Myxoedema Coma

Quick Answer

One-liner: Myxoedema coma is a life-threatening endocrine emergency of severe hypothyroidism characterised by hypothermia, altered mental status, and multi-organ dysfunction, requiring immediate IV levothyroxine, hydrocortisone, and ICU admission.

Myxoedema coma represents the most severe manifestation of decompensated hypothyroidism with mortality rates of 25-60% even with optimal treatment [1,2]. It typically affects elderly females (4:1 ratio) during winter months and is almost always precipitated by an acute stressor such as infection, cold exposure, or medication non-compliance. The classic triad of hypothermia, altered consciousness, and a precipitating event should trigger immediate empiric treatment before laboratory confirmation.

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Thyroid gland anatomy, hypothalamic-pituitary-thyroid axis
• Physiology: Thyroid hormone synthesis, T4 to T3 conversion, thermogenesis, metabolic regulation
• Pharmacology: Levothyroxine, liothyronine, hydrocortisone pharmacokinetics and interactions

Fellowship Exam Relevance

• Written: Clinical recognition, diagnostic criteria, medication dosing, precipitant identification
• OSCE: Resuscitation scenarios, communication with family regarding poor prognosis, ICU handover
• Key domains tested: Medical Expert, Collaborator, Communicator

High-Yield ACEM Topics

1. Empiric treatment BEFORE laboratory confirmation
2. Hydrocortisone BEFORE or WITH thyroid hormone replacement
3. Passive rewarming ONLY (active rewarming causes arrhythmias)
4. Precipitant identification (infection, medications, cold exposure)
5. ICU admission for all cases

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Key Points

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Epidemiology

Australian/NZ Specific

• Higher rates in elderly populations in cooler southern regions (Victoria, Tasmania, South Island NZ)
• Remote and rural patients at risk due to medication non-compliance and delayed presentation
• Indigenous populations may have delayed access to endocrine services [6,7]

Risk Factors

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Pathophysiology

Mechanism

Myxoedema coma results from the profound deficiency of thyroid hormones (T3 and T4), causing a critical slowing of all metabolic processes. The brain, heart, lungs, and kidneys all depend on thyroid hormone for normal function.

Severe T3/T4 deficiency
       |
       v
+------+------+------+------+
|      |      |      |      |
v      v      v      v      v
CNS    CVS    Resp   Renal  Temp
|      |      |      |      |
v      v      v      v      v
Coma   Brady  CO2    SIADH  Hypo-
       card   reten  hypo   thermia
       ia     tion   Na

Pathological Progression by System

Cardiovascular [10,11]

• Decreased beta-adrenergic receptor expression leads to bradycardia
• Decreased cardiac contractility reduces cardiac output by 30-50%
• Pericardial effusion (up to 30% of patients) causes low voltage ECG
• QT prolongation from delayed repolarisation predisposes to Torsades de Pointes

Thermoregulation [12]

• Reduced basal metabolic rate decreases heat production
• Impaired UCP1 (uncoupling protein) in brown adipose tissue
• Decreased alpha-adrenergic responsiveness impairs vasoconstriction
• Result: Profound hypothermia often below 35 degrees C, frequently below 32 degrees C

Neurological [13]

• Cerebral hypometabolism causes decreased level of consciousness
• Hyponatraemia contributes to cerebral oedema
• Hypoxia and hypercapnia from hypoventilation worsen encephalopathy
• GCS typically 3-10 at presentation

Respiratory [14,15]

• Blunted hypoxic and hypercapnic ventilatory drives
• Respiratory muscle weakness (diaphragm, intercostals)
• Macroglossia and laryngeal oedema cause upper airway obstruction
• 80% of patients require mechanical ventilation

Renal/Electrolyte [16,17]

• Non-osmotic ADH release (SIADH-like state)
• Decreased GFR from reduced cardiac output
• Result: Dilutional hyponatraemia (often below 130 mmol/L, sometimes below 120 mmol/L)

Metabolic [18,19]

• Decreased gluconeogenesis and glycogenolysis cause hypoglycaemia
• Reduced insulin clearance prolongs insulin effect
• Concurrent adrenal insufficiency in 5-10% (Schmidt syndrome)

Why It Matters Clinically

The multi-organ dysfunction explains the high mortality and the need for:

1. ICU-level monitoring for cardiac arrhythmias
2. Mechanical ventilation for respiratory failure
3. Passive rewarming to prevent cardiovascular collapse
4. Hydrocortisone for potential adrenal insufficiency

