those communities characterized by high levels of iodine deficiency, such as some population living in isolated and mountain regions of Asia, Africa and South America. Being much more frequent in winter months [1] [7], the conditions has also a seasonal variation that might be connected with the two classical hypothyroidism signs of age-related loss of temperature sense and decreased heat production.

As previously mentioned, myxedema coma is particularly common in those with long-lasting hypothyroidism, frequently undiagnosed or not properly treated because of a lack of efficient monitoring or poor compliance of the patients to follow the correct therapy. Mortality remains very high, between 25% to 50%, even when patients receive appropriate medical intervention [8].

There is no data suggesting the existence of a race-related epidemiological difference. However, the frequency increases with age [9], even though this tendency is not sufficient to rule out the occurrence of episodes in young adults. Other factors fostering the occurrence of episodes include hypoglycemia, infection, trauma, hemorrhage or a change in the medication prescribed.

Myxedema coma is a form of decompensated hypothyroidism which develops after the occurrence of an additional stress, where the body is no longer capable of adapting and fails to maintain homeostasis [10]. For example, peripheral vasoconstriction occurs in concomitance with reduced metabolic rate and oxygen consumption, to maintain core body temperature. If this fails to occur the body temperature can no longer be preserved. This condition ends up affecting all organs of the body, including heart, lungs, kidneys, gastrointestinal tract and even brain. Obviously, the crisis occurs much more frequently in elderly, who are weaker than younger subjects and much more prone to systemic organic failures.

Subjects with a history of hyperthyroidism are at high risk of developing myxedema coma, and are advised to have the TSH levels checked each year. They should also be aware that they might experience other episodes of myxedema coma in the future and therefore should understand how to recognize the signs of this disorder, even by receiving an appropriate training. Patients are also recommended to constantly comply with the therapy and the administration of the drugs prescribed and have the thyroid function frequently monitored.

The term myxedema also refers to two different dermatological conditions caused hypothyroid and hyperthyroid states. Myxedema coma (MC), instead, refers to the state of decompensated hypothyroidism, seen as an endocrine emergency affecting the entire body [1] [2] [3] [4]. Very rare and potentially fatal [5], this disorder not necessarily involves the occurrence of a comatose state or shows the classical skin changes of myxedema. This is the reason why many experts prefer to refer to the condition as myxedema crisis.

Myxedema coma frequently turns out to be difficult to diagnose and treat successfully, a problem that underlies the high mortality of 50% associated with it [6]. In fact, patients might have the laboratory values of a normal hypothyroid state, but might develop myxedema coma after experiencing a stressful event such as infection, myocardial infarction or stroke. Mainly affecting the elderly with long-lasting and untreated hypothyroidism, the primary signs include altered mental status, low body temperature, low blood sugar and low blood pressure.

Myxedema coma (MC) is an extreme, uncommon and life-threatening manifestation of hypothyroidism characterized by a marked and general decompensation. The term myxedema also refers to different dermatological conditions which might appear with disorders of the thyroid gland. Very rare and potentially fatal [5], myxedema coma not necessarily involves the occurrence of a comatose state or shows the classical skin changes of myxedema. This is the reason why many experts prefer to call it as myxedema crisis.
The condition frequently appears in subjects who are already affected by a long-lasting and untreated form of hypothyroidism. In this situation myxedema coma may be triggered by a series of other factors which start the “crisis”. These triggering factors include infections, especially those affecting lungs and kidneys, heart failure, stroke, trauma, some types of surgery, and drug therapies. The crisis can also be started by the failure to take the prescribed thyroid medications.

Comatose state does not necessarily occurs in every myxedema coma episode, but certainly it characterizes the worst cases. The usual signs instead, which can be typically observed in all cases include weight gain, fatigue, constipation, cold intolerance, coarsened hair, deepened voice and dry, pale and cool skin, facial swelling, low body temperature (less than 35.5 C°), slow heart rate, slow pulse and confusion.

Myxedema coma is around four times more common in women than men, especially in those aged over 50. The prognosis largely depends on the general health and the presence of other possible pathological disorders. However, the mortality rate appears to be quite high, even with proper treatment.

Subjects with a history of hyperthyroidism are at high risk of developing myxedema coma, and are advised to have the TSH levels checked each year. They should also be aware that they might experience other episodes of myxedema coma in the future and therefore should understand how to recognize the signs of this disorder, even by receiving an appropriate training. Patients are also recommended to constantly comply with the therapy and the administration of the drugs prescribed and have the thyroid function frequently monitored.

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