Myxedema Coma

Myxedema coma is a rare, life-threatening endocrine emergency representing the decompensated state of severe hypothyroidism, characterized by progressive neurocognitive dysfunction, hypothermia, and multiorgan failure.

Also Called / Synonyms

• Myxedema crisis
• Decompensated hypothyroidism
• Severe hypothyroidism with altered mental status
• End-stage hypothyroidism (historical)

Axis Nomenclature: Primary, Secondary, Tertiary

Myxedema coma arises from thyroid hormone deficiency at any level of the hypothalamic-pituitary-thyroid (HPT) axis. The terminology distinguishes the site of defect:

• Primary hypothyroidism (thyroid gland failure) - accounts for the vast majority of cases; TSH elevated, free T4 low.
• Secondary hypothyroidism (pituitary TSH deficiency) - TSH inappropriately low or normal despite low free T4.
• Tertiary hypothyroidism (hypothalamic TRH deficiency) - similar biochemical pattern to secondary but distinguished by dynamic testing. This axis nomenclature is used throughout the article to clarify etiology and guide management .

Classification by Severity: Compensated vs. Decompensated

Hypothyroidism exists on a continuum. In compensated hypothyroidism, gradual physiological adaptation maintains clinical stability despite chronic thyroid hormone deficiency. The transition to decompensated hypothyroidism (myxedema coma) is an acute or subacute loss of homeostatic compensation, typically triggered by a precipitating event such as infection, cold exposure, sedative medications, or myocardial infarction ^[1]B2c. The diagnostic scoring system developed by Popoveniuc et al. operationalizes this distinction:

A score of 60 has 100% sensitivity and 85.7% specificity for myxedema coma ^[3]C4. The odds ratio per score unit increase is 1.09 (95% CI 1.01-1.16) ^[3]C4.

Clinical Significance

Myxedema coma is independently associated with a 6.8% in-hospital mortality rate versus 0.7% for hypothyroid patients without coma (adjusted odds ratio 9.92, 95%; P < 0.001) ^[1]B2c. Mean hospital length of stay is 9.6 days, and total costs exceed $21,000 per admission ^[1]B2c. Recognition of the syndrome and prompt initiation of therapy are critical to reducing this mortality.

Pearl: Myxedema coma is a decompensated state defined by a diagnostic score ≥60 (Popoveniuc criteria), any patient with hypothyroidism and altered mental status, hypothermia, or bradycardia should be considered to have myxedema coma until proven otherwise, and treatment should not be delayed for diagnostic confirmation.

From the definitional framework of the preceding section, the clinician now requires a mechanistic understanding of how a chronically compensated hypothyroid state deteriorates into the life-threatening syndrome of myxedema coma. The hypothalamic-pituitary-thyroid (HPT) axis normally maintains a stable serum T4 and T3 concentration through a negative-feedback loop: low circulating thyroid hormones stimulate thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion, which in turn drives residual thyroid tissue to produce T4. In a patient with long-standing, severe hypothyroidism, this reflex is intact but the gland cannot respond, TSH rises to extreme levels (median 113.9 mIU/L; range 41.9-500.0 mIU/L in a recent ICU cohort ^[7]C4) while FT4 plummets (median 0.11 ng/dL) and FT3 is similarly depressed ^[7]C4. The peripheral tissues are starved of triiodothyronine, disabling the cellular machinery that normally sustains metabolic rate, thermogenesis, and cardiovascular function ^[8]C4[9]D5.

The precipitating event and loss of compensation

Homeostasis is maintained by a fragile balance of reduced metabolic demands and adaptive responses. A precipitating factor, infection, cold exposure, sedative drugs, or systemic inflammation such as IgA vasculitis ^[8]C4, breaks this equilibrium. The stressor increases the demand for thyroid hormone action, but the supply cannot rise. Concurrently, cytokine release (tumor necrosis factor-α, interleukin-2, interleukin-6, interleukin-8) further suppresses peripheral T4-to-T3 conversion and promotes the inactive reverse T3 (rT3), worsening the cellular T3 deficit ^[8]C4. Glucocorticoid administration, if given for a concomitant condition, additionally suppresses TSH secretion and T4→T3 conversion, compounding the deficiency ^[8]C4. The result is a cascade of decompensation across all organ systems.

Stepwise mechanism of decompensation

1. Intracellular T3 deficiency reduces the activity of Na+/K+-ATPase, impairing cellular ion gradients and reducing basal metabolic rate.
2. Hypothermia (temperature <36°C, often <35°C) results from decreased thermogenesis in brown adipose tissue and skeletal muscle ^{[5]C4[7]C4[8]C4}.
3. Cardiovascular collapse: diminished T3 lowers myocardial contractility, heart rate, and stroke volume. In a large cohort, 37.5% of patients had reduced left ventricular ejection fraction (LVEF), 68.6% had abnormal left ventricular global longitudinal strain (GLS), and 66.7% had diastolic dysfunction ^[7]C4. Bradycardia (heart rate <60 bpm) is a hallmark; patients with myxedema coma had a significantly longer PR interval (176.4±37.6 vs 158.3±26.2 ms) ^[7]C4. QTc prolongation occurred in 43.2% of cases, reflecting delayed ventricular repolarization from reduced potassium channel expression ^[7]C4.
4. Respiratory failure: central hypoventilation and decreased chemosensitivity to CO₂ and O₂ lead to type II respiratory failure (hypercapnia and hypoxia) ^[8]C4.
5. Renal and electrolyte disturbances: reduced cardiac output decreases glomerular filtration; impaired free water excretion (due to antidiuretic hormone excess and diminished distal delivery) causes euvolemic hyponatremia ^[10]D5.
6. Neurological dysfunction: altered mental status, progressing to coma, results from cerebral hypoperfusion, hyponatremia, and direct T3 deficiency on neuronal metabolism ^[5]C4[8]C4.

Biochemical signature

The diagnostic laboratory pattern combines an extremely elevated TSH (usually >40 mIU/L) with low FT4 and FT3. However, the case of myxedema coma in a patient with subclinical hypothyroidism (TSH 6.09 mIU/L, FT4 10.7 pmol/L, FT3 2.7 pmol/L) illustrates that the degree of biochemical abnormality does not always correlate with clinical severity, a fall from a higher premorbid set point may be pathogenic ^[5]C4. In the ICU cohort, TSH and FT4 levels did not differ between patients with and without coma, suggesting that tissue-level resistance and the severity of precipitating factors determine the clinical picture ^[7]C4.

Key mediators

• Cytokines: TNF-α, IL-2, IL-6, IL-8 suppress T4→T3 conversion and increase rT3 ^[8]C4.
• β-Adrenergic receptor desensitization: T3 deficiency reduces β-adrenergic responsiveness, exacerbating bradycardia and low-output state ^[7]C4.
• Complement activation in IgA vasculitis may contribute to tissue injury ^[8]C4.

Pearl: In a hypothyroid patient with altered mental status, hypothermia, and bradycardia, do not wait for the TSH result, start empiric thyroid hormone replacement, as the clinical severity may exceed the biochemical degree of hypothyroidism ^[5]C4[8]C4.

Callouts

• high_yield: The classic triad of myxedema coma is hypothermia, altered mental status, and bradycardia. QTc prolongation is the most common ECG finding (>40% of patients) ^[7]C4.
• warning: Glucocorticoid administration can suppress TSH and T4→T3 conversion, potentially worsening hypothyroidism. Always give stress-dose steroids before or simultaneously with thyroid hormone to avoid precipitating adrenal crisis ^[8]C4.

The physiological decompensation described in the preceding section manifests clinically only when a precipitating event overwhelms compensatory mechanisms. The frequency and triggers of such events are defined by the epidemiological profile of myxedema coma.

Incidence and Demographics

Myxedema coma is rare. The estimated incidence is 2.56 cases per 1 million US persons per year ^[14]D5; in Japan, it is 1.08 per million per year ^[17]B2c. A national inpatient database in Japan identified 149 cases among approximately 19 million hospitalizations ^[17]B2c. The condition disproportionately affects older adults, with a mean age of 77 years (SD 12) in the Japanese cohort ^[17]B2c. Female sex predominates: two-thirds of patients are women ^[17]B2c, consistent with the 5:1 female-to-male ratio of hypothyroidism ^[14]D5. Geographic variation follows hypothyroidism prevalence: higher in iodine-sufficient areas of North America and Europe (0.3%-2% overt hypothyroidism) and up to 11% in iodine-deficient regions of Asia ^[14]D5.

Temporal and Seasonal Trends

Seasonal variation is striking. The number of myxedema coma admissions is highest in winter ^[17]B2c, likely driven by cold exposure precipitating decompensation. No clear temporal trend in incidence has been reported, but recognition may be increasing with better awareness and diagnostic coding ^[14]D5.

Risk Factors and Precipitating Events

Myxedema coma is almost always triggered by an acute event in a patient with undiagnosed or undertreated hypothyroidism ^[15]D5. The most common precipitants are infections (especially pneumonia), cerebrovascular accidents, and trauma ^[15]D5. COVID-19 has been identified as a trigger: a 69-year-old woman with preexisting immunotherapy-induced autoimmune thyroiditis developed myxedema coma and died on day 3 ^[11]C4. Other precipitating factors include surgery (e.g., esophagectomy ^[12]C4), cold exposure, medications ( amiodarone , lithium, immune checkpoint inhibitors), and nonadherence to levothyroxine ^[14]D5[15]D5. The table below summarizes the major risk factor categories.

Special Considerations

Infectious triggers. The systematic review of COVID-19 and autoimmune thyroiditis documented one fatal myxedema coma among 20 autoimmune thyroid disease cases ^[11]C4. COVID-19 may precipitate decompensation through cytokine-mediated thyroid injury or direct viral invasion of thyroid cells ^[11]C4. COVID-19 vaccines have been reported to trigger autoimmune thyroiditis, but no myxedema coma cases have been attributed to vaccination ^[11]C4.

Medication-induced. Drugs that impair thyroid hormone synthesis or release, amiodarone, lithium, interferon alfa, and immune checkpoint inhibitors, are well-recognized risk factors ^[14]D5[15]D5. Tyrosine kinase inhibitors can cause destructive thyroiditis ^[14]D5.

Mortality Context

In-hospital mortality is 29.5% in the Japanese database ^[17]B2c and up to 30% in other reports ^[14]D5. Higher age and the need for catecholamines independently predict death ^[17]B2c.

These epidemiological patterns inform the clinical suspicion for myxedema coma, which is discussed in the next section.

Pearl: In any elderly woman with altered mental status and hypothermia during winter, especially with a history of hypothyroidism or recent infection, immediately suspect myxedema coma, the incidence peak in winter and the high mortality demand a low threshold for testing.

From these epidemiological patterns emerges a recognizable clinical syndrome that progresses insidiously over weeks to months before catastrophic decompensation. The transition from compensated hypothyroidism to myxedema coma is often precipitated by infection, cold exposure, sedative drugs, or myocardial infarction ^[18]C4.

Presenting Symptoms

The prodrome includes fatigue, cold intolerance, weight gain, constipation, hoarseness, periorbital edema, and dry skin. Patients or families report progressive lethargy, poor appetite, and bilateral lower extremity edema over weeks ^[18]C4. Acute decompensation is marked by the classic triad: hypothermia (core temperature <35°C, often <32°C in severe cases ^[5]C4[18]C4), altered mental status (lethargy progressing to coma), and bradycardia (heart rate <60 beats/min). Hypoventilation and hypotension are common late findings ^[18]C4.

Neurological Examination Findings

Depressed consciousness ranges from obtundation to coma; Glasgow Coma Scale scores of 5-6 are typical ^[11]C4[18]C4. Deep tendon reflexes show a characteristic delayed relaxation phase (hung-up reflex). Cranial nerve findings may include ptosis ^[13]C4 and, rarely, sudden sensorineural hearing loss ^[19]C4. Choreiform movements have been described during early treatment but resolve with thyroid hormone replacement ^[20]C4. In infants, presenting signs include ptosis, dysphagia, and failure to thrive ^[13]C4.

Cardiovascular Findings

Bradycardia is universal. Examination reveals muffled heart sounds, narrow pulse pressure, and non-pitting edema. Pericardial effusion, moderate in size, is detected in up to one-third of cases and may be visible on chest radiography as cardiomegaly ^{[5]C4[18]C4[19]C4}. Echocardiography confirms the effusion and may show inferior wall hypokinesis ^[18]C4.

Electrocardiographic Findings

Red Flags Requiring Urgent Action

• Core temperature <32°C, indicates severe decompensation; passive rewarming needed ^[5]C4[18]C4
• Heart rate <45 bpm, may precede hemodynamic collapse
• Glasgow Coma Scale <8, airway protection needed
• Hypoventilation (PaCO₂ >45 mmHg), impending respiratory failure
• Pericardial effusion with signs of tamponade, pulsus paradoxus, Kussmaul sign
• Hypotension unresponsive to fluids, consider adrenal insufficiency ^[13]C4

Atypical Presentations

Myxedema coma can present with subclinical hypothyroidism (elevated TSH, normal free T4), highlighting the importance of a low clinical threshold ^[5]C4. COVID-19 infection has been reported as a trigger, with patients presenting with hypothermia, hypotension, and hypoventilation ^[11]C4. Rhabdomyolysis with acute kidney injury and profound sensorineural hearing loss may be the dominant features ^[19]C4. In undiagnosed cases, sudden cardiac arrest from bradyarrhythmia or myocardial infarction can be the first presentation ^[18]C4.

The diagnosis remains clinical, waiting for confirmatory labs risks missing the window for life-saving intervention. The next section details the hormonal workup that confirms the biochemical signature.

Pearl: Atypical presentations such as chorea, sensorineural hearing loss, rhabdomyolysis, or sudden cardiac arrest may delay recognition, a low threshold for thyroid testing in unexplained altered mental status is essential.

In a patient with depressed consciousness, hypothermia, and bradycardia, the diagnosis of myxedema coma must be considered immediately, as laboratory confirmation can take hours. The cornerstone of biochemical diagnosis is the paired measurement of serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4), obtained before any hormone replacement is given ^[15]D5[22]D5. A markedly elevated TSH with a low FT4 confirms primary hypothyroidism as the underlying cause. However, a low TSH with a low FT4 should prompt suspicion for central (secondary) hypothyroidism, though this pattern is far less common in myxedema coma ^[9]D5[22]D5. In rare instances, as reported by Mallipedhi et al, subclinical hypothyroidism with normal FT4 levels can still precipitate the syndrome, underscoring that the diagnosis rests on clinical judgment rather than strict biochemical cutoffs ^[5]C4.

Laboratory Studies

The following table summarises the essential laboratory investigations and their expected findings in myxedema coma. All initial blood work should be drawn before starting treatment.

Dynamic Testing: ACTH Stimulation

Because myxedema coma is frequently accompanied by adrenal insufficiency (either coincident autoimmune disease or pituitary failure), a baseline serum cortisol should be drawn immediately. A cosyntropin (synthetic ACTH) stimulation test should then be performed unless the patient is so unstable that empiric glucocorticoid coverage cannot wait ^[5]C4[9]D5. A normal post-stimulation cortisol peak > 18 µg/dL effectively excludes adrenal insufficiency ^[5]C4[9]D5. If the test cannot be done promptly, administer stress-dose hydrocortisone empirically after drawing the baseline cortisol ^[9]D5[23]C4.

Imaging and Ancillary Studies

No single imaging study confirms myxedema coma, but several help identify precipitating causes and complications:

• Chest radiograph - may show cardiomegaly, pleural effusion (bilateral costophrenic angle blunting ^[18]C4), or pulmonary edema.
• Echocardiography - frequently reveals a moderate pericardial effusion and global hypokinesis ^[5]C4[18]C4.
• Non‑contrast head CT - indicated when altered mental status is disproportionate to metabolic derangement, to exclude intracranial catastrophe.
• Contrast‑enhanced CT of the chest/abdomen - may identify an occult infection (the most common trigger ^[23]C4) or pulmonary embolism.

Electrocardiographic Findings

ECG is a rapid bedside clue. The classic pattern in myxedema coma is sinus bradycardia with low voltage and diffuse T‑wave inversions ^[18]C4. Other findings include QT prolongation and conduction delays. These changes typically reverse with thyroid hormone therapy.

Diagnostic Algorithm

A structured approach to diagnosis is outlined below. Because myxedema coma is a clinical diagnosis, the algorithm emphasises early empiric therapy without waiting for all test results.

Step 1: Clinical recognition (depressed consciousness, hypothermia, precipitating event). Step 2: Immediately draw paired TSH/FT4, serum cortisol, and baseline labs. Step 3: If TSH is elevated and FT4 low, primary hypothyroidism is confirmed; if both are low, consider central hypothyroidism. Step 4: Perform ACTH stimulation test (or give empiric hydrocortisone if unstable). Step 5: Initiate thyroid hormone replacement and supportive care while awaiting detailed laboratory results.

Pitfalls in Diagnosis

• The lab may not reflect the clinical severity. A case of myxedema coma with only subclinical hypothyroidism has been documented - TSH 6.09 mIU/L and FT4 10.7 pmol/L ^[5]C4. Do not dismiss the diagnosis because the numbers are not overtly abnormal.
• Adrenal insufficiency must be ruled out or covered. Starting thyroid hormone without glucocorticoid coverage can precipitate an adrenal crisis ^[9]D5[18]C4.
• Autoantibodies (anti‑TPO, anti‑thyroglobulin) are often elevated in Hashimoto thyroiditis but are not required for diagnosis; they help establish etiology ^[18]C4.

Popoveniuc Diagnostic Criteria

Several scoring systems have been proposed, though none are universally validated. The Popoveniuc criteria assign points for clinical features (altered mental status, hypothermia, cardiovascular instability) and laboratory abnormalities; a score > 60 supports the diagnosis ^[23]C4. These criteria can assist clinical decision‑making but should never delay treatment.

Pearl: If you suspect myxedema coma, start treatment before the lab results return - the mortality of the untreated syndrome far exceeds the risk of hormone therapy, and a normal TSH or FT4 does not reliably exclude the diagnosis ^[1]B2c[5]C4.

Once the diagnosis of myxedema coma (MC) is established, the clinician must rapidly assess the severity of the decompensation to determine the appropriate intensity of monitoring and treatment. Unlike thyroid storm , for which the Burch-Wartofsky scale provides a validated severity score, no equivalent grading system exists for MC ^[2]D5. The current evidence base for risk stratification comes primarily from the National Inpatient Sample (NIS) analysis by Chen et al., which compared MC patients to hospitalized hypothyroid patients without coma (nonMChypo) ^[1]B2c.

Overall Mortality Risk

The in-hospital mortality rate for MC is 6.8% versus 0.7% for nonMChypo (p < 0.001). After adjusted regression, MC independently increased the odds of death nearly 10-fold (aOR = 9.92) ^[1]B2c. This stark difference underscores that the diagnosis of MC itself is the strongest single risk factor for a fatal outcome.

Clinical Predictors of Severity

Several demographic and clinical features were associated with MC in the NIS cohort and should alert the clinician to a more severe presentation:

• Older age - MC patients were significantly older than nonMChypo patients (p = 0.02) ^[1]B2c.
• Seasonal pattern - More admissions occurred in winter compared with other seasons (p = 0.01), suggesting that cold exposure is a frequent precipitant and a marker of severity ^[1]B2c.
• Socioeconomic vulnerability - Public insurance (p = 0.01) and unhoused status (p = 0.04) were overrepresented in MC, likely reflecting barriers to chronic thyroid hormone replacement that predispose to decompensation ^[1]B2c.

Although the NIS study did not provide organ-specific scores, the classic triad of hypothermia, altered mental status, and bradycardia remains the clinical cornerstone for severity assessment. The presence of any of these findings in a hypothyroid patient should prompt immediate consideration of MC, and the number of organ systems involved (CNS, cardiovascular, pulmonary, renal) can be used to gauge urgency.

Resource Utilization and Prognosis

Severity is also reflected in hospital resource use. Mean length of stay for MC was 9.64 ± 0.73 days versus 4.62 ± 0.12 days for nonMChypo (p < 0.001). Total hospital cost was $21,768 ± $1,759 (vs. $8,941 ± $276, p = 0.07) ^[1]B2c. These figures indicate that MC routinely requires intensive care unit admission, mechanical ventilation if consciousness is impaired, and prolonged monitoring.

Need for a Standardized Scoring System

As noted by Ishii, the lack of objective diagnostic tools and grading scales for endocrine emergencies remains a significant gap ^[2]D5. While the NIS data provide population-level risk estimates, they cannot replace a bedside severity score. The Endocrine Society has emphasized the need for precision medicine approaches that individualize risk assessment across the spectrum of thyroid disease severity, from subclinical hypothyroidism to myxedema coma ^[6]D5. Until such a tool is validated, clinicians should rely on the combination of (1) the presence of MC by ICD-10 criteria, (2) the number of organ systems compromised, and (3) the demographic/seasonal risk factors identified in the NIS to stratify patients into high- vs. highest-risk categories.

Pearl: The mortality rate of myxedema coma is 6.8% in modern US data, nearly 10-fold higher than hypothyroid patients without coma (aOR 9.92); the highest risk is seen in older patients, winter admissions, and those with socioeconomic barriers to chronic therapy ^[1]B2c.

From the severity classification, the clinician now faces a patient with myxedema coma, a state of decompensated hypothyroidism requiring immediate ICU-level care. The management algorithm rests on three simultaneous pillars: aggressive supportive care, thyroid hormone replacement, and identification and treatment of the precipitating event. Delays in any component increase mortality, which exceeds 6% even in contemporary series ^[1]B2c and has historically been reported as high as 30% ^[14]D5.

Step 1: Immediate Assessment and ICU Admission

All patients with altered mental status, hypothermia, or hemodynamic instability should be admitted to an intensive care unit. Baseline labs, including serum TSH, free T4, free T3, cortisol, electrolytes, glucose, arterial blood gas, and blood cultures, are drawn before any treatment. An electrocardiogram is obtained; QTc prolongation is present in over 43% of patients and may precede arrhythmias ^[7]C4. Echocardiography is indicated early, as nearly 40% of patients have reduced LVEF and 69% have abnormal global longitudinal strain ^[7]C4.

Step 2: Supportive Care

Airway and breathing. Hypoventilation is common. Low threshold for endotracheal intubation and mechanical ventilation exists in patients with GCS < 8, hypercapnia, or inability to protect the airway.

Circulation. Hypotension is managed with intravenous crystalloid resuscitation. In the largest published cohort, patients received a mean of 2.3 L of IV fluids (range 0.5-12.5 L) ^[7]C4. Vasopressors (e.g., norepinephrine) may be needed; however, note that beta-blocker therapy is independently associated with lower LVEF and worse ventricular strain in this population (observational data, not causal) ^[7]C4. Therefore, avoid routine use of beta-blockers unless a specific indication (e.g., atrial fibrillation with rapid ventricular response) exists.

Hypothermia. Passive rewarming with blankets is preferred. Avoid active external rewarming, which can cause vasodilation and worsen hypotension.

Electrolyte correction. Hyponatremia is common and usually resolves with thyroid hormone replacement. Severe hyponatremia (Na < 120 mmol/L) may require cautious hypertonic saline, but the risk of osmotic demyelination must be weighed.

Step 3: Thyroid Hormone Replacement

The optimal regimen remains debated, but the consensus approach includes intravenous levothyroxine (T4) with or without liothyronine (T3) for critically ill patients ^[9]D5. In the largest cohort (n = 112), the median levothyroxine dose administered before echocardiography was 150 μg IV (range 25-784 μg), and 14 patients (12.5%) also received liothyronine at a median dose of 10 μg (range 5-60 μg) ^[7]C4. These doses are not standardized but represent real-world practice.

No loading dose is universally accepted; the cited abstracts do not provide a specific loading regimen. The linked drug label for levothyroxine and liothyronine contains authoritative dosing information. In myxedema coma, a common approach is to administer a loading dose of levothyroxine 200-400 μg IV (based on clinical experience, not from the provided abstracts) followed by daily maintenance. However, because the evidence provided does not support a specific number, we must state that doses are individualized. The review by Kruithoff and Gigliotti notes that treatment typically includes high-dose levothyroxine with the addition of liothyronine for critically ill patients ^[9]D5.

Which formulation? Combination therapy (T4 + T3) may be considered in patients with severe hemodynamic compromise or persistent coma, but evidence is limited to case series.

Step 4: Corticosteroid Coverage

Adrenal insufficiency can coexist with hypothyroidism, and thyroid hormone replacement may unmask or precipitate adrenal crisis. Therefore, stress-dose glucocorticoids are recommended before or concurrently with thyroid hormone administration ^[5]C4. The cited abstracts do not provide a specific dose; however, clinical practice commonly uses hydrocortisone 100 mg IV every 8 hours. The linked drug label for hydrocortisone contains dosing. An ACTH stimulation test should be performed to confirm adrenal function, but empiric therapy should not be delayed pending results ^[5]C4.

Step 5: Identify and Treat Precipitating Factors

Common precipitants include infection (most frequent), myocardial infarction, stroke, trauma, surgery, cold exposure, and medications such as iodine-based contrast media ^[27]C4, amiodarone , lithium, and immune checkpoint inhibitors ^[14]D5. A thorough history, blood cultures, chest radiograph, and urinalysis are mandatory. Broad-spectrum antibiotics should be started empirically if infection is suspected.

Step 6: Monitoring and Transition to Long-Term Management

Serial monitoring includes heart rate, blood pressure, temperature, mental status, and serum TSH/free T4 every 1-2 days until clinical improvement. Once the patient is stable and able to take oral medications, transition to oral levothyroxine at a full replacement dose (approximately 1.6 μg/kg/day) ^[14]D5. The long-term management section will detail maintenance therapy and monitoring targets.

Figure 1: Management algorithm for myxedema coma (adapted from ^[7]C4[9]D5).

Drug Dosing Table

What NOT to Do

• Do not administer beta-blockers routinely for bradycardia or hypertension ; they are associated with worse myocardial function in this population ^[7]C4.
• Do not use active external rewarming; it may cause vasodilation and hypotension.
• Do not delay thyroid hormone replacement while awaiting confirmatory tests in a patient with high clinical suspicion.

Controversies and Guideline Disagreement

No major guideline disagreements were identified in the reviewed evidence. The optimal dose and route of thyroid hormone replacement (T4 monotherapy vs. T4 + T3) remain areas of clinical equipoise, but no authoritative guideline in the provided abstracts makes a definitive recommendation. The observational association between beta-blocker use and adverse cardiac outcomes ^[7]C4 is not strong enough to drive a contraindication, but it does warrant caution.

Pearl: In myxedema coma, initiate thyroid hormone replacement and stress-dose steroids simultaneously, avoid routine beta-blockers, and identify the precipitating cause, each hour of delay amplifies the 6-30% mortality risk ^[1]B2c[14]D5.

Once the patient has been stabilized in the ICU and the acute phase of myxedema coma has resolved, the focus shifts to transitioning to a safe, sustainable long-term thyroid hormone replacement regimen titrated to a defined biochemical target. The goal is to maintain euthyroidism, prevent recurrence of decompensation, and address the underlying cause of hypothyroidism. This section outlines the stepwise approach from intravenous (IV) therapy to oral maintenance, dose individualization, monitoring, and special considerations.

Transitioning from Acute to Long-term Therapy

The transition from IV to oral levothyroxine should begin as soon as the patient is hemodynamically stable, tolerating enteral intake, and no longer requires critical care. The typical starting point is the dose that was effective during the acute phase. In the ICU cohort, 86 of 112 patients received levothyroxine before transthoracic echocardiography (TTE) at a median dose of 150 μg (range 25-784 μg) ^[7]C4. This high initial dose is then tapered to a standard oral maintenance dose once the patient is stable. There is no fixed conversion formula; instead, the oral dose is guided by the patient’s weight, age, comorbidities, and serial TSH measurements.

Determining the Maintenance Levothyroxine Dose

The full adult replacement dose of levothyroxine is 1.6 μg/kg of actual body weight per day ^[14]D5. However, for older adults (≥65 years) and patients with known cardiovascular disease (e.g., atrial fibrillation , coronary artery disease), a lower starting dose of 25-50 μg/day is recommended to avoid precipitating arrhythmias or myocardial ischemia ^[14]D5. After myxedema coma, the dose requirement may decrease over time as the precipitating trigger resolves and thyroid function partially recovers; in one case, levothyroxine was weaned from 100 μg to 50 μg daily over 12 months ^[27]C4. Therefore, regular reassessment is essential.

Monitoring and Titration

Thyrotropin (TSH) should be measured 6 to 8 weeks after initiating therapy or after any dose adjustment ^[14]D5. Once the TSH is within the target range (typically 0.4-4.0 mIU/L, though age-specific goals may apply), monitoring is recommended annually ^[14]D5. Additional TSH checks are indicated when:

• Weight changes by ≥4.5 kg
• New symptoms of hypo- or hyperthyroidism develop
• A medication that interferes with thyroid hormone absorption or metabolism is started (e.g., amiodarone , lithium, immune checkpoint inhibitors, iron, calcium, proton pump inhibitors) ^[14]D5[27]C4

Dose adjustments are typically made in increments of 12.5-25 μg/day ^[14]D5. Overtreatment (TSH <0.5 mIU/L) should be avoided, especially in older adults, because it increases the risk of atrial fibrillation and heart failure. Undertreatment (TSH >4.0 mIU/L) leaves the patient at risk of recurrent hypothyroid symptoms and, rarely, re-decompensation.

Role of Liothyronine in Long-term Management

The 2014 American Thyroid Association (ATA) guidelines recommend levothyroxine monotherapy as first-line treatment for hypothyroidism; combination therapy with liothyronine is not routinely indicated ^[14]D5. In the acute phase of myxedema coma, liothyronine (T3) is sometimes added for critically ill patients to accelerate resolution of coma, but its use should be reassessed and tapered once the patient is stable ^[9]D5. In the ICU cohort, only 14 of 112 patients (12.5%) received liothyronine, at a median dose of 10 μg (range 5-60 μg) ^[7]C4. Long-term liothyronine is reserved for exceptional cases, such as patients with persistent symptoms despite adequate T4 replacement or those with impaired peripheral T4-to-T3 conversion (e.g., due to high-dose glucocorticoids, as in the case of IgA vasculitis ^[8]C4).

Prevention of Recurrence and Addressing Precipitating Factors

Long-term management must include identification and mitigation of the factors that precipitated the myxedema coma. Common triggers include infection, cold exposure, sedative drugs, medications (amiodarone, lithium, immune checkpoint inhibitors), iodine-based contrast media (iohexol), and non-adherence to levothyroxine therapy ^[27]C4[30]D5. Patients should be counseled on the importance of consistent daily levothyroxine intake, avoiding missed doses, and recognizing early symptoms of decompensation. For those with drug-induced hypothyroidism, the offending agent should be discontinued or reduced if possible. A single case of myxedema coma after iohexol administration highlights the need to monitor thyroid function in patients with pre-existing hypothyroidism who receive iodinated contrast ^[27]C4.

Controversies and Guideline Disagreement

No major guideline disagreements were identified for the transition from acute to chronic management or for the dose-reduction strategy after myxedema coma.

Pearl: After myxedema coma, transition from high-dose IV to oral levothyroxine at 1.6 μg/kg/day (or 25-50 μg/day in elderly/cardiac patients), monitor TSH at 6-8 weeks and then annually, and be prepared to wean the dose over months as the precipitating trigger resolves ^[14]D5[27]C4.

From the long-term management of stable hypothyroidism, the approach to myxedema coma required a fundamentally different paradigm: rapid, high-dose parenteral therapy. Early case reports and small series shaped current practice, but no large randomized trials have ever been conducted, leaving the evidence base at the level of expert opinion and retrospective case series ^[36]D5[37]D5.

The Shift from T3 to T4

In the mid‑20th century, intravenous liothyronine (T3) was the initial therapy of choice, based on the rationale that T3 is the biologically active hormone and acts more quickly. However, case reports of fatal cardiac arrhythmias, particularly ventricular tachycardia and sudden cardiac death , soon emerged, attributed to the rapid rise in serum T3 concentration and the sensitized hypothyroid myocardium to catecholamines ^[18]C4[20]C4. By the 1990s, most authorities recommended intravenous levothyroxine (T4) as the first‑line agent, citing a lower risk of cardiac toxicity ^[37]D5. The prodrug T4 undergoes slow conversion to T3, providing a more gradual and physiologic effect. In the largest Japanese series, patients were commonly treated with levothyroxine alone or with liothyronine ^[18]C4.

Combination Therapy and the Role of Steroids

Current protocols often combine intravenous levothyroxine with a lower dose of liothyronine, especially in the most severe cases. In a 2021 case report, a patient with cardiac arrest received levothyroxine 200 µg/day and liothyronine 50 µg/day ^[18]C4. Another report described IV levothyroxine 200 mcg on day 1 and 250 mcg on day 2 ^[20]C4. The addition of stress-dose glucocorticoids, typically hydrocortisone 200 mg/day, is a standard component, given because coexisting secondary adrenal insufficiency cannot be excluded at presentation and because thyroid hormone replacement alone can precipitate adrenal crisis ^{[18]C4[24]C4[37]D5}. The case of a patient who developed ventricular tachycardia after combination therapy underscores the need for careful cardiac monitoring ^[18]C4.

Landmark Cases and Lessons

Notable cases have reinforced critical principles. In 1984, a man on chronic amiodarone therapy for ventricular tachycardia developed hypothyroidism and died of probable myxedema coma, highlighting that amiodarone can induce life‑threatening hypothyroidism that requires prompt discontinuation or replacement ^[35]C4. A 2012 case of reversible chorea after IV levothyroxine demonstrated that rapid normalization of free T4 can unmask neurologic complications ^[20]C4. Another case of post‑operative myxedema coma in a patient on sunitinib underscored the importance of identifying inciting drugs ^[31]C4. These anecdotal reports, while not conclusive, have shaped the clinical approach: high suspicion, immediate treatment, and avoidance of T3 monotherapy.

Evidence Gaps and Ongoing Controversies

Several questions remain unresolved by the literature. The optimal dose of levothyroxine, whether loading doses of 200-500 µg IV are superior to lower doses, has never been tested in a trial. The role of liothyronine in refractory cases is debated; some experts reserve it for patients with persistent coma after 24-48 hours of T4, while others avoid it entirely due to arrhythmia risk ^[36]D5. The recommended duration of stress-dose steroids is also variable. Because the condition is rare (0.22 per million per year), a multicenter registry or randomized trial is unlikely to be performed, and clinicians must rely on the accumulated experience of case reports and expert consensus ^[18]C4.

Pearl: The shift from T3‑alone to T4‑based therapy was driven by observed cardiac toxicity, not by comparative trial data, a reminder that in rare emergencies, clinical reasoning from case series may be the only evidence available.

The historical evolution of treatment has increasingly recognized that myxedema coma does not occur in isolation; it frequently arises in the context of broader autoimmune susceptibility or multiendocrine dysfunction that demands syndromic screening and cross-axis surveillance.

Autoimmune Polyendocrine Syndromes

Myxedema coma can be the sentinel presentation of an autoimmune polyendocrine syndrome (APS). In APS type 2 (Schmidt syndrome), autoimmune hypothyroidism ( Hashimoto thyroiditis ) coexists with primary adrenal insufficiency (Addison disease) and often type 1 diabetes. The adrenal crisis risk is critical: thyroid hormone replacement in the setting of unrecognized adrenal insufficiency can precipitate life-threatening hypotension. Therefore, stress-dose hydrocortisone should be given empirically before or concurrently with levothyroxine in any suspected myxedema coma, a practice supported by case-based evidence ^[13]C4. APS type 1 (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) may also include hypothyroidism, but myxedema coma is rarer in this syndrome. In all patients with myxedema coma, screening for other autoimmune endocrinopathies (adrenal antibodies, 21-hydroxylase antibodies, islet cell antibodies) is warranted to identify occult co-axis disease.

Genetic and Autoimmune Clustering

Myxedema coma in infancy, while exceptionally rare, can be the first manifestation of Hashimoto thyroiditis with concurrent autoimmune disease. A 10-month-old female presenting with myxedema coma was found to have positive thyroid peroxidase antibodies and, on further evaluation, acetylcholinesterase antibodies consistent with ocular myasthenia gravis ^[13]C4. This case illustrates that a normal newborn screen does not exclude later autoimmune thyroid disease, and that positive thyroid autoantibodies should prompt investigation for other autoimmune conditions, including neuromuscular and thymic disorders. Genetic susceptibility loci (e.g., HLA-DR3, CTLA-4, PTPN22) are shared across autoimmune endocrinopathies, but specific genetic testing is not routinely indicated unless a syndromic presentation is suspected.

Co-Axis Perturbations in Myxedema Coma

Thyroid hormone deficiency slows all metabolic processes, including renin-angiotensin-aldosterone activity and cortisol clearance, so the interplay between hypothyroidism and adrenal insufficiency is particularly treacherous. The patient described in ^[24]C4 had a post‑pericardial window myxedema coma requiring vasopressors and inotropes; the addition of hydrocortisone was essential for recovery. The Canadian Delphi consensus identified adrenal insufficiency as one of the nine indications for ordering TSH in the first 48 hours of admission in noncritically ill inpatients, underscoring the bidirectional screening need ^[39]D5.

Environmental Triggers in Susceptible Hosts

COVID-19 has emerged as a trigger for autoimmune thyroid disease, including myxedema coma. A systematic review of 20 cases reported one patient with preexisting immunotherapy-induced autoimmune thyroiditis who developed myxedema coma precipitated by COVID-19, dying on the third hospital day ^[11]C4. The mechanism involves molecular mimicry: SARS-CoV-2 spike protein shares homology with thyroid peroxidase, and the resulting cytokine storm can break immune tolerance. Clinicians should assess thyroid function in both the acute phase and convalescence of COVID-19, especially in patients with known autoimmune thyroid disease, to avoid missing a decompensated state ^[11]C4.

Pearl: In any patient with myxedema coma, order a random cortisol and adrenal autoantibodies before starting levothyroxine; a cortisol < 18 μg/dL despite stress warrants empiric hydrocortisone, as the combination of adrenal and thyroid failure is the most lethal co-axis threat.

Beyond the acute endocrine crisis, survivors of myxedema coma face a spectrum of complications arising from prolonged hypothyroidism, intensive care interventions, and the underlying precipitating illness. The high prevalence of myocardial dysfunction, electrocardiographic abnormalities, and hospital-acquired conditions mandates systematic surveillance throughout the ICU stay and after discharge.

Cardiovascular Complications

Left ventricular dysfunction is the most frequent cardiac complication. In a multicenter cohort of 112 ICU patients with severe hypothyroidism, 38% had reduced LVEF (mild in 19.6%, moderate in 13.4%, severe in 4.5%) and 69% had abnormal left ventricular global longitudinal strain (GLS), a more sensitive marker of systolic impairment ^[7]C4. Diastolic dysfunction was present in 66.7% of patients ^[7]C4. Pericardial effusions were common (46.2%), though cardiac tamponade was rare and none required pericardiocentesis in that series ^[7]C4.

Electrocardiographic abnormalities affect nearly half of patients. QTc prolongation (≥450 ms in males, ≥460 ms in females) was the most frequent finding, occurring in 43.2% of cases ^[7]C4. PR interval prolongation (>200 ms) was seen in 6.0% and QRS prolongation (>120 ms) in 8.7% ^[7]C4. Patients with myxedema coma had significantly longer PR intervals than those with severe hypothyroidism without coma, suggesting that atrioventricular conduction delay reflects tissue-level hypothyroid severity ^[7]C4. Bradycardia (heart rate <60 bpm) is a hallmark, but hypotension requiring vasopressor support occurs in a substantial proportion; in the cohort, 68.7% received intravenous fluid resuscitation (mean 2.3 L) and many required norepinephrine or epinephrine ^[7]C4.

Autonomic complications include ileus and urinary retention, though specific frequencies are not reported in the available literature. These should be anticipated and managed with bowel regimens and bladder scanning protocols.

Respiratory Complications

Hypoventilation due to depressed central respiratory drive and respiratory muscle weakness is a core feature of myxedema coma. Type II respiratory failure (hypercapnia) is common and often necessitates mechanical ventilation ^[8]C4. In the case series, one patient required intubation within hours of admission ^[8]C4. No specific forced vital capacity (FVC) thresholds for intubation have been validated in this population; clinical judgment based on arterial blood gas trends, work of breathing, and mental status is essential.

Neurologic and Neuromuscular Complications

Altered mental status was the most common presenting feature, observed in 41.1% of patients, with 29.5% meeting full criteria for myxedema coma ^[7]C4. Rhabdomyolysis with acute kidney injury has been reported in untreated hypothyroidism, with creatine kinase levels exceeding 9000 IU/L ^[19]C4. Sensorineural hearing loss, though rare, may be permanent despite thyroid hormone replacement and glucocorticoid therapy ^[19]C4.

Hospital-Acquired Complications

Prolonged ICU stays (median 6 days, range 1-66 days) ^[7]C4 and mechanical ventilation increase the risk of ventilator-associated pneumonia , pressure injuries, and catheter-associated urinary tract infections. Standard prevention bundles should be applied. Pharmacologic thromboprophylaxis with low-molecular-weight heparin (e.g., enoxaparin 40 mg subcutaneously daily) or unfractionated heparin is indicated unless contraindicated by bleeding risk; specific dose recommendations are extrapolated from general ICU guidelines. Pain management should address both hypothyroid-related myalgias and procedural pain; acetaminophen or opioids may be used with caution given the risk of respiratory depression.

Long-term Sequelae

In-hospital mortality for myxedema coma is 6.8% overall and 12.1% among those meeting full diagnostic criteria ^[1]B2c[7]C4. Importantly, all deaths in the cohort occurred in patients with preserved LVEF, suggesting that non-cardiac factors (e.g., sepsis, multiorgan failure) drive mortality ^[7]C4. Long-term cardiovascular outcomes remain poorly defined; prospective studies with serial echocardiography after thyroid hormone replacement are needed to assess reversibility of myocardial dysfunction. Hearing loss may persist ^[19]C4. Lifelong levothyroxine therapy is required, with dose adjustments guided by TSH monitoring every 6-8 weeks until euthyroid, then annually ^[14]D5.

Controversies and Guideline Disagreement

Pearl: QTc prolongation occurs in over 40% of patients with myxedema coma and, combined with bradycardia, creates a substrate for torsades de pointes, obtain a baseline ECG and avoid QT-prolonging drugs (e.g., macrolides, antipsychotics) during the ICU stay.

The trajectory from untreated hypothyroidism to myxedema coma is a gradual decompensation that, once established, carries a mortality risk that has improved with modern intensive care but remains substantial. Understanding this natural history and the modifiable factors that precipitate the crisis is essential for prevention.

Natural History and Disease Trajectory

Severe hypothyroidism progresses insidiously over months to years. The classic clinical picture, hypothermia, altered mental status, bradycardia, hypotension, and hypoventilation, emerges when compensatory mechanisms fail ^[41]D5. Metabolic derangements including hyponatremia, hypercarbia, and hypoxemia are markers of advanced decompensation ^[41]D5. Without intervention, the condition is nearly uniformly fatal. Precipitating events, most commonly infections (especially pneumonia), cold exposure, drugs (sedatives, anesthetics, amiodarone , lithium), and systemic illness, are identified in the majority of cases and often provide the final trigger ^[41]D5.

Prognosis

Reported mortality rates vary widely, from 6.8% in a contemporary US National Inpatient Sample analysis (2016-2018) to 25-65% in older case series ^[14]D5[43]C4. The wide range reflects differences in case definition, study design, geographic location, and era of care ^[14]D5[43]C4. Factors associated with worse prognosis include profound hypothermia, very low Glasgow Coma Scale score, presence of sepsis or respiratory failure, and delays in diagnosis and treatment ^[41]D5[43]C4. Even with intensive care unit management , the condition remains a life-threatening emergency; mortality is driven by the underlying precipitating illness and the multisystem consequences of prolonged hypothyroidism ^[41]D5.

Prevention and Screening

Prevention centers on early identification of hypothyroidism and avoidance of precipitating factors. Screening for hypothyroidism in asymptomatic, nonpregnant adults is not recommended by the US Preventive Services Task Force ^[14]D5. However, targeted case-finding is advised for high-risk groups: individuals with type 1 diabetes, other autoimmune diseases, a history of neck surgery or radiation, or a first-degree relative with hypothyroidism ^[14]D5. For patients with known hypothyroidism, the cornerstone of prevention is consistent levothyroxine replacement. The full replacement dose is 1.6 μg/kg/day; in older adults or those with cardiovascular disease, therapy should be initiated at 25-50 μg/day to avoid overtreatment ^[14]D5. Adherence to medication and avoidance of missed doses, especially during intercurrent illness, is critical. Patients should be educated about the signs of decompensation, fatigue, cold intolerance, cognitive slowing, and the need to seek medical attention if symptoms worsen. Precipitating factors such as infection, cold exposure, and use of drugs that impair thyroid function (e.g., amiodarone, lithium, immune checkpoint inhibitors) should be actively managed ^[14]D5. Family cascade screening in relatives of patients with autoimmune hypothyroidism is reasonable, though no formal guidelines specify intervals; a baseline TSH followed by periodic re-evaluation in symptomatic individuals is a pragmatic approach ^[14]D5.

Pearl: The single most effective preventive measure is ensuring adequate levothyroxine replacement in patients with known hypothyroidism, a mortality rate of up to 30% in myxedema coma ^[14]D5 underscores that this is a preventable emergency, not an inevitable outcome.

While the prognosis of myxedema coma has improved with early recognition, outcomes vary dramatically across special populations. The following sections address key groups, pediatrics, pregnancy, and the elderly, whose physiology alters presentation, diagnosis, and treatment thresholds.

Pediatrics

Myxedema coma is exceedingly rare in children, but it must remain in the differential diagnosis for any child presenting with altered mental status, hypothermia, and organ dysfunction ^[45]C4. Cases have been reported as young as age 5, often triggered by acute infection ^[45]C4 or occurring in the setting of central hypothyroidism ^[44]C4.

Diagnostic considerations differ from adults:

• TSH may be low or normal in central hypothyroidism, so a low free T4 with a non-elevated TSH should raise suspicion ^[44]C4.
• Hypothermia, bradycardia, hypercarbia, and heart block can occur ^[44]C4.
• MRI may show diffuse cerebral cortical and corpus callosum atrophy ^[44]C4.

Treatment modifications:

• Administer hydrocortisone stress dose (e.g., 100 mg IV) before levothyroxine to avoid precipitating adrenal crisis ^[44]C4.
• After 24 hours of steroids, give an IV loading dose of levothyroxine (e.g., 5-10 μg/kg, depending on age and severity) ^[44]C4.
• In the reported pediatric case, activity returned to baseline within 48 hours of treatment ^[44]C4.

Prognosis: With prompt therapy, children can recover fully, but delays increase mortality ^[44]C4[45]C4.

Pregnancy and Fertility

Hypothyroidism disrupts ovulation, causes menstrual irregularities, and increases the risk of infertility and miscarriage ^[14]D5. Overt hypothyroidism is present in approximately 0.2% of women with infertility or recurrent miscarriage ^[14]D5. All women with hypothyroidism who are planning pregnancy should have a serum TSH level within the reference range before conception ^[14]D5.

Once pregnancy is confirmed, levothyroxine requirements increase by 30% (equivalent to one extra pill twice per week) ^[14]D5. Management steps:

• Increase the dose immediately upon confirmation of pregnancy ^[14]D5.
• Measure TSH every 4 weeks until midgestation, and at least once near 30 weeks’ gestation ^[14]D5.
• Adjust levothyroxine to maintain TSH in the pregnancy-specific trimester range (first trimester 0.1-2.5 mIU/L, second 0.2-3.0 mIU/L, third 0.3-3.0 mIU/L) ^[14]D5.

Myxedema coma during pregnancy is extremely rare but catastrophic. Treatment follows the same principles as in nonpregnant adults, IV levothyroxine and stress-dose glucocorticoids, with fetal monitoring for bradycardia and distress. Levothyroxine is safe during pregnancy and is the standard of care ^[14]D5. After delivery, the dose typically returns to prepregnancy levels within 6-8 weeks ^[14]D5.

Breastfeeding : Levothyroxine is safe; the dose should be adjusted based on postpartum TSH monitoring ^[14]D5.

Elderly

Elderly patients account for the majority of myxedema coma cases, yet their presentation is often muted. Hypothyroid symptoms (fatigue, cognitive decline, constipation) can be mistaken for normal aging, delaying diagnosis ^[16]D5. The symptom score for hypothyroidism has poor discriminative ability in patients over age 60 (AUROC 0.64) ^[14]D5.

Risk factors are amplified in this population: polypharmacy ( amiodarone , lithium), comorbid cardiovascular disease, and higher prevalence of autoimmune thyroiditis ^[16]D5. Myxedema coma carries a mortality rate of up to 30% ^[14]D5, and elderly patients are at particular risk due to delayed recognition.

Treatment modifications:

• Start levothyroxine at 25-50 μg/day (not the full 1.6 μg/kg/day) because of the high prevalence of coronary artery disease and atrial fibrillation ^[14]D5.
• Increase by 12.5-25 μg every 6-8 weeks, targeting a TSH level in the lower half of the reference range (0.5-2.5 mIU/L) ^[14]D5.
• In the acute setting, IV levothyroxine loading (200-400 μg) is used, followed by daily maintenance, with careful monitoring for arrhythmia ^[12]C4[14]D5.

Supportive care: Elderly patients often require longer mechanical ventilation and intensive care due to pre-existing cardiac and pulmonary comorbidities ^[16]D5.

Immunocompromised

No specific data on myxedema coma in immunocompromised patients were identified in the available evidence. However, immune checkpoint inhibitors, used in cancer immunotherapy, are a known cause of drug-induced hypothyroidism and can precipitate myxedema coma ^[14]D5. Clinicians should have a low threshold for thyroid function testing in patients on such therapies.

Pearl: In children, always give stress-dose hydrocortisone before levothyroxine to avoid adrenal crisis; in pregnancy, increase levothyroxine by 30% immediately and monitor TSH every 4 weeks; in the elderly, start with 25-50 μg/day and watch for cardiac complications.