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Clinical Approach

Recognition

Classic Triad

1. Altered mental status (confusion to coma)
2. Hypothermia (temperature often below 35 degrees C)
3. Precipitating event (infection, cold, medication)

Initial Assessment

Primary Survey

• A: Macroglossia, laryngeal oedema - anticipate difficult airway
• B: Hypoventilation, decreased respiratory effort, SpO2 often below 90%
• C: Bradycardia (often 40-60 bpm), hypotension, cool peripheries
• D: GCS often 3-10, pupils sluggish, hyporeflexia with delayed relaxation
• E: Hypothermia (below 35 degrees C), non-pitting oedema (myxoedema), dry skin

History

Key Questions

Collateral History Critical

• Often patients cannot provide history due to altered consciousness
• Contact family, GP, pharmacy for medication history
• Check electronic medical records for previous thyroid results

Examination

General Inspection

• Appearance: Puffy face, periorbital oedema, coarse features
• Skin: Dry, cool, yellowish (carotenaemia), non-pitting oedema
• Hair: Coarse, brittle, loss of outer third of eyebrows
• Behaviour: Bradyphrenic, slow to respond, obtunded

Specific Findings

Myxoedema Coma Scoring System (Popoveniuc) [20]

Score Interpretation:

• greater than 60: High likelihood of myxoedema coma - treat empirically
• 25-59: Possible myxoedema coma - consider treatment
• below 25: Unlikely myxoedema coma

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Investigations

Immediate (Resus Bay)

Standard ED Workup

Infection Screen (Precipitant Identification)

Advanced/Specialist

Point-of-Care Ultrasound

• Cardiac: Pericardial effusion (common), assess contractility
• IVC: Volume status assessment (may show collapsed IVC if hypovolaemic)
• Lung: Pleural effusions, B-lines (pulmonary oedema)

ECG Findings in Myxoedema Coma [21,22,23]

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Management

Immediate Management (First 10 minutes)

1. Activate resuscitation team - this is an endocrine emergency
2. High-flow oxygen if hypoxic (SpO2 below 90%) - prepare for intubation
3. IV access x2 large bore cannulae
4. Core temperature measurement (rectal/oesophageal)
5. BSL - treat hypoglycaemia with 50 mL 50% dextrose IV
6. ECG - look for bradycardia, QT prolongation
7. Bloods: TSH, fT4, cortisol, UEC, FBC, CK, VBG
8. DO NOT WAIT for results - treat empirically if clinical suspicion high

Resuscitation

Airway

• Anticipate difficult airway: Macroglossia, laryngeal oedema, obesity
• Early intubation if GCS below 8, hypercapnia (PaCO2 greater than 60), severe hypoxia
• Use smaller ETT (6.5-7.0) due to laryngeal oedema
• Video laryngoscopy preferred
• Have surgical airway equipment immediately available

Breathing

• Mechanical ventilation required in 80% of cases
• Target: SpO2 92-96%, PaCO2 normalisation over 24-48 hours
• Avoid hyperventilation - gradual correction of chronic hypercapnia
• Lung protective ventilation: Vt 6-8 mL/kg IBW

Circulation

• Hypotension management:
  • Cautious IV fluids (crystalloid boluses 250 mL) - risk of fluid overload
  • Vasopressors if MAP below 65 mmHg despite fluids (noradrenaline first line)
  • Treat underlying cause (sepsis, haemorrhage)
• Bradycardia:
  • Often unresponsive to atropine
  • Will improve with thyroid hormone replacement
  • Temporary pacing rarely required

Medications

CRITICAL: Steroid First Rule

T4 vs T3 Therapy Debate [27,28]

Current consensus: Start with IV T4 loading; add low-dose T3 if minimal improvement after 24-48 hours or if severely obtunded [1,2].

Paediatric Dosing (Rare - Congenital/Juvenile Myxoedema)

Temperature Management

Hyponatraemia Management [16,17]

Correction rate: Maximum 8-10 mmol/L in first 24 hours to avoid osmotic demyelination syndrome

Precipitant Treatment

Definitive Care

• ICU admission mandatory for all cases
• Endocrinology consultation within first 6 hours
• Multi-organ support as needed
• Daily TFTs to monitor response
• Transition to oral when clinically improved and tolerating oral intake

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Disposition

ICU Admission Criteria (Mandatory for Myxoedema Coma)

All patients with suspected myxoedema coma require ICU/HDU admission for:

• Continuous cardiac monitoring (arrhythmia risk)
• Invasive blood pressure monitoring
• Mechanical ventilation if required
• Hourly neurological observations
• Core temperature monitoring
• IV thyroid hormone and steroid administration

Predictors of Poor Outcome [3,31,32]

Discharge Criteria

• Myxoedema coma patients are never discharged from ED
• After ICU/ward recovery:
  • Stable on oral levothyroxine
  • Normal mental status
  • Normal temperature maintained
  • Precipitant treated
  • Endocrinology follow-up arranged
  • GP notified with medication plan

Follow-up Requirements

• Endocrinology: 2-4 weeks post-discharge
• GP: 1 week post-discharge for TFT check
• Allied health: Social work if compliance issues, OT for home assessment
• Education: Sick-day rules, medication importance, when to seek help

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Special Populations

Elderly Considerations [33]

• Higher mortality in patients greater than 70 years
• Lower loading dose of T4 (200 mcg) to reduce cardiac risk
• Higher prevalence of CAD - monitor for ischaemia with hormone replacement
• Polypharmacy common - review for precipitating medications
• Frailty assessment important for goals of care discussions
• Higher rates of atypical presentation - may not mount fever with infection

Pregnancy

• Extremely rare - myxoedema coma with pregnancy survival is unusual
• Foetal compromise expected if maternal condition severe
• Urgent obstetric and endocrine consultation
• Standard T4 replacement with close monitoring
• Consider delivery if viable gestation and maternal condition deteriorating

Patients with Known Cardiac Disease

• Use lower T4 loading dose (200 mcg or even 100 mcg)
• Avoid T3 or use very low doses (5 mcg)
• Continuous cardiac monitoring essential
• Serial troponins to detect ischaemia
• Cardiology consultation if CAD history

Post-Thyroidectomy/RAI Patients

• No endogenous thyroid reserve - entirely dependent on exogenous hormone
• Non-compliance is common precipitant
• May have concurrent hypoparathyroidism (hypocalcaemia)
• Check calcium levels

Drug-Induced Hypothyroidism [8,9]

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Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Maori Considerations:

Access Barriers

• Remote communities: Delayed presentation is common due to geographic isolation
• Medication access: Levothyroxine supply chains may be disrupted in remote areas
• Specialist services: Limited endocrinology access outside major centres [6,7]
• Refrigeration: T3 requires refrigeration - cold chain maintenance challenging in remote areas

Cultural Safety

• Involve Aboriginal Health Workers/Maori Health Workers in care planning
• Family/whanau-centred care: Include family in discussions about prognosis and treatment
• Communication: Use interpreters if language barriers exist
• Discharge planning: Ensure community health service follow-up is arranged

Specific Health Disparities

• Higher rates of chronic disease comorbidities (diabetes, cardiovascular disease)
• Potential delays in diagnosis of underlying hypothyroidism
• Medication adherence challenges related to social determinants of health
• Higher rates of Graves' disease requiring thyroidectomy in Indigenous Australians [7]

Maori Health Considerations (NZ)

• Whanau involvement: Extended family should be involved in care decisions
• Tikanga: Respect cultural protocols around illness and end-of-life care
• Manaakitanga: Hospitality and care for the whole person
• Karakia: Spiritual practices may be important to patient and family
• Maori Health Navigator services: Involve early if available

Remote/Rural Communication

• Use telehealth for endocrinology consultation
• Provide clear written discharge instructions
• Coordinate with Aboriginal Medical Services/Maori Health Providers
• Ensure medication supply chain for ongoing levothyroxine

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Remote/Rural Considerations

Pre-Hospital/Retrieval

RFDS Considerations

• Early notification: Contact RFDS/retrieval services as soon as myxoedema coma suspected
• Time-critical transfer: These patients deteriorate rapidly - do not delay transfer for "complete workup"
• Pre-departure treatment: Start hydrocortisone and T4 BEFORE retrieval if available

Information for Retrieval Team

• Core temperature (actual reading, not "low")
• Current GCS and trend
• Airway status - intubated or not, any concerns
• Current medications given (hydrocortisone, T4, dose, time)
• IV access and fluid status
• Precipitant identified or suspected
• TFT results if available

Resource-Limited Setting

Modified Approach When Resources Limited

Minimum Requirements for Rural Hospital Management

• IV hydrocortisone (usually available in all hospitals)
• IV or oral levothyroxine
• Continuous cardiac monitoring
• Ability to intubate and ventilate
• Temperature monitoring
• BSL monitoring and dextrose
• Retrieval service access

