Continuing Education Activity

Myxedema is a term for severely advanced hypothyroidism that is also used to refer specifically to the associated skin changes (nonpitting edema or swelling of the skin and soft tissues, particularly in the face, hands, and legs). Myxedema coma represents the most severe, life-threatening manifestation of hypothyroidism, characterized by altered mentation, multiorgan dysfunction, and high mortality rates despite advances in intensive care. Precipitating factors such as infection, hypothermia, surgery, trauma, or certain medications can overwhelm compensatory mechanisms in hypothyroid patients, triggering this crisis. This course reviews the prompt recognition of myxedema coma, the comprehensive evaluation of thyroid function, and the rapid intervention with intravenous levothyroxine and hydrocortisone, which remain critical to improving outcomes. Given its rarity and complex pathophysiology, myxedema coma demands an interprofessional approach emphasizing early diagnosis and meticulous management to prevent fatal complications.

This activity explores the pathophysiology, clinical manifestations, diagnostic evaluation, and management of myxedema coma. Participants will also gain an in-depth understanding of recognizing subtle presentations, identifying precipitating factors, and implementing timely interventions to improve patient outcomes, as well as intensive care management and individualized hormone replacement strategies. This activity for healthcare professionals is designed to enhance the learner's competence in identifying myxedema coma, performing the recommended evaluation, and implementing an appropriate interprofessional management approach when caring for patients with severe hypothyroid emergencies.

Objectives:

• Identify the clinical features associated with myxedema coma.
• Apply evidence-based guidelines for the timely diagnosis of myxedema coma.
• Implement appropriate therapy to stabilize critically ill patients affected by myxedema coma.
• Coordinate interprofessional care among team members in the management of myxedema coma to optimize patient outcomes.

Introduction

Myxedema coma represents a rare and severe complication of hypothyroidism characterized by multiorgan dysfunction and altered sensorium that can progress to a fatal outcome. Patients with hypothyroidism develop numerous physiologic adaptations to compensate for thyroid hormone deficiency. Stressors (eg, infection) frequently disrupt these compensatory mechanisms, precipitating myxedema coma. This condition may serve as the initial manifestation of any type of hypothyroidism, regardless of its underlying cause.[1] Despite advances in early diagnosis and intensive treatment, reported mortality rates vary widely, ranging from 20% to 25% to as high as 60%. A comprehensive review of studies published between 2004 and 2024 identified an overall mortality rate of 38.8%, with shock and multiorgan failure accounting for most deaths.[2]

The term myxedema commonly describes both severe hypothyroidism and myxedema coma, yet it also refers specifically to the skin and soft tissue edema associated with hypothyroidism.[3] The phrase myxedema coma remains somewhat misleading, as patients rarely exhibit classic nonpitting edema and are not in a coma. The hallmark clinical feature involves progressive deterioration in mental status.

Effective management of myxedema coma requires a high index of suspicion, rapid recognition, prompt intensive care admission, and treatment with intravenous levothyroxine and hydrocortisone.[4][5] Evaluation should include a detailed history of thyroid dysfunction, thyroid hormone use, adherence to prescribed medication, prior thyroid surgery, and exposure to drugs known to influence thyroid function.[6]

Etiology

Disruption of homeostatic mechanisms in patients with hypothyroidism leads to the development of myxedema coma. Numerous factors can precipitate this condition, with the most significant contributors including:

• Infections (most common precipitating factor): urinary tract infection, pneumonia, viral infections, influenza
• Cold weather [3]
• Covid infection (has been documented in more recent years) [7][8]
• Burns, carbon dioxide retention
• Hypothermia and hypoglycemia [3]
• Hypoxemia and cerebrovascular accidents [9]
• Drugs, eg, amiodarone,[10][11] lithium,[12] sedatives, tranquilizers, anesthetics,[13] opioids, phenytoin, rifampin, diuretics, beta-blockers (given the slow drug metabolism in patients with hypothyroidism, these patients have a risk of an overdose when anesthetics and tranquilizers are needed) [3]
• Anti-TNF therapy (case reports of these agents causing myxedema have been documented in the literature) [14]
• Immunotherapy use, eg, CTLA-4 and PD-1 immune checkpoint inhibitors [15]
• Congestive heart failure 
• Gastrointestinal bleeding
• Surgery (given the effect on the pituitary-thyroid axis with decreased thyroid hormone secretion after surgery in response to stress) [16][17]
• Trauma
• Stroke [3]
• Diabetic ketoacidosis (DKA), shown in a case report to precipitate myxedema coma in a patient after total thyroidectomy [18]

Epidemiology

The precise incidence and prevalence of myxedema coma remain uncertain. Some authors estimate an incidence of approximately 0.22 per 1,000,000 individuals annually in the Western world, while epidemiological data from other regions remain limited.[6] A systematic analysis of over 500 published cases between 2004 and 2024 reported an estimated incidence of 0.12 per million per year, representing 0.00016% of all hypothyroid patients. Hospitalized patients demonstrated a higher incidence, accounting for 0.0034% of cases.[2] Myxedema coma affects females more frequently, comprising 80% of reported cases, paralleling the higher prevalence of hypothyroidism in women, which occurs about 4 times more often than in men.[19] Individuals older than 60 years face a greater risk of developing myxedema coma.[20] The condition occurs more often during winter months, accounting for roughly 90% of cases, largely due to hypothermia commonly present in these patients.[21] Reduced heat production from hypothyroidism and age-related decline in thermoregulation explain this seasonal trend.[22]

Pathophysiology

Thyroid Gland Anatomy and Hormone Production 

The thyroid gland begins development during the fourth gestational week as an endodermal thickening on the floor of the primitive pharynx. Its final position lies in the anterior inferior visceral compartment of the neck, deep to the omohyoid, sternohyoid, and sternothyroid muscles. The gland is encased in the pretracheal fascia and closely associated with the pharynx, trachea, esophagus, and recurrent laryngeal nerve.[23] The thyroid consists of two lobes connected by an isthmus, and approximately 40% of the population exhibits a pyramidal lobe extending upward from the isthmus. The gland produces 2 primary hormones, thyroxine (T4) and triiodothyronine (T3), which regulate whole-body metabolism. A complete absence of these hormones can reduce metabolism by 40% to 50%, whereas full secretion can increase it by 60% to 100%.[24]

Thyroid hormone production occurs predominantly in the follicles lined by cuboidal epithelial cells. These follicles secrete colloid composed of thyroglobulin, which contains approximately 30 molecules of T4 and a smaller number of T3 molecules. The metabolically active hormones include 93% T4 and 7% T3, with T3 approximately four times more potent than T4. Most T4 undergoes conversion to T3 within peripheral tissues. T4 has a half-life of 7 days, whereas T3’s half-life is about 1 day. Thyroid hormones bind to transport proteins, including thyroxine-binding globulin, transthyretin, and albumin. Adequate thyroid hormone production requires at least 50 mg of iodine per year or 1 mg per week.[25]

Iodine is concentrated within the thyroid cell by a sodium-iodide symporter that pumps 1 iodide molecule and 2 sodium ions. The serum thyroid-stimulating hormone (TSH) level highly influences the activity of this symporter. A peroxidase enzyme then oxidizes iodide ions to iodine.[26] Organification then occurs by binding iodine to the amino acid tyrosine located within the thyroglobulin molecule. Thyroglobulin is stored in the thyroid gland and contains approximately 30 molecules of T4 and a few molecules of T3. In the complete absence of thyroid hormone production, the thyroid gland contains enough reserves to last about 2 to 3 months.[26]

Physiologic Effects of Thyroid Hormone

The thyroid hormone influences virtually all cells in the body by activating or repressing a variety of genes after binding to thyroid hormone receptors. Approximately 90% of the intracellular thyroid hormone that binds to and influences cellular function is T3, which has been converted from T4 by the removal of an iodide ion. The thyroid hormone receptors associated with the DNA within the target genes are bound to retinoid X receptors at specific thyroid hormone response elements. Once bound, transcription begins, and hundreds of new intracellular proteins, mostly enzymes, are produced. A particular gene of importance is the gene that regulates the expression of calcium ATPase, which is especially important in maintaining efficient cardiac output.[27] 

