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].

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.

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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