Telemedicine Consultation

When to call for advice:

• Any suspected myxoedema coma
• Uncertainty about diagnosis
• Medication dosing questions
• Retrieval decision-making
• Goals of care discussions in elderly/frail patients

Services:

• NSW: ICNSW Adult Retrieval (1300 799 127)
• VIC: Adult Retrieval Victoria (1300 363 855)
• QLD: QEMS Retrieval (1300 799 127)
• SA: SA Ambulance Special Operations (08 8274 0440)
• WA: RFDS Western Operations
• NT: RFDS Central Operations, CareFlight
• NZ: Regional Critical Care units

Transfer Considerations

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Pitfalls and Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Myxoedema Coma Resuscitation

Format: Resuscitation Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are the senior registrar in a regional ED. An 80-year-old woman has been brought in by ambulance after being found unresponsive at home. Initial observations show: GCS 6, HR 38, BP 75/40, RR 8, SpO2 82% on 15L O2, Temperature 31.5 degrees C. She has a thyroidectomy scar noted on her neck. Lead this resuscitation.

Examiner Instructions:

• The patient has myxoedema coma precipitated by a UTI
• TFTs: TSH greater than 100, fT4 below 3
• BSL 2.1 mmol/L
• Sodium 118 mmol/L
• Urine shows pyuria and bacteria
• ECG shows sinus bradycardia with low voltage and QT prolongation
• Allow the candidate to intubate (difficult but successful)
• Provide results when requested

Actor/Patient Brief: Mannequin-based scenario. If family member required, daughter is anxious and wants to know "what is wrong with my mum."

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Steroid before T4, passive rewarming stated, precipitant identified

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Station 2: Breaking Bad News - Poor Prognosis

Format: Communication Time: 11 minutes Setting: Relatives room adjacent to ED

Candidate Instructions:

You are the senior registrar in a metropolitan ED. Mrs Margaret Thompson, 78, was admitted 6 hours ago with myxoedema coma. Despite treatment with hydrocortisone and levothyroxine, she remains deeply comatose (GCS 4), is mechanically ventilated, and on vasopressor support. Her 24-hour CT brain shows diffuse cerebral oedema. The ICU consultant has reviewed and believes her prognosis is very poor. You need to speak to her daughter, Sarah, about her mother's condition and prognosis.

Examiner Instructions:

• Daughter has been waiting anxiously
• She does not know how serious the condition is
• She becomes distressed when hearing poor prognosis
• She asks "should we turn off the machines?"
• Assess candidate's ability to deliver bad news compassionately and answer questions appropriately

Actor/Patient Brief (Daughter): You are Sarah, 52. Your mother has been fit and well until recently. You noticed she was "a bit slow" over the past few weeks but didn't think much of it. You feel guilty for not checking on her sooner. When told the prognosis is poor, you become tearful and ask what you should do. You want to know if your mother is suffering.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Honest prognosis, empathetic response to distress, does not give false hope

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Station 3: Clinical Examination - Hypothyroidism

Format: Examination Time: 11 minutes Setting: Clinical examination area

Candidate Instructions:

This 65-year-old woman has been feeling tired and cold. Please examine her thyroid and any relevant systems, present your findings, and state your differential diagnosis.

Examiner Instructions:

• Patient has overt hypothyroidism (not coma, but demonstrating signs)
• Signs to be present: Thyroidectomy scar OR goitre, dry skin, coarse features, periorbital oedema, bradycardia, delayed relaxation of reflexes, hoarse voice
• No reduced consciousness (this is an examination station)
• Ask for differential and investigations at end

Actor/Patient Brief: You are tired all the time, feel cold when others are warm, have gained weight, and your voice has become deeper. You may have had thyroid surgery years ago (show scar) OR have a visible goitre.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Delayed relaxation of reflexes, systematic thyroid examination

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SAQ Practice

Question 1 (6 marks)

Stem: A 75-year-old woman is found unresponsive at home in winter. On arrival to ED she has: GCS 7, HR 40, BP 80/50, T 32.5 degrees C, SpO2 85% on room air.

Question: List THREE clinical features that would support a diagnosis of myxoedema coma (2 marks) and outline FOUR key steps in the immediate management (4 marks).

Model Answer:

Clinical features supporting myxoedema coma (2 marks - any 3):

• Hypothermia (below 35 degrees C) (0.5 mark)
• Bradycardia unresponsive to atropine (0.5 mark)
• Altered consciousness/coma (0.5 mark)
• Hypotension (0.5 mark)
• Evidence of previous thyroid surgery (scar) (0.5 mark)
• Myxoedema features (periorbital oedema, dry skin, macroglossia) (0.5 mark)
• Non-pitting oedema (0.5 mark)

Immediate management (4 marks - 1 mark each):

1. Airway protection - intubate if GCS below 8 or respiratory failure (1 mark)
2. Passive rewarming with blankets ONLY - no active rewarming (1 mark)
3. Hydrocortisone 100 mg IV BEFORE thyroid hormone (1 mark)
4. Levothyroxine 200-400 mcg IV loading dose (1 mark)

Examiner Notes:

• Accept: IV dextrose for hypoglycaemia, IV fluids cautiously, oxygen therapy
• Do not accept: Active rewarming, giving T4 before steroids stated, generic "resuscitation"

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Question 2 (8 marks)

Stem: A 68-year-old man on amiodarone for atrial fibrillation presents with confusion and lethargy. His TFTs show TSH 75 mU/L and fT4 4 pmol/L.

Question: a) Explain the mechanism by which amiodarone causes hypothyroidism (2 marks) b) List FOUR other medications that can cause hypothyroidism (2 marks) c) Outline the management priorities for this patient if he develops myxoedema coma (4 marks)

Model Answer:

a) Mechanism of amiodarone-induced hypothyroidism (2 marks):

• Amiodarone contains 37% iodine by weight (0.5 mark)
• Massive iodine load causes Wolff-Chaikoff effect - acute inhibition of thyroid hormone synthesis (1 mark)
• Patients with underlying thyroid disease (Hashimoto's) or in iodine-sufficient areas fail to "escape" from this inhibition (0.5 mark)

b) Other medications causing hypothyroidism (2 marks - 0.5 each):

• Lithium
• Tyrosine kinase inhibitors (sunitinib, sorafenib)
• Checkpoint inhibitors (pembrolizumab, nivolumab)
• Interferon-alpha
• Thalidomide/lenalidomide
• Bexarotene
• High-dose iodinated contrast

c) Management priorities (4 marks - 1 mark each):

1. Cease amiodarone (though effect persists due to long half-life) (1 mark)
2. Hydrocortisone 100 mg IV before thyroid hormone replacement (1 mark)
3. IV levothyroxine loading dose 200-400 mcg (1 mark)
4. ICU admission for monitoring and supportive care (1 mark)

• Accept: Passive rewarming, treat precipitants, cardiology consultation for alternative antiarrhythmics

Examiner Notes:

• Accept any valid drug causing hypothyroidism with reference
• Emphasise amiodarone cessation and the delay before effects resolve

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Question 3 (6 marks)

Stem: You are working in a remote ED and suspect a 70-year-old woman has myxoedema coma. You do not have access to IV levothyroxine.

Question: a) Outline how you would manage this patient's thyroid hormone replacement with available resources (3 marks) b) List THREE key pieces of information you would provide to the retrieval team (3 marks)

Model Answer:

a) Modified thyroid hormone replacement (3 marks):

• Oral levothyroxine can be given via nasogastric tube if IV unavailable (1 mark)
• Dose: 100-200 mcg orally/NG as loading (lower than IV due to incomplete absorption) (1 mark)
• Give hydrocortisone 100 mg IV first (usually available in all hospitals) (0.5 mark)
• Arrange urgent retrieval for IV therapy and ICU care (0.5 mark)

b) Information for retrieval team (3 marks - 1 mark each):

1. Core temperature (actual reading) and trend
2. GCS and neurological status
3. Medications given (hydrocortisone dose, T4 dose and route, timing)
4. Airway status - intubated or concerns about airway
5. Current haemodynamics and vasopressor requirements if any
6. Suspected precipitant (infection, medication, cold exposure)
7. TFT results if available

Examiner Notes:

• Accept any reasonable adaptation for resource-limited setting
• Emphasise retrieval coordination is a priority

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Question 4 (8 marks)

Stem: An 80-year-old Aboriginal woman from a remote community in the Northern Territory is being retrieved to your hospital with suspected myxoedema coma. She has a GCS of 8, is hypothermic, and has not been taking her thyroid medication for "several months."

Question: a) List FOUR barriers to care that may have contributed to her presentation (2 marks) b) Describe FOUR culturally appropriate considerations for her care (4 marks) c) Outline TWO discharge planning priorities to prevent recurrence (2 marks)

Model Answer:

a) Barriers to care (2 marks - 0.5 each):

• Geographic isolation/remoteness from healthcare services
• Medication supply chain difficulties in remote areas
• Limited access to endocrinology specialists
• Financial barriers to medication
• Competing health and social priorities
• Limited health literacy regarding medication importance
• Previous negative healthcare experiences
• Language barriers

b) Culturally appropriate considerations (4 marks - 1 mark each):

1. Involve Aboriginal Health Workers/Indigenous Liaison Officers in care planning (1 mark)
2. Family-centred care - include family in discussions and decision-making (1 mark)
3. Use interpreters if there is any language barrier (1 mark)
4. Respect cultural practices and beliefs around illness (1 mark)

• Accept: Acknowledge Sorry Business if relevant, offer to connect with traditional healers, ensure cultural safety, avoid paternalistic communication

c) Discharge planning priorities (2 marks - 1 mark each):

1. Coordinate with remote area health service/Aboriginal Medical Service for ongoing medication supply and monitoring (1 mark)
2. Establish clear follow-up plan with endocrinology via telehealth and community health worker support (1 mark)

• Accept: Medication pre-packing (Webster packs), GP letter with clear plan, community health worker involvement, patient and family education about importance of medication

Examiner Notes:

• Emphasise cultural safety and avoiding judgment about medication compliance
• Acknowledge social determinants of health

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Differential Diagnosis

Conditions Mimicking Myxoedema Coma

Key Differentiating Features of Myxoedema Coma

1. Hypothermia + Bradycardia + Altered consciousness - classic triad
2. Physical features - myxoedema facies, delayed reflexes, thyroidectomy scar
3. History - known hypothyroidism, medication non-compliance
4. Laboratory - markedly elevated TSH (in primary hypothyroidism), very low fT4

Concurrent Conditions to Consider

• Adrenal insufficiency (5-10% of cases) - treat empirically with hydrocortisone
• Sepsis (most common precipitant) - treat empirically with antibiotics
• Myocardial infarction - may be precipitant or consequence
• Pericardial effusion - common, rarely causes tamponade

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Complications

Immediate Complications

Treatment-Related Complications

Long-Term Complications (Survivors)

• Cognitive impairment - may persist despite treatment
• Recurrence - if medication compliance not addressed
• Cardiovascular disease - pre-existing, may worsen
• Depression - common in hypothyroidism

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Monitoring and Response to Treatment

Monitoring Parameters

Expected Response Timeline

Failure to Respond

If no improvement after 48-72 hours:

1. Reassess precipitant - is infection adequately treated? Hidden source?
2. Consider adding T3 if on T4 monotherapy (impaired conversion)
3. Reassess adrenal status - is cortisol adequate?
4. Review complications - cardiac event, stroke, overwhelming sepsis?
5. Goals of care discussion - early involvement of palliative care if futility

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Prognosis and Outcomes

Mortality Data

Prognostic Factors [31,32,33]

Survival Predictors

Factors associated with survival:

• Age below 60 years
• Early recognition and treatment
• Mild hypothermia (greater than 34 degrees C)
• Identifiable and treatable precipitant
• Prompt thyroid hormone and steroid administration
• Response to treatment within 72 hours

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Case-Based Learning

Case 1: Classic Presentation

Presentation: 75-year-old woman found unresponsive at home in July (winter). Lives alone. Neighbours noticed she hadn't collected her mail for 3 days.

Initial Assessment:

• GCS 5 (E1V2M2)
• HR 38, BP 75/40
• RR 8, SpO2 78% on room air
• Temperature 30.2 degrees C (rectal)
• Thyroidectomy scar noted

Investigation Results:

• BSL 2.3 mmol/L
• TSH greater than 100 mU/L, fT4 below 3 pmol/L
• Na 116 mmol/L, K 4.2 mmol/L
• Cortisol 120 nmol/L
• ABG: pH 7.18, pCO2 78, pO2 52, HCO3 18

Management:

1. Intubated for airway protection and respiratory failure
2. 50 mL 50% dextrose for hypoglycaemia
3. Hydrocortisone 100 mg IV
4. Levothyroxine 200 mcg IV (reduced dose due to age)
5. Passive rewarming with blankets
6. Cautious IV fluids, noradrenaline infusion for MAP below 65
7. ICU admission

Outcome: Slow improvement over 5 days. Extubated day 7. Discharged day 14 on oral levothyroxine with GP follow-up.

Learning Points:

• Always check for thyroidectomy scar
• Treat hypoglycaemia immediately
• Lower T4 dose in elderly
• Recovery takes days to weeks

Case 2: Atypical - "Normal" TSH

Presentation: 62-year-old man with known pituitary macroadenoma (treated with surgery 3 years ago) presents with 2 weeks progressive confusion. Has been "feeling off" for months.

Initial Assessment:

• GCS 10 (E3V3M4)
• HR 52, BP 105/70
• Temperature 35.2 degrees C
• No thyroidectomy scar
• Pale, dry skin, mild periorbital oedema

Investigation Results:

• TSH 1.8 mU/L (normal range 0.4-4.0)
• fT4 4 pmol/L (very low)
• Cortisol 85 nmol/L (very low)

Interpretation: Central hypothyroidism (pituitary failure). TSH is inappropriately "normal" for the very low fT4. Also has secondary adrenal insufficiency.

Management:

1. Hydrocortisone 100 mg IV (critical - has AI)
2. Levothyroxine 300 mcg IV loading
3. ICU admission for monitoring
4. Endocrinology consultation

Learning Points:

• Normal TSH does NOT exclude hypothyroidism if pituitary disease present
• Always check fT4 as the diagnostic test
• Pituitary patients often have multiple hormone deficiencies

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Patient Education Materials

For Patients Recovering from Myxoedema Coma

Why This Happened: Your body needs thyroid hormone to work properly. When thyroid hormone levels become very low, your body slows down to the point where vital organs (brain, heart, lungs) cannot function normally. This is called myxoedema coma.

What You Need to Do:

1. Take your thyroid medication EVERY DAY - never miss a dose
2. Get regular blood tests to check your thyroid hormone levels
3. See your doctor regularly for thyroid monitoring
4. Carry a medical alert indicating you need thyroid hormone

Warning Signs to Watch For:

• Feeling extremely tired or sleepy
• Feeling very cold when others are warm
• Confusion or difficulty thinking
• Slow heartbeat
• Constipation

If you notice these symptoms, seek medical help immediately.

For Family Members

Your family member has a condition that requires lifelong thyroid hormone replacement. They must take their medication every day without fail. If they become confused, very sleepy, or cold, this may indicate their thyroid hormone levels are low - this is a medical emergency. Call 000 immediately.

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Australian Guidelines

ARC/ANZCOR

ARC/ANZCOR

• ANZCOR Guideline 11.10.1: General management of acutely ill patients - principles apply to myxoedema coma resuscitation
• Key differences from AHA/ERC: ANZCOR uses 2 initial breaths, ARC-specific drug dosing recommendations

Therapeutic Guidelines

• Therapeutic Guidelines - Endocrinology: Recommends levothyroxine 200-400 mcg IV loading, hydrocortisone 100 mg IV q8h
• Australian Medicines Handbook: T4 and hydrocortisone dosing consistent with international guidelines

State-Specific

• NSW eTG: Follows ATA guidelines for myxoedema coma management
• VIC ClinGuide: Endocrine emergencies protocols available

International Guidelines Referenced

• American Thyroid Association (ATA) 2014: Guidelines for treatment of hypothyroidism [26]
• European Thyroid Association: Consensus on thyroid emergencies

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References

Guidelines

1. Australian Resuscitation Council. ANZCOR Guideline 11.10.1: Adult Resuscitation. 2024. Available from: https://resus.org.au
2. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751. PMID: 25232844

Key Evidence - Epidemiology and Outcomes

3. Wiersinga WM. Myxedema and Coma (Severe Hypothyroidism). Endotext [Internet]. 2018. PMID: 30390918
4. Ono Y, Ono S, Yasunaga H, et al. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan. J Epidemiol. 2017;27(3):117-122. PMID: 27568853
5. Dutta P, Bhansali A, Masoodi SR, et al. Predictors of outcome in myxoedema coma: a study from a tertiary care centre. Crit Care. 2008;12(1):R1. PMID: 21671911
6. Rodriguez I, Fluiters E, Perez-Mendez LF, et al. Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol. 2004;180(2):347-350. PMID: 14765987

Indigenous Health

7. Zhu L, Atkins CL, Hamid A, et al. Graves' disease in Indigenous Australians: a case-control study. Intern Med J. 2019;49(12):1500-1504. PMID: 31055581
8. Zhao Y, Guthridge S, Magnus A, et al. Burden of disease and injury in Aboriginal and non-Aboriginal populations in the Northern Territory. Med J Aust. 2004;180(10):498-502. PMID: 15139825
9. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander Health Performance Framework. 2023.

Pathophysiology

10. Wall CR. Cardiovascular manifestations of hypothyroidism. Postgrad Med. 2014;126(7):117-125. PMID: 25313465
11. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116(15):1725-1735. PMID: 17923583
12. Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011;2011:493462. PMID: 21447472
13. Kwaku MP, Burman KD. Myxedema coma. J Intensive Care Med. 2007;22(4):224-231. PMID: 17712051

Respiratory Complications

14. Ladenson PW. Myxedema coma. Thyroid Today. 1998;21(1):1-6.
15. Zwillich CW, Pierson DJ, Hofeldt FD, et al. Ventilatory control in myxedema and hypothyroidism. N Engl J Med. 1975;292(13):662-665. PMID: 1113761

Hyponatraemia and Metabolic

16. Wiersinga WM, Chopra IJ. Thyroid hormone binding and metabolism. In: De Groot LJ, et al, eds. Endocrinology. 7th ed. 2015.
17. Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol. 2010;205(1):1-13. PMID: 20016054
18. Chidakel A, Mentuccia D, Ladenson PW. Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid. 2005;15(8):899-903. PMID: 16131332
19. Chung HR. Screening and management of thyroid dysfunction in preterm infants. Ann Pediatr Endocrinol Metab. 2019;24(1):15-21. PMID: 30943677

Diagnostic Criteria

20. Popoveniuc G, Chandra T, Sud A, et al. A diagnostic scoring system for myxedema coma. Endocr Pract. 2014;20(8):808-817. PMID: 24518183

ECG and Cardiac Manifestations

21. Schenck JB, Rizvi AA, Lin T. Severe primary hypothyroidism manifesting with torsades de pointes. Am J Med Sci. 2006;331(3):154-156. PMID: 16538078
22. Delhoume B, Dumont P, Music J. Cardiac complications of hypothyroidism. Presse Med. 2018;47(11-12 Pt 1):880-886. PMID: 30322682
23. Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2004;59:31-50. PMID: 14749496

Treatment

24. Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012;96(2):385-403. PMID: 22443982
25. Hylander B, Rosenqvist U. Treatment of myxoedema coma - factors associated with fatal outcome. Acta Endocrinol (Copenh). 1985;108(1):65-71. PMID: 3969817
26. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999;9(12):1167-1174. PMID: 10646654

T4/T3 Therapy

27. Ono Y, Ono S, Yasunaga H, et al. Factors associated with mortality of thyroid storm: analysis using a national inpatient database in Japan. Medicine (Baltimore). 2016;95(7):e2848. PMID: 26886631
28. Beynon J, Akhtar S, Kearney T. Predictors of outcome in myxoedema coma. Crit Care. 2008;12(1):111. PMID: 18310434

Rewarming

29. Jordan RM. Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am. 1995;79(1):185-194. PMID: 7808091
30. Reinhardt W, Mann K. Incidence, clinical picture and treatment of hypothyroid coma: results of a survey. Med Klin (Munich). 1997;92(9):521-524. PMID: 9411163

Drug-Induced Hypothyroidism

31. Bartalena L, Bogazzi F, Chiovato L, et al. 2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction. Eur Thyroid J. 2018;7(2):55-66. PMID: 30141270
32. Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23(6):723-733. PMID: 19942149

Prognosis

33. Ono Y, Ono S, Yasunaga H, et al. Thyroid storm in Japan: analysis using a national inpatient database. Crit Care. 2016;20:106. PMID: 27151042
34. Fliers E, Bianco AC, Langouche L, Boelen A. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol. 2015;3(10):816-825. PMID: 26071885
35. Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am. 2006;35(4):687-698. PMID: 17127141

Remote/Rural Medicine

36. Wakerman J, Humphreys JS. Remote health. In: Oxford Textbook of Rural Health. 2024.
37. Royal Flying Doctor Service of Australia. Annual Report. 2023.
38. Australian College of Rural and Remote Medicine. Telehealth in Remote Practice. 2024.

Additional Evidence

39. Savage MW, Mah PM, Weetman AP, Newell-Price J. Endocrine emergencies. Postgrad Med J. 2004;80(947):506-515. PMID: 15356350
40. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550-1562. PMID: 28336049
41. Pearce SH, Brabant G, Duntas LH, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2(4):215-228. PMID: 24783053
42. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism. Thyroid. 2016;26(10):1343-1421. PMID: 27521067