Moreover, thyroid hormones have nongenomic effects on cells, including the regulation of ion channels and oxidative phosphorylation. These effects may be mediated by thyroid hormone binding to the plasma membrane, cytoplasm, and cellular organelles. Other effects of thyroid hormone include increased Na-K-ATPase activity, increased carbohydrate metabolism, increased free fatty acids (decreased cholesterol, phospholipids, and triglycerides), increased vitamin requirements due to increased enzymes that use vitamins as cofactors, and overall increased metabolism. Given that thyroid hormone is responsible for a vast majority of bodily functions at the genetic and cellular levels, the extreme absence of this hormone, as seen in myxedema coma, can clearly be seen to be associated with a high mortality rate and a broad spectrum of presenting symptoms.[28]

Myxedema coma remains a potentially fatal complication, with mortality reduction heavily dependent on prompt diagnosis.[9] Identifying precipitating factors is essential. Most patients present with hypothermia rather than fever,[29] although minimal hypothermia may mask underlying infection, warranting investigation.[22] Certain medications, including lithium and amiodarone, have been repeatedly reported to precipitate myxedema coma by inhibiting thyroid hormone release.[30] Lithium suppresses cAMP production in response to TSH and can exaggerate TSH response to TRH.[31] Amiodarone blocks thyroid hormone entry into peripheral tissues, inhibits 5’-deiodinase, disrupts T4-to-T3 conversion, and releases excess iodine.[32] Additional precipitating factors include hypoglycemia, hypoxemia, and hypercapnia, which may occur secondary to myxedema coma itself.

Organ System-Specific Pathologic Manifestations

Several pathophysiological changes are noted to occur in the following organ systems.

Cardiac manifestations

Diastolic hypertension is one of the cardiovascular compensatory mechanisms in hypothyroidism. Hypothermia and decreased respiratory drive cause peripheral vasoconstriction, resulting in loss of protective mechanisms and development of hypotension. Common cardiovascular symptoms include hypotension, shock, arrhythmia, and heart block. Myxedema causes decreased myocardial contractility and reduced cardiac output, which leads to hypotension.[33] Bradycardia, flattened T waves, low voltage, bundle branch blocks, and complete heart blocks are common electrocardiogram (ECG) findings.[34] Low voltage on ECG can be representative of pericardial effusion due to the accumulation of fluid rich in mucopolysaccharides, meriting investigation.[35] Fatal arrhythmias are important to recognize in myxedema as well as chronic hypothyroidism.[9] QT interval prolongations have been shown in case studies to lead to “torsades de pointes,” which resolves with treatment of myxedema. Myocardial infarction should be ruled out, as aggressive T4 replacement may precipitate and increase the risk of myocardial infarction.[36][37] Moreover, refractory cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation and, ultimately, heart transplantation can occur in severe cases.[38][36]

Neurological manifestations

The clinical course of myxedema is commonly a slow progression to coma. Typically, patients do not present with coma, especially in the early phase, but instead more commonly present with lethargy. Hence, the name "myxedema coma" can be misleading. Other findings may include depression, disorientation, decreased deep tendon reflexes, psychosis, slow mentation, paranoia, and poor recall.[39] One case describes a rare presentation of a patient with status epilepticus.[40] Lumbar punctures, which are usually performed to investigate underlying causes and exclude infections, can show increased pressure and a high protein count in these situations, mostly attributable to increased meningeal permeability, increased cerebral blood flow, and decreased metabolism.[41]

Respiratory manifestations

Hypoventilation in myxedema coma is due to impaired hypoxic and hypercapnic ventilatory response and the associated diaphragmatic muscle weakness.[42] The primary cause of coma in myxedema appears to be due to respiratory depression due to decreased response to hypercapnia.[34] Furthermore, swelling of the tongue and vocal cords leads to obstructive sleep apnea, contributing to respiratory failure. Another contributing factor is a reduction in tidal volume due to pleural effusion or ascites.[43]

Gastrointestinal manifestations

Myxedema coma commonly causes abdominal pain, nausea, vomiting, ileus, anorexia, constipation, and ascites.[44] Ileus is particularly important because this complication can lead to megacolon. Although uncommon, ascites has also been rarely reported in cases of myxedema. These gastric complications may also impair the absorption of oral medications. Gastrointestinal bleeding can occur as myxedema has a higher risk of bleeding due to coagulopathy-related complications.[45][46]

Renal and electrolyte manifestations

Typical findings in myxedema coma are hyponatremia and decreased glomerular filtration rate.[47] Hyponatremia occurs mainly due to decreased water transport to the distal nephron.[48] Other causes can be an increase in antidiuretic hormone.[49] Hyponatremia is also a key factor in the patient’s altered mental status and the development of a coma.[50] Urinary sodium excretion is increased or normal. Urinary osmolality elevates relative to plasma osmolality.[51] Patients may also have bladder atony, causing urinary retention.

Hematologic manifestations

Patients with myxedema coma have an increased risk of bleeding due to an acquired von Willebrand syndrome type 1 and a decrease in coagulation factors V, VII, VIII, IX, and X.[52] This bleeding risk is unlike that of those with only mild hypothyroidism, which, conversely, causes a hypercoagulable state. Cases have shown that acquired von Willebrand syndrome is reversible with T4 therapy.[53]

History and Physical

Clinical History

Patients with myxedema coma most often present to emergency services with altered mental status and hypothermia, frequently below 95.9 °F (35.5 °C). Prognosis worsens as body temperature declines.[54] The absence of mild diastolic hypertension in severely hypothyroid patients may signal impending myxedema coma.[55] However, an altered mental status can make obtaining a definitive history challenging. Critical historical details include any previous thyroid dysfunction, thyroid medication dosage, adherence to therapy, prior thyroid surgery, and use of drugs affecting thyroid function.

Physical Examination Findings

A rapid, thorough physical examination is essential, as findings, eg, absent palpable thyroid tissue, goiter, sparse hair, nonpitting edema, surgical neck scars, or dry skin, help confirm thyroid involvement. Older adult patients may exhibit atypical presentations, including reduced mobility.[56]

Key examination findings of clincal examination include altered mentation, the most common presentation, occurring in 88.9% of patients with confirmed myxedema coma.[2] Altered mentation may appear subtly as depressed affect, apathy, decreased intellectual capacity, confusion, short attention span, or disorientation, with psychosis and coma occurring rarely.[57] Additionally, all patients with reduced alertness should be screened for depression.[58]

Additional features associated with myxedema may include hypoventilation, sleep apnea, and variable hypothermia; some patients remain normothermic. Skin changes typically include dry, cool, and doughy skin, nonpitting edema, and puffiness, often accompanied by alopecia. Other signs include decreased mobility, delayed reflex relaxation, diastolic hypertension progressing to hypotension, bradycardia, bladder dystonia with distention, abdominal distention, paralytic ileus potentially causing megacolon, and fecal impaction, highlighting the importance of routine rectal examination.

Evaluation

A high index of clinical suspicion for myxedema coma is important for timely diagnosis. As discussed above, patients who present with myxedema will most likely be women in the winter months with a history of thyroid disorders and a precipitating illness. The 2 most common findings will be altered mental status and hypothermia, along with common findings of hypothyroidism. Other common signs include hyponatremia, hypotension, bradycardia, and hypoventilation. In severe hypothermia, cardiac arrest can occur.[59][60][2][3] 

Laboratory Studies

In primary hypothyroidism, laboratory findings typically reveal severely reduced or undetectable levels of serum total thyroxine (TT4), free thyroxine (FT4), and free triiodothyronine (FT3), accompanied by elevated TSH. The most common underlying cause involves primary thyroid failure; however, secondary, tertiary, and sick euthyroid conditions should also be considered in the differential diagnosis.[59] In euthyroid sick syndrome, TSH elevation may not reach expected levels. A small subset of patients may present with central hypothyroidism, in which TSH appears inappropriately low. Differentiating central from primary hypothyroidism requires evaluation of other pituitary-associated hormones, which typically decline in central hypothyroidism.[29][61]

The following laboratory abnormalities are associated with myxedema coma:

• Anemia (either normocytic or macrocytic anemia) and leukopenia [62]
• Elevated creatinine phosphokinase (can lead to misdiagnosis of myocardial infarction) [63]
• Elevated transaminases
• Hyperlipidemia (due to the inhibition of the lipoprotein lipase enzyme)
• Hypoglycemia (due to downregulation of metabolism)
• Hyponatremia with low serum osmolarity and elevated creatinine (increased antidiuretic hormone with a decreased ability of the kidneys to excrete water) [48] 

Additional Diagnostic Studies

Other studies required to evaluate suspected myxedema coma include:

• Septic workup to rule out infection, including cultures and chest x-ray [64]
• ECG (can show bradycardia with nonspecific changes, decreased voltage, variable block, prolonged QT interval, torsades de pointes, and sustained polymorphic ventricular tachycardia) [65][37]
• Arterial blood gas (can show hypoxia, hypercapnia, and respiratory acidosis)
• Echocardiogram (if cardiomegaly is present on imaging studies, further investigations to rule out pericardial effusion are necessary)
• Neurological investigations, eg, lumbar puncture (usually show elevated protein with nonspecific EEG changes)[65]
• Brain magnetic resonance imaging (MRI) and pituitary laboratory workup (recommended for suspected central hypothyroidism and panhypopituitarism) [66]

A retrospective study in 2014 proposed a diagnostic score for 14 patients with myxedema coma and 7 without myxedema coma; a score of 60 or greater in the proposed scoring system was potentially diagnostic. Lower scores between 45 and 59 demonstrate a risk of developing myxedema coma. The scoring system consisted of alterations of thermoregulatory, central nervous, cardiovascular, gastrointestinal, and metabolic systems, and the presence or absence of a precipitating event.[67] A new proposed diagnostic criterion was suggested by Zhang et al in 2025. Prerequisites for diagnosis include laboratory results showing a reduced FT4 or FT3 with either elevated TSH in primary hypothyroidism or low or normal TSH in secondary hypothyroidism (see Table. Proposed Diagnostic Criteria).[2]

Table

Table. Proposed Diagnostic Criteria.

Treatment / Management

Since myxedema coma has a high mortality rate of up to 60%, all patients require admission to the intensive care unit.[68][69] A higher mortality has been documented in older adult females, as well as in patients who present with cardiac arrhythmias, persistent hypothermia, reduced consciousness, and sepsis.[70] Interestingly, patients admitted during the weekend had an all-cause mortality rate higher than those admitted on regular weekdays.[71] 

Management of Precipitating Factors

Treating myxedema coma is a multisystem challenge. Identifying any precipitating factor is essential.

Respiratory and airway management

Respiratory and airway management is a critical component of patient care. Frequent arterial blood gas analysis should be performed to monitor for hypercapnia and hypoxemia. Most patients will require mechanical ventilation as the altered mental status leaves them more prone to aspiration. Moreover, airway obstruction may occur due to laryngeal myxedema. Patients should not stop receiving ventilator support until the resolution of both hypercapnia and hypoxemia, as well as the patient regaining consciousness. Additionally, assessment for any pneumonia with imaging is needed to ensure appropriate treatment as a precipitating factor.[72] One should also initiate fluid resuscitation while monitoring sodium and slow rewarming to avoid further hypotension. Workup for infectious etiologies, including lumbar puncture, blood and urine cultures, and empiric antibiotic use, along with appropriate imaging and indicated interventions, is considered necessary.[73]

Hypothermia and hemodynamic stability

Hypothermia should be managed with warming blankets and increasing the room temperature. Caution in warming the patient is advised, as this will cause peripheral vasodilation and may lead to hypotension and shock. As the patient receives thyroid replacement treatment, the hypothermia will slowly resolve. Hypotension requires careful management due to multiple issues commonly present concurrently, eg, hyponatremia, hypoglycemia, and hypothermia, and as previously stated, rapid rewarming of the patient will increase vasodilation, worsening hypotension. Therefore, this action necessitates the use of fluids to maintain hemodynamic stability. If hypotension is refractory to intravenous (IV) fluid resuscitation, then vasopressors should be initiated until levothyroxine has time to become effective.

Hypoglycemia and hyponatremia

If hypoglycemia is present, 5% to 10% dextrose with half-normal saline should be administered carefully. The dilemma occurs if the patient presents with hyponatremia as well. Hypotonic fluids should be avoided. Low sodium can precipitate an altered mental status, and correcting the deficiency is vital. A careful balance between fluid restriction and the need for fluids must be maintained. A central venous line is also recommended.[48] If hyponatremia is severe (below 120 mmol/L), careful administration of 3% sodium chloride, along with an IV bolus of furosemide to promote diuresis, is needed. A 4 to 6 mmol/L increase in serum sodium concentration is shown to correct many neurological symptoms. Slow correction is vital as overcorrection increases the risk for osmotic demyelination syndrome. Current research suggests that the correct rate should not exceed 6 to 8 mmol/L in 24 hours. Once serum sodium levels rise above 130 mmol/L, fluid restriction should be sufficient to correct the hypernatremia.[74]

Thyroid Hormone Therapy

Prompt initiation of thyroid hormone therapy is of paramount importance when myxedema coma is highly suspected, even before having thyroid hormone results back (even though results usually come back quickly in most clinical institutions).[75] A delay could increase the patient's mortality and morbidity.[76] Hydrocortisone is recommended to be administered prior to thyroid hormone therapy, especially if the patient is hypotensive, to avoid adrenal crisis; suggestions are that levothyroxine will increase cortisol metabolism, and hypothyroidism may mask an underlying adrenal insufficiency.[77] A recommended course of therapy, if possible, is to draw blood for random cortisol, TSH, FT4, FT3, and administer hydrocortisone starting with a 100 mg IV initiating dose (total 200 to 400 mg daily), which can be stopped or weaned down based on cortisol when blood levels are back, and hypotension resolves.[78] The administration of IV levothyroxine should follow. Repeat TSH, FT4, and FT3 every 24 to 48 hours is recommended for dose adjustment.[76] 

According to the most recent American Thyroid Association (ATA) guidelines, the recommended initial loading dose of levothyroxine is 200 to 400 µg IV once, with a lower dosage recommended for older adults or in the presence of underlying cardiac disease or arrhythmia. Subsequently, the dosage should be reduced to 1.6 µg/kg/day, with a 75% reduction when given IV as the preferred route, for patients who may not be able to tolerate oral intake and whose absorption could be impaired secondary to intestinal motility impairment and edema.[75] The optimal levothyroxine dosage is still debated, especially as a higher dosage may cause harm, particularly in older adult patients or in patients with underlying cardiac disease or arrhythmia.[4]

Clinicians should also consider adding liothyronine as a loading dose of 5 to 20 µg, followed by 2.5 to 10 µg IV every 8 hours if no response to the initial levothyroxine treatment is noted within 24 hours (weak recommendation, low-quality evidence). Caution should be exercised with patients with a history of underlying heart disease or cardiac arrhythmia since a case series showed increased adverse outcomes with higher doses of liothyronine therapy.[76] Another controversy is whether liothyronine is appropriate for patients whose mental status does not improve in 24 to 48 hours after administration of levothyroxine or with undetectable FT3 levels. The conversion of FT4 to FT3 at the cellular level will be impaired in severely ill patients and those on steroids, which is well known.[76] However, this impaired conversion may sometimes serve as a protective mechanism, slowing metabolism in severely ill patients to preserve organ function. Whether this phenomenon can be extrapolated to patients with myxedema coma is still controversial.[79] However, properly dosing liothyronine with caution is essential, as the high levels have been shown to correlate with increased mortality.[68]

In countries and centers where IV levothyroxine is not available or not affordable, an oral levothyroxine regimen has been used as an alternative in myxedema coma.[80][81] A retrospective study done in India (14 patients) reported a loading oral dosage of levothyroxine 300 to 500 μg (dosage variable based on history of coronary artery disease and ejection fraction), followed by taper over the next 3 to 5 days, which has been used with successful results (13 out of 14 patients survived on that regimen).[81] A case report in 2017 divided the oral levothyroxine dose into 200 µg every 8 hours, administered as 5 consecutive doses (total dosage of 1 mg), resulting in significant restoration of thyroid function and clinical improvement within 48 hours of treatment initiation.[82] Another case report in 2019 treated the patient with a combination of levothyroxine 200 µg and liothyronine 50 µg for 5 days, with successful improvement in the patient's condition; thus, some reports recommended starting with 200 to 300 µg levothyroxine and 10 to 25 µg liothyronine as an alternative initial treatment.[83]

While optimal levels for serum TSH and thyroid hormones are not well defined in these circumstances, failure of TSH to trend down or for thyroid hormone levels to improve could be considered indications to increase levothyroxine therapy or add liothyronine therapy. In contrast, high serum FT3 is an indication to decrease therapy, given safety concerns. An in vitro study in rats by Mooradian et al concluded that aging is associated with reduced responsiveness to T3-stimulated upregulation of beta-adrenergic receptor number in synaptosomal membranes, and this effect did not improve with higher doses of liothyronine.[79]

The severity of myxedema coma should not rely solely on higher levels of TSH, as it does not always correlate, especially in cases that secondary hypothyroidism due to suppression of the hypothalamic-pituitary axis in critically ill patients, a slower response in older adults, or purely secondary hypothyroidism from pituitary causes may occur. The expectation is that serum FT4 will normalize within 4 days of starting therapy.[84]

Differential Diagnosis

Differential diagnoses are based on presenting clinical features. For example, the differential diagnoses of altered mental status or coma include:

• Sepsis
• Shock
• Stroke
• Drug overdose
• Diabetic ketoacidosis
• Seizure
• Hypothermia [85]

Prognosis

The prognosis for myxedema coma is challenging to establish due to the small number of cases reported. The mortality rate is variable, with some reports as high as 60% and others as low as 20% to 25% in the presence of advanced intensive support care.[86] The overall mortality rate, based on a recent report summarizing publications from 2004 to 2024, was 38.8%. Shock and multiorgan failure were the most common causes of death.[2] Poor prognosis is likely related to advanced age, bradycardia, and persistent hypothermia.[68]

Complications

If left untreated, myxedema coma is fatal.[9] Complications of myxedema include coma, respiratory failure, myocardial ischemia, sepsis, shock, and gastrointestinal hemorrhage.[29]

Consultations

An endocrinology consultation becomes essential once myxedema coma is suspected. Early specialist involvement supports timely diagnostic confirmation and appropriate thyroid hormone replacement management.

Patients presenting with arrhythmia, respiratory distress, or multiorgan failure require coordination of care through an interprofessional team that includes cardiology, pulmonary, intensive care, and endocrinology specialists. Collaborative management enhances treatment precision, stabilizes critical functions, and improves overall outcomes.

Deterrence and Patient Education

Deterrence and patient education focus on preventing myxedema coma through early recognition, adherence to thyroid hormone therapy, and prompt management of hypothyroidism. Patients must understand the importance of lifelong thyroid replacement and regular monitoring of thyroid function to maintain hormonal stability. Education should emphasize recognizing symptoms such as fatigue, cognitive decline, cold intolerance, and weight gain, which may indicate inadequate thyroid control.

Additionally, clinicians should counsel patients on avoiding abrupt discontinuation of medication and recognizing potential triggers, eg, infections, cold exposure, sedatives, and drugs that interfere with thyroid metabolism, including lithium and amiodarone. Patients should also be advised of the importance of performing thyroid function monitoring, especially after starting certain medications, eg, amiodarone, lithium, and anti-TNF agents. Ongoing communication between patients and healthcare practitioners fosters early intervention and significantly reduces the risk of progression to myxedema coma.

Enhancing Healthcare Team Outcomes

Myxedema coma represents a rare but often fatal manifestation of severe hypothyroidism that results from extreme deficiency of thyroid hormone. The condition involves multiple organ dysfunction and altered mental status, typically triggered by infection, cold exposure, or medication nonadherence. Rapid diagnosis and intervention are crucial to survival, with mortality remaining high despite intensive care.[29] Management focuses on airway protection, hemodynamic stabilization, intravenous administration of thyroid hormone and corticosteroids, and treatment of precipitating causes. Early endocrinology consultation and interprofessional coordination are essential to improve outcomes and reduce complications.

Effective management of myxedema coma relies on a skilled interprofessional team. Physicians, advanced practitioners, and endocrinologists lead diagnostic evaluation, guide thyroid hormone therapy, and oversee stabilization efforts in the intensive care unit.[22] Nurses play a vital role in the continuous monitoring of temperature, cardiovascular status, and respiratory function, promptly reporting deviations to the team. Pharmacists ensure appropriate dosing, monitor for drug interactions, and coordinate with clinicians regarding nutritional and parenteral therapy. Respiratory therapists assist with ventilation, while dietitians design enteral or parenteral nutrition plans for patients unable to eat. Ongoing communication across all disciplines enhances patient safety, promotes timely adjustments in therapy, and ensures cohesive care delivery. After discharge, clinicians and pharmacists educate patients on lifelong adherence to thyroid hormone therapy, the importance of regular monitoring, and the avoidance of medications that may impair thyroid function, reinforcing patient-centered continuity of care.

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Disclosure: Ghada Elshimy declares no relevant financial relationships with ineligible companies.

Disclosure: Venu Chippa declares no relevant financial relationships with ineligible companies.

Disclosure: Catherine Anastasopoulou declares no relevant financial relationships with ineligible companies.

Disclosure: Ricardo Correa declares no relevant financial relationships with ineligible companies.