Thyroid Storm

Quick Answer

One-liner: Thyroid storm is a life-threatening hypermetabolic crisis requiring immediate multi-modal therapy to block thyroid hormone synthesis, release, and peripheral action.

Thyroid storm (thyrotoxic crisis) is an acute, severe, life-threatening exacerbation of thyrotoxicosis with multiorgan dysfunction involving cardiovascular (tachycardia, atrial fibrillation, heart failure), neurological (agitation, delirium, coma), gastrointestinal (diarrhoea, vomiting, hepatic dysfunction), and thermoregulatory systems (hyperpyrexia greater than 38.5°C). Mortality is 10-30% despite treatment. Immediate management requires a five-step approach: thionamides (propylthiouracil 500-1000 mg loading or carbimazole 40-60 mg), iodine 1 hour after thionamides (Lugol's iodine 5-10 drops TDS), beta-blockade (propranolol 40-80 mg PO q4h or 1-2 mg IV), corticosteroids (hydrocortisone 100 mg IV q8h), and supportive care (cooling, IV fluids, ICU admission).

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Thyroid gland anatomy, thyroid-pituitary axis
• Physiology: Thyroid hormone synthesis (iodination, coupling), T4/T3 conversion, peripheral effects (β-adrenergic, cardiac, metabolic)
• Pharmacology: Thionamides (propylthiouracil, carbimazole/methimazole), beta-blockers, iodine, corticosteroids

Fellowship Exam Relevance

• Written: Burch-Wartofsky Point Scale (BWPS), five-step management, differential diagnosis of hypermetabolic crisis
• OSCE: Resuscitation station (thyroid storm management), communication station (ICU admission discussion), multi-organ support
• Key domains tested: Medical Expert (multi-modal therapy sequencing), Communicator (family discussion), Leader (ICU coordination), Professional (recognition of precipitants)

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Key Points

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Epidemiology

Australian/NZ Specific

• Graves' disease prevalence in Australia: ~0.5%, with higher rates in coastal iodine-replete areas [9]
• AIHW data: Hyperthyroidism hospitalisations ~3,500/year nationally, with 1-2% developing thyroid storm [10]
• Māori and Pacific Islander populations have lower rates of autoimmune thyroid disease compared to European ancestry [11]
• Remote/rural areas face diagnostic delays due to limited access to endocrinology and thyroid imaging [12]

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Pathophysiology

Mechanism

Thyroid storm represents a decompensated state of severe thyrotoxicosis with excessive thyroid hormone action on peripheral tissues. The exact trigger for transition from uncomplicated thyrotoxicosis to storm remains incompletely understood but involves:

1. Overwhelming thyroid hormone levels - Elevated free T3 and T4 saturate negative feedback mechanisms
2. Precipitating physiological stress - Infection, surgery, trauma, or other illness increases metabolic demand
3. Loss of compensatory mechanisms - Downregulation of β-adrenergic receptors fails, cardiac reserve depletes, hepatic clearance diminishes
4. Enhanced cellular sensitivity - Tissues become hyperresponsive to catecholamines and thyroid hormones [13,14]

Pathological Progression

Precipitant (infection, surgery, RAI, non-compliance)
    ↓
Excessive thyroid hormone release + heightened adrenergic tone
    ↓
Hypermetabolic crisis (fever greater than 38.5°C, tachycardia greater than 140 bpm, agitation)
    ↓
Cardiovascular decompensation (AF, heart failure, hypotension)
    ↓
Multi-organ dysfunction (CNS, hepatic, cardiac, GI)
    ↓
Death (if untreated)

Why It Matters Clinically

• Cardiac effects: T3 increases β-adrenergic receptor density, cardiac output, and oxygen consumption → high-output heart failure, arrhythmias [15]
• Metabolic effects: Increased basal metabolic rate → hyperthermia, diaphoresis, catabolic state, muscle wasting [16]
• CNS effects: Direct T3 effects + catecholamine excess → agitation, psychosis, seizures, coma [17]
• GI/hepatic: Increased gut motility, hepatic congestion from heart failure → diarrhoea, hepatic dysfunction, jaundice [18]

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Clinical Approach

Recognition

Suspect thyroid storm in any patient with:

• Severe hyperthermia (greater than 38.5°C) + tachycardia disproportionate to fever
• New-onset atrial fibrillation or other tachyarrhythmia in a young patient
• Unexplained agitation, delirium, or altered mental status
• Known hyperthyroidism with recent illness, surgery, or medication non-compliance
• Classic physical signs: goitre, exophthalmos, tremor, warm moist skin [19]

Initial Assessment

Primary Survey (ABCDE)

• A (Airway): Usually patent unless severely altered conscious state (GCS below 8); anticipate need for intubation if coma or seizures
• B (Breathing): Tachypnoea (respiratory rate greater than 25), hyperventilation (respiratory alkalosis compensating for metabolic acidosis); assess for pulmonary oedema
• C (Circulation): Tachycardia (greater than 140 bpm), wide pulse pressure, bounding pulses, atrial fibrillation (10-35%); hypotension suggests cardiac decompensation; peripheral vasodilation despite high cardiac output
• D (Disability): Agitation, confusion, delirium, psychosis, seizures, coma (grave prognostic sign); Glasgow Coma Scale (GCS) score correlates with mortality
• E (Exposure): Hyperthermia (often greater than 39°C), profuse diaphoresis, warm peripheries; palpate for goitre, assess for exophthalmos, lid lag, pretibial myxoedema

Burch-Wartofsky Point Scale (BWPS) [20]

Interpretation:

• ≥45: Highly suggestive of thyroid storm
• 25-44: Impending thyroid storm
• below 25: Unlikely to be thyroid storm

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Appears unwell, distressed, agitated, diaphoretic
• Tachypnoeic, tachycardic, hyperpyrexic
• Warm, flushed, moist skin
• Thin, cachectic (chronic thyrotoxicosis)

Specific Findings

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Investigations

Immediate (Resus Bay)

Standard ED Workup

Advanced/Specialist

Point-of-Care Ultrasound (POCUS)

• Cardiac POCUS: Hyperdynamic LV, normal/reduced LVEF (if heart failure), valvular regurgitation, pericardial effusion (rare)
• Lung POCUS: B-lines (pulmonary oedema), pleural effusion
• IVC POCUS: Dilated, plethoric IVC suggests fluid overload; collapsed IVC suggests dehydration (less common)

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Management

Immediate Management (First 10 minutes)

1. **A, B, C resuscitation** - High-flow oxygen (target SpO2 92-96%), large-bore IV access (2x 16-18G), cardiac monitoring
2. **IV fluids** - 1-2 L Hartmann's or 0.9% NaCl rapid bolus (most patients are volume depleted from diaphoresis, vomiting, diarrhoea)
3. **Cooling measures** - Paracetamol 1 g IV, active cooling (ice packs, cooling blankets, tepid sponging); **AVOID ASPIRIN** (displaces thyroid hormone from binding proteins)
4. **Bloods + ECG** - TFTs, FBC, UEC, LFTs, troponin, VBG, lactate, blood cultures, ECG, CXR
5. **Activate ICU** - All thyroid storm patients require ICU admission

Resuscitation (Multi-Modal "Five-Step" Therapy)

The management of thyroid storm follows a sequential five-step approach to block thyroid hormone synthesis, release, and peripheral action [21,22]:

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STEP 1: Block New Hormone Synthesis (Thionamides)

Propylthiouracil (PTU) - PREFERRED in thyroid storm (also blocks T4→T3 conversion peripherally)

Carbimazole (or Methimazole) - Alternative if PTU unavailable

Rationale: Thionamides inhibit thyroid peroxidase (TPO), blocking iodination and coupling of thyroglobulin → prevents NEW thyroid hormone synthesis. PTU also inhibits 5'-deiodinase (peripheral T4→T3 conversion), making it superior in acute crisis [23].

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STEP 2: Block Hormone Release (Iodine Therapy)

CRITICAL TIMING: Administer iodine ≥1 hour AFTER first thionamide dose to prevent iodine being used as substrate for new hormone synthesis (Wolff-Chaikoff effect) [24].

Rationale: High-dose iodine acutely inhibits thyroid hormone release from the thyroid gland (Wolff-Chaikoff effect) and blocks organification. Must give AFTER thionamides to avoid providing substrate for synthesis [25].

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STEP 3: Block Peripheral Thyroid Hormone Action (Beta-Blockade)

Propranolol - PREFERRED (non-selective β-blocker; high doses block T4→T3 conversion)

Esmolol - Alternative (ultra-short-acting β-blocker for ICU)

Contraindications to beta-blockade: Severe decompensated heart failure, bronchospasm (asthma, COPD), heart block

Alternative if beta-blocker contraindicated:

• Diltiazem 60 mg PO q6h or 5-10 mg IV (calcium channel blocker for rate control)
• Reserpine 2.5-5 mg IM q4-6h (rarely available; depletes catecholamines)

Rationale: Beta-blockade reduces peripheral effects of thyroid hormones (tachycardia, tremor, agitation) and blocks T4→T3 conversion. Propranolol at high doses (greater than 160 mg/day) inhibits 5'-deiodinase [26,27].

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STEP 4: Block Peripheral T4→T3 Conversion (Corticosteroids)

Hydrocortisone - PREFERRED (also treats potential relative adrenal insufficiency)

Dexamethasone - Alternative

Rationale: Corticosteroids inhibit peripheral T4→T3 conversion (5'-deiodinase) and treat potential relative adrenal insufficiency associated with severe thyrotoxicosis. Also reduce T3 binding to nuclear receptors [28,29].

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STEP 5: Identify and Treat Precipitant

Common precipitants (present in ~80% of cases):

• Infection (40-50%): Pneumonia, UTI, sepsis → IV antibiotics (e.g., ceftriaxone 1-2 g IV, piperacillin-tazobactam 4.5 g IV q8h)
• Non-compliance with antithyroid drugs (20-30%) → Resume medications
• Surgery or trauma (10-20%) → Post-operative care, analgesia
• Radioiodine therapy (RAI) (5-10%) → Supportive care
• Iodine exposure (contrast media, amiodarone) → Avoid further iodine
• Diabetic ketoacidosis (DKA) (5%) → Insulin, IV fluids
• Myocardial infarction (5%) → Cardiology consultation, antiplatelet therapy
• Cerebrovascular accident (CVA) (2-5%) → CT brain, neurology
• Medication interactions (pseudoephedrine, salicylates)

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Supportive Care

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Refractory Cases (No Improvement in 24-48 Hours)

If patient deteriorates despite maximal medical therapy:

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Definitive Care

• ICU admission: Mandatory for all confirmed thyroid storm cases
• Endocrinology consultation: Urgent review within 24 hours; plan long-term management (RAI vs surgery vs long-term antithyroid drugs)
• Cardiology: If heart failure, atrial fibrillation, or myocardial ischaemia
• Psychiatry: If severe agitation, psychosis requires ongoing sedation

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Disposition

Admission Criteria

ALL patients with thyroid storm require ICU admission:

• Burch-Wartofsky score ≥45
• Multi-organ dysfunction (cardiac, CNS, hepatic)
• Haemodynamic instability (hypotension, AF with RVR greater than 150 bpm)
• Altered mental status (GCS below 13)
• Temperature greater than 40°C

ICU/HDU Criteria

Indications for ICU:

• All confirmed thyroid storm (BWPS ≥45)
• Impending storm (BWPS 25-44) with any of: hypotension, heart failure, severe agitation, GCS below 13
• Requirement for invasive monitoring (arterial line, CVP), vasopressors, intubation
• Atrial fibrillation with RVR greater than 150 bpm despite beta-blockade
• Refractory hyperpyrexia (greater than 40°C)

Discharge Criteria

No patient with thyroid storm is discharged from ED. For impending storm (BWPS 25-44) without critical features:

• Admit to monitored bed (ward or HDU)
• Initiate five-step therapy
• Serial observations (HR, BP, temp q1h)
• Daily TFTs to monitor response
• Endocrinology review within 24 hours

Follow-up

• Post-discharge (weeks later after ICU discharge):
• Endocrinology outpatient review within 1-2 weeks
• Repeat TFTs at 1 week, 2 weeks, 4 weeks (adjust antithyroid drug dose)
• Plan definitive therapy: Radioiodine ablation (RAI) or thyroidectomy (prevent recurrence)
• Cardiology follow-up if heart failure or persistent AF (anticoagulation, rate/rhythm control)
• GP letter detailing: diagnosis, precipitant, treatment, long-term plan, red flags to return

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Special Populations

Paediatric Considerations

• Thyroid storm is rare in children but can occur with Graves' disease
• Age-specific dosing:
  • "PTU: 5-10 mg/kg/dose PO q6h (max 300 mg/dose)"
  • "Carbimazole: 0.5-1 mg/kg/day divided q8h"
  • "Propranolol: 0.5-1 mg/kg/dose PO q6h (max 40 mg/dose)"
  • "Hydrocortisone: 1-2 mg/kg IV q6h (max 100 mg/dose)"
• Lugol's iodine: 1 drop per 10 kg (max 10 drops) q8h

Pregnancy

• Thyroid storm in pregnancy is life-threatening to mother and fetus (maternal mortality 25%, fetal loss 25%)
• PTU is preferred in 1st trimester (lower risk of congenital anomalies vs carbimazole); switch to carbimazole in 2nd/3rd trimester (lower risk of hepatotoxicity)
• Beta-blockers: Propranolol safe but may cause fetal bradycardia, IUGR; use lowest effective dose
• Avoid radioiodine (contraindicated in pregnancy/lactation)
• Obstetric consultation: Fetal monitoring (CTG), assess for preterm labour, consider delivery if fetal distress
• Post-partum: Risk of neonatal thyrotoxicosis (maternal TRAb crosses placenta) → neonatal TFTs, paediatric endocrinology [34,35]

Elderly

• Thyroid storm in elderly often presents atypically ("apathetic thyrotoxicosis"): lethargy, depression, minimal hyperactivity
• Higher risk of atrial fibrillation (35-50%), heart failure, and cardiovascular collapse
• Lower threshold for ICU admission
• Anticoagulation for AF if no contraindications (DOAC or warfarin)
• Increased sensitivity to beta-blockers → start low dose (propranolol 20 mg PO q6h)

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori considerations:

• Health disparities: Aboriginal and Torres Strait Islander peoples have higher rates of cardiovascular disease (2-3x higher), diabetes, and chronic kidney disease, which may complicate thyroid storm management [36]
• Iodine nutrition: Remote Indigenous communities may have iodine deficiency (less access to iodised salt, seafood), affecting thyroid disorders; conversely, some coastal communities have adequate iodine intake [37]
• Access barriers: Remote areas have limited access to endocrinology, ICU, and definitive therapy (RAI, surgery); early retrieval (RFDS) is critical [38]
• Cultural safety: Involve Aboriginal Health Workers, Torres Strait Islander Health Workers, or Māori health practitioners; ensure whānau (family) involvement in decision-making; respect cultural protocols for communication
• Interpreter services: Engage accredited interpreters for non-English speaking patients; avoid family members as interpreters for clinical discussions

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Resuscitation - Thyroid Storm Management

Format: Resuscitation/Team Leadership Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are the ED registrar. A 40-year-old woman has been brought in by ambulance with fever, agitation, and palpitations. She has a history of Graves' disease but stopped her medication 3 weeks ago. The nurse has placed her in the resuscitation bay and attached monitoring. The RN, intern, and consultant are available. Please assess and manage this patient.

Examiner Instructions:

• Patient presents with thyroid storm (BWPS ~75 points)
• Observations: GCS 13 (E3 V4 M6), HR 155 bpm (irregular), BP 150/60 mmHg, temp 39.9°C, RR 30/min, SpO2 93% RA
• Physical exam: Diaphoretic, tremulous, large diffuse goitre, exophthalmos, warm peripheries
• Expects candidate to: (1) Recognise thyroid storm, (2) Initiate ABCDE resuscitation, (3) Calculate BWPS, (4) Start five-step therapy in correct sequence, (5) Activate ICU, (6) Demonstrate team leadership

Actor/Patient Brief:

• You are a 40-year-old woman with Graves' disease
• You stopped taking carbimazole 3 weeks ago because you "felt better" and didn't think you needed it
• You've had 2 days of fever, palpitations, diarrhoea, and feeling "jittery"
• You are confused, agitated, and keep trying to get off the bed
• Answer questions briefly and repetitively ("I'm hot"
  • "My heart is racing")

Marking Criteria:

Expected Standard:

• Pass: ≥10/17
• Key discriminators:
  • Recognising diagnosis (thyroid storm vs sepsis vs other)
  • Correct sequencing (thionamides BEFORE iodine)
  • Avoiding aspirin
  • ICU activation

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Station 2: Communication - Discussing ICU Admission with Family

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

Candidate Instructions:

You are the ED consultant. You have just assessed a 45-year-old woman with thyroid storm (confirmed diagnosis, BWPS 80). She is confused and haemodynamically unstable despite initial resuscitation. Her husband is waiting in the relatives' room and is very anxious. Please explain the diagnosis, management plan, and need for ICU admission.

Examiner Instructions:

• Husband is anxious, tearful, and struggles to understand medical terminology
• He asks: "Is she going to die?"
  • "What caused this?"
  • "Why didn't her GP pick this up?"
• Expects candidate to: (1) Introduce self, explain diagnosis in lay terms, (2) Explain severity and need for ICU, (3) Outline treatment plan, (4) Address concerns empathetically, (5) Check understanding

Actor Brief (Husband):

• You are the patient's husband; married 15 years, 2 children (aged 8 and 11)
• Your wife has had Graves' disease for 5 years; she was on medication but stopped it 4 weeks ago because she "felt fine"
• You are very worried and keep asking "Is she going to die?"
• You are angry at her GP for "not monitoring her properly"
• You have limited medical knowledge; need explanations in simple language

Marking Criteria:

Expected Standard:

• Pass: ≥9/15
• Key discriminators:
  • Empathy and honesty about severity
  • Plain language (avoiding medical jargon)
  • Addressing "Is she going to die?" directly but compassionately

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Station 3: Data Interpretation - Investigating Hyperthyroid Crisis

Format: Data Interpretation Time: 11 minutes Setting: ED clinical workstation

Candidate Instructions:

A 55-year-old man presents with fever (39.5°C), tachycardia (HR 140 bpm), and confusion. You suspect thyroid storm. Review the investigation results provided and answer the examiner's questions.

Examiner Instructions: Provide candidate with investigation results (printed):

Bloods:

• TSH below 0.01 mU/L (normal 0.5-5.0)
• Free T4 95 pmol/L (normal 10-20)
• Free T3 32 pmol/L (normal 3-7)
• WCC 16 x 10^9/L, neutrophils 14
• Na 132 mmol/L, K 3.1 mmol/L, Cl 98 mmol/L
• Urea 12 mmol/L, Cr 145 μmol/L (baseline 80)
• Glucose 8.5 mmol/L
• ALT 120 U/L, AST 95 U/L, ALP 250 U/L, bilirubin 35 μmol/L
• Corrected Ca 2.75 mmol/L (normal 2.1-2.6)
• Troponin I 85 ng/L (normal below 30)
• Lactate 3.5 mmol/L

VBG: pH 7.32, pCO2 30 mmHg, HCO3 18 mmol/L, BE -6

ECG: Atrial fibrillation, ventricular rate 140 bpm, ST depression in V4-V6 (1 mm)

CXR: Cardiomegaly, upper lobe blood diversion, Kerley B lines (mild pulmonary oedema)

Questions for candidate:

1. Interpret the TFTs and explain the diagnosis.
2. What is the significance of the elevated troponin and ECG changes?
3. Interpret the VBG. What acid-base disturbance is present?
4. What is the significance of the hypokalaemia and hypercalcaemia?
5. What does the elevated bilirubin and transaminases suggest?

Marking Criteria:

Expected Standard:

• Pass: ≥9/15
• Key discriminators:
  • Recognising demand ischaemia (troponin/ST changes) vs ACS
  • Mixed acid-base interpretation
  • Linking hypercalcaemia to thyrotoxicosis (increased bone resorption)

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SAQ Practice

Question 1 (8 marks)

Stem: A 42-year-old woman presents to ED with fever (40°C), confusion (GCS 12), tachycardia (HR 150 bpm, atrial fibrillation), and diarrhoea. She has a large goitre. You diagnose thyroid storm.

Question: Outline the five-step multi-modal therapy for thyroid storm, including drug names, doses, routes, and the rationale for each step. (8 marks)

Model Answer:

1. STEP 1: Block thyroid hormone synthesis (2 marks)

   • Propylthiouracil (PTU) 500-1000 mg PO/NG loading, then 250 mg q4h (1 mark)
   • Rationale: Inhibits thyroid peroxidase (TPO) → blocks NEW hormone synthesis; PTU also blocks T4→T3 conversion peripherally (1 mark)

2. STEP 2: Block thyroid hormone release (2 marks)

   • Lugol's iodine 5-10 drops (0.25-0.5 mL) PO q8h, given ≥1 hour AFTER first PTU dose (1 mark)
   • Rationale: Inhibits hormone release via Wolff-Chaikoff effect; must give AFTER thionamides to prevent iodine being used as substrate for synthesis (1 mark)

3. STEP 3: Block peripheral thyroid hormone action (1 mark)

   • Propranolol 40-80 mg PO q4-6h OR 1-2 mg IV slow push (0.5 marks)
   • Rationale: Beta-blockade controls tachycardia, tremor, agitation; propranolol at high doses also blocks T4→T3 conversion (0.5 marks)

4. STEP 4: Block peripheral T4→T3 conversion and treat adrenal insufficiency (2 marks)

   • Hydrocortisone 100 mg IV q8h (1 mark)
   • Rationale: Inhibits 5'-deiodinase (T4→T3 conversion); treats relative adrenal insufficiency in severe thyrotoxicosis (1 mark)

5. STEP 5: Identify and treat precipitant (1 mark)

   • Common precipitants: infection (most common), non-compliance with antithyroid drugs, surgery, trauma, RAI, DKA, MI
   • Management: Blood cultures + empiric IV antibiotics (e.g., ceftriaxone 2 g IV) if infection suspected (1 mark)

Examiner Notes:

• Accept: Carbimazole 40-60 mg instead of PTU (but note PTU is preferred)
• Accept: SSKI 5 drops q6h instead of Lugol's
• Accept: Esmolol IV infusion instead of propranolol (for ICU setting)
• Do not accept: Iodine given BEFORE thionamides (critical error)
• Do not accept: Aspirin for fever (worsens thyrotoxicosis)

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Question 2 (6 marks)

Stem: A 50-year-old man with suspected thyroid storm has a Burch-Wartofsky Point Scale (BWPS) score of 55.

Question: List the six domains assessed in the Burch-Wartofsky Point Scale and the maximum points for each domain. (6 marks)

Model Answer:

1. Temperature - Maximum 30 points (temp ≥40°C) (1 mark)
2. CNS effects - Maximum 30 points (severe: seizures or coma) (1 mark)
3. Tachycardia - Maximum 25 points (HR ≥140 bpm) (1 mark)
4. Atrial fibrillation - Maximum 10 points (if present) (1 mark)
5. Heart failure - Maximum 15 points (severe: pulmonary oedema) (1 mark)
6. GI/hepatic dysfunction - Maximum 20 points (severe: jaundice) (1 mark)

BONUS: Precipitant history - 10 points (if positive history of precipitating event)

Interpretation:

• ≥45 points: Highly suggestive of thyroid storm
• 25-44 points: Impending thyroid storm
• below 25 points: Unlikely thyroid storm

Examiner Notes:

• Accept specific point values for each parameter (e.g., "Temperature: 37.2-37.7°C = 5 points; 37.8-38.2°C = 10 points..." etc.) for full marks
• Accept "precipitant" as 7th domain (10 points)
• Do not accept vague answers (e.g., "cardiovascular" without specifying tachycardia, AF, heart failure separately)

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Question 3 (6 marks)

Stem: You are managing a patient with thyroid storm in a resource-limited remote hospital. Propylthiouracil (PTU) is not available.

Question: Describe three alternative strategies to manage this patient's thyroid storm when PTU is unavailable, including drug names and doses. (6 marks)

Model Answer:

1. Use carbimazole (thionamide alternative) (2 marks)

   • Carbimazole 40-60 mg PO loading, then 15-30 mg q6h (1 mark)
   • Rationale: Blocks thyroid hormone synthesis (inhibits TPO) but does NOT block peripheral T4→T3 conversion (unlike PTU); less ideal but better than nothing (1 mark)

2. Add oral cholecystographic contrast agent (if available) (2 marks)

   • Ipodate or iopanoic acid 500 mg-1 g PO daily (1 mark)
   • Rationale: Contains iodine (blocks hormone release) AND inhibits 5'-deiodinase (blocks T4→T3 conversion), partially compensating for lack of PTU (1 mark)

3. Optimise other steps of five-step therapy (2 marks)

   • Lugol's iodine 5-10 drops q8h (≥1 hour after carbimazole) to block hormone release (0.5 marks)
   • High-dose propranolol 80 mg PO q4h (or IV 1-2 mg slow push q10-15 min) - high doses block T4→T3 conversion (0.5 marks)
   • Hydrocortisone 100 mg IV q8h to block T4→T3 conversion (0.5 marks)
   • Supportive care: Aggressive cooling, IV fluids, electrolyte replacement, treat precipitant (0.5 marks)

Examiner Notes:

• Accept methimazole instead of carbimazole (same drug; carbimazole is pro-drug of methimazole)
• Accept "use Betadine (povidone-iodine) solution" as alternative iodine source if Lugol's unavailable (unconventional but reported in literature)
• Accept "arrange urgent retrieval (RFDS)" as part of management plan for resource-limited setting
• Do not accept "just wait for PTU to arrive"
• must initiate alternative therapy

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Question 4 (8 marks)

Stem: A 48-year-old woman with thyroid storm remains febrile (39.8°C), tachycardic (HR 135 bpm), and hypotensive (BP 85/50 mmHg) despite 48 hours of maximal medical therapy (PTU, iodine, propranolol, hydrocortisone).

Question: List four extracorporeal or surgical rescue therapies for refractory thyroid storm and briefly describe the mechanism and evidence for plasmapheresis. (8 marks)

Model Answer:

Four rescue therapies (4 marks - 1 mark each):

1. Plasmapheresis (therapeutic plasma exchange)
2. Haemoperfusion (charcoal or resin column adsorption)
3. Emergency thyroidectomy (total or subtotal)
4. ECMO (veno-arterial extracorporeal membrane oxygenation) for cardiