Myxoedema coma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Myxoedema coma is the extreme end of hypothyroid decompensation, usually in longstanding untreated or inadequately treated disease exposed to a stressor. Reduced thermogenesis and metabolic drive cause hypothermia and bradycardia; impaired ventilatory response causes hypercapnia; altered water handling produces hyponatraemia; and reduced cardiac output can lead to shock and organ dysfunction.

Diagnosis is clinical and should remain on the differential even when temperature is not profoundly low or the patient still speaks. TSH is usually very high in primary disease, but may be normal or low in central hypothyroidism; biochemical magnitude alone neither proves nor excludes the emergency. Non-thyroidal illness can also distort values, so physiology and history lead.

Management is simultaneous resuscitation, hormone and steroid treatment, cautious correction of metabolic derangement, and active search for the trigger. Evidence for exact thyroid-hormone regimens is limited, formulations and local protocols vary, and cardiac disease changes risk. The bedside clinician should therefore involve specialists early and verify the current BNF and institutional policy rather than copying a static dose.

Key points

The syndrome is severe physiological decompensation from hypothyroidism and does not require literal coma; altered cognition may range from slowing and delirium to unresponsiveness.
Think of the cluster: hypothermia, bradycardia, hypotension, hypoventilation or hypercapnia, hyponatraemia, hypoglycaemia, oedematous appearance and reduced consciousness.
Infection, cold exposure, myocardial infarction, stroke, sedatives or opioids, surgery and interruption of levothyroxine are important precipitants.
Obtain thyroid tests and cortisol promptly, but treatment must not be delayed for confirmatory results when the clinical syndrome is convincing.
Give parenteral hydrocortisone before thyroid hormone until clinically important adrenal insufficiency is excluded, because replacement can precipitate cortisol collapse.
After parenteral hydrocortisone, the current levothyroxine injection SmPC recommends an adult intravenous loading dose of 200–500 micrograms, never above 500 micrograms, followed by 1.2 micrograms/kg daily, usually 75–90 micrograms; use the lower end or a modified plan when cardiac risk is high.
Provide ventilatory support early when respiratory drive is inadequate; normal oxygen saturation does not exclude dangerous carbon-dioxide retention.
Warm passively and gradually, correct sodium and glucose cautiously, treat infection empirically when suspected, and avoid rapid shifts that add neurological or circulatory injury.
Continuous cardiac, temperature, fluid and biochemical monitoring is essential because arrhythmia, ischaemia and treatment-related instability can emerge during recovery.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Longstanding severe hypothyroidism

Untreated, undertreated or poorly absorbed thyroid hormone deficiency reduces metabolic and organ reserve until a further stress causes decompensation.

Acute precipitating illness

Infection, cold exposure, surgery, trauma, cardiovascular events or sedating medicines can overwhelm already limited thermoregulatory, respiratory and circulatory capacity.

Central hypothyroidism

Pituitary or hypothalamic disease can cause the same emergency with a non-raised TSH and possible accompanying cortisol deficiency.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Metabolic drive becomes critically low
Severe thyroid hormone deficiency reduces thermogenesis, heart rate, cardiac output and ventilatory responsiveness as the process continues.
2
Water and gas handling deteriorate
Impaired free-water excretion promotes hyponatraemia, while reduced ventilatory drive raises carbon dioxide; both changes worsen cerebral dysfunction and depressed consciousness.
3
A precipitant overwhelms reserve
Infection, cold or medicine effects increase demand or suppress function, tipping compensated hypothyroidism into organ failure.
4
Multisystem decompensation develops
Hypothermia, bradycardia, hypotension, hypoglycaemia and altered consciousness reinforce one another and reduce thyroid-hormone delivery and metabolism.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Neurological deteriorationRed flag

Lethargy, slowed responses, confusion, psychosis, seizures, stupor or coma may occur. A fall in consciousness alongside hypothermia or bradycardia is particularly concerning and mandates airway assessment.

Respiratory failureRed flag

Slow shallow breathing, upper-airway oedema, obesity, effusions or reduced respiratory drive can produce hypoxia and hypercapnia. Obtain a blood gas and involve anaesthesia early when ventilation is failing.

Cardiovascular compromiseRed flag

Bradycardia, low cardiac output, hypotension, conduction delay, pericardial effusion and occasionally heart failure or ischaemia create a fragile circulation that can be worsened by aggressive warming or hormone loading.

Metabolic signatureRed flag

Hyponatraemia, hypoglycaemia, raised creatine kinase, renal impairment and respiratory acidosis support severe systemic disease but are not specific; correction speed and underlying mechanism must be assessed.

Hypothyroid phenotype

Dry coarse skin, non-pitting oedema, sparse hair, hoarse voice, macroglossia, delayed reflexes, constipation or ileus and a thyroidectomy scar can provide retrospective clues when history is limited.

Hidden precipitantRed flag

Pneumonia or urinary infection may lack fever in a hypothermic patient; review myocardial ischaemia, stroke, trauma, drug exposure and omitted hormone even if one trigger initially seems obvious.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Bedside ABCDE observations and core temperatureFirst step
Why
Identify immediate ventilatory, circulatory and thermoregulatory failure.
Interpretation and limitations
Low temperature, bradycardia, hypotension and falling consciousness increase clinical probability; trends after support matter more than a single severity score.
02
TSH, free T4 and free T3
Why
Document thyroid status and help distinguish primary from central disease.
Interpretation and limitations
Low free T4 supports deficiency; TSH is often high in primary disease but can be low or normal centrally. Do not grade emergency severity from hormone concentrations alone.
03
Serum cortisol before steroid if feasible
Why
Preserve diagnostic information about coincident adrenal insufficiency.
Interpretation and limitations
Draw immediately only when it causes no delay, then give hydrocortisone. Critical-illness cortisol needs endocrine interpretation and should not postpone resuscitation.
04
Blood gas with glucose and lactate
Why
Detect hypoventilation, acid-base disturbance, hypoglycaemia and tissue hypoperfusion.
Interpretation and limitations
Hypercapnic respiratory acidosis signals ventilatory failure and can require intubation; recurrent low glucose suggests limited reserve or associated adrenal dysfunction.
05
Urea, electrolytes, osmolality and urine studies
Why
Characterise hyponatraemia and guide a safe correction strategy.
Interpretation and limitations
Hypotonic hyponatraemia is common, but volume status, cortisol deficiency and medicines alter management. Set a documented correction ceiling with critical care.
06
ECG, troponin and echocardiography when indicated
Why
Assess bradyarrhythmia, ischaemia, pump function and pericardial effusion.
Interpretation and limitations
Low voltage, conduction slowing or effusion may accompany hypothyroidism; dynamic ischaemia or tamponade physiology requires its own urgent pathway.
07
Sepsis and precipitant screen
Why
Find the stressor that converted compensated disease into collapse.
Interpretation and limitations
Obtain cultures and targeted chest or other imaging without delaying antimicrobials when infection is likely; also investigate infarction, stroke and medicine toxicity.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Sepsis

Hypothermia, hypotension and confusion can reflect infection, which may also precipitate myxoedema coma and therefore requires parallel treatment.

Sedative or opioid toxicity

Reduced consciousness, bradypnoea and hypothermia may follow overdose; exposure history and toxicological response help distinguish or identify coexistence.

Adrenal crisis

Hypotension, hyponatraemia and hypoglycaemia overlap strongly, and central pituitary disease may cause both deficiencies together when supported by the history and examination.

Non-thyroidal illness

Critical illness can distort TSH and free hormones without primary thyroid failure, so clinical history and the whole biochemical pattern remain essential.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First hourResuscitate and recruit specialistsFirst stepSevere hypothyroid decompensation is clinically suspected.

1Call critical care, endocrinology and senior acute support; perform ABCDE with continuous ECG, core temperature, glucose and urine-output monitoring.
2Secure oxygenation and ventilation, obtain blood gas and prepare intubation when consciousness or carbon-dioxide clearance is inadequate.
3Take thyroid tests, cortisol, cultures and metabolic bloods rapidly, but begin steroid, supportive and infection treatment without waiting for results.

02Hormone sequenceSteroid before thyroid replacementThe syndrome is convincing and adrenal insufficiency has not been safely excluded.

1Give stress-dose parenteral hydrocortisone immediately after a cortisol sample when obtainable without delay, following the current endocrine emergency protocol.
2After steroid protection, agree intravenous levothyroxine with endocrinology and critical care. The current injection SmPC recommends 200–500 micrograms as the adult loading dose, never above 500 micrograms, followed by 1.2 micrograms/kg daily, usually 75–90 micrograms; reduce intensity for advanced age, low body mass, coronary disease or arrhythmia.
3Reserve liothyronine for selected specialist-led circumstances because rapid action may help severe disease but carries substantial cardiac and dosing risk.

03SupportCorrect physiology without overshootHypothermia, hypotension, hyponatraemia, hypoglycaemia or organ failure accompanies the presentation.

1Use passive insulation and controlled environmental warming; avoid vigorous peripheral heat that can cause vasodilation and circulatory collapse.
2Treat low glucose immediately, give cautious isotonic fluid guided by volume and cardiac status, and correct sodium within a documented safe limit.
3Use vasopressor, ventilatory and renal support through critical care when response is inadequate, while reassessing hormone, cortisol and trigger treatment.

04PrecipitantTreat the event that caused collapseInfection, vascular disease, medicine exposure or omitted replacement is possible.

1Give local-guideline antimicrobials promptly after appropriate cultures when sepsis is suspected, remembering that fever and leukocytosis may be absent.
2Evaluate ECG and neurological findings for infarction or stroke, and reverse or withhold sedatives, opioids and other contributing medicines where safe.
3Once stabilised, establish why hypothyroidism developed or treatment failed and create a discharge plan that prevents missed replacement and recurrence.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Prevents or treats cortisol failure while adrenal insufficiency remains possible during thyroid replacement.

Hydrocortisone emergency cover

Common UK emergency practice begins with 100 mg intravenously or intramuscularly, followed by the current adrenal-crisis schedule; verify ongoing dose and route with the BNF and local protocol.

Draw cortisol first only if immediate treatment is not delayed. Monitor glucose, sodium, potassium, fluid balance and infection, then reassess need with endocrinology after recovery.

Replaces deficient T4 and restores metabolic function alongside resuscitation and precipitant treatment.

Levothyroxine in myxoedema coma

After glucocorticoid protection, give an adult intravenous loading dose of 200–500 micrograms, never exceeding 500 micrograms, then parenteral levothyroxine 1.2 micrograms/kg daily, usually 75–90 micrograms, with a lower-end or modified specialist plan for major cardiac risk.

Parenteral therapy and large loading doses can provoke ischaemia or arrhythmia. Give only after steroid protection, verify formulation, and follow serial clinical and biochemical response.

Provides faster active hormone effect when specialists judge potential benefit to exceed cardiac risk.

Liothyronine in selected severe presentations

Intravenous dosing is individualised by endocrinology and intensive care using the current BNF monograph; do not extrapolate a routine ward regimen from oral hypothyroidism treatment.

Evidence is limited and excess can cause myocardial ischaemia or tachyarrhythmia. Avoid unsupervised use, especially with coronary disease, and monitor continuously in critical care.

Treats a frequent precipitant that may present without fever in profound hypothyroidism.

Empirical antimicrobial therapy when infection suspected

Choose agents, dose, route and review time from the current local severe-infection guideline after cultures when feasible, with renal adjustment and allergy assessment.

Do not delay for normal temperature or white count. Review microbiology, source control, renal function, interactions and de-escalation every day.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Respiratory failure

Reduced ventilatory drive, respiratory-muscle weakness and sedative sensitivity cause carbon-dioxide retention and may require critical-care support.

Cardiovascular collapse

Bradycardia, low cardiac output and impaired vascular responses can produce refractory hypotension, arrhythmia and progressive organ hypoperfusion.

Neurological injury

Hyponatraemia, hypoglycaemia, hypercapnia, hypothermia and poor cerebral perfusion combine to deepen progressive delirium, seizure and coma.

Adrenal decompensation

Starting thyroid hormone without cortisol protection in unrecognised central adrenal insufficiency can increase demand and precipitate crisis.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use continuous ECG, blood pressure, oxygenation and core-temperature monitoring in a critical-care environment, documenting rhythm or ischaemic change during hormone replacement.
Repeat blood gases according to ventilatory instability and after intervention; a rising carbon-dioxide level can precede obvious oxygen desaturation.
Measure glucose frequently until stable and follow sodium with a predefined correction target to avoid osmotic neurological injury.
Record fluid input, urine output, weight and bedside congestion because both low-output physiology and over-resuscitation are dangerous.
Trend free T4 and TSH at specialist-selected intervals, interpreting TSH lag and any liothyronine exposure rather than chasing rapid normalisation.
Reassess cultures, imaging and cardiovascular or neurological triggers daily; recovery of temperature alone does not prove the precipitant is controlled.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Coma is not compulsory

The historic name can delay recognition. A hypothermic, bradycardic patient with cognitive slowing and hypercapnia may already have the emergency before unresponsiveness develops.

TSH cannot grade collapse

Clinical severity reflects chronicity, reserve and precipitating stress. Central disease may have no TSH rise, while a very high value can occur in a stable outpatient.

Warm the core cautiously

Aggressive external heat can dilate a constricted peripheral circulation and worsen hypotension; insulation plus controlled critical-care support is safer than rapid surface warming.

Look beyond oxygen saturation

Reduced ventilatory drive can generate severe hypercapnia despite supplemental oxygen and an apparently acceptable saturation, making blood-gas assessment and clinical work of breathing essential.

Infection may look cold

Profound hypothyroidism blunts fever and inflammatory responses. Cultures and empirical treatment should follow overall sepsis probability, not reassurance from a low temperature.

11Common pitfallsFrequent interpretation and management errors.

01
Rejecting the diagnosis because the patient is drowsy rather than comatose.
02
Waiting for TSH confirmation before beginning resuscitation and steroid protection.
03
Giving thyroid hormone before addressing possible adrenal insufficiency.
04
Using vigorous heating that causes peripheral vasodilation and haemodynamic deterioration.
05
Correcting chronic hyponatraemia rapidly without a documented ceiling and frequent checks.
06
Assuming a normal temperature or white count excludes infection.
07
Copying a fixed liothyronine or loading regimen without current BNF, formulation and specialist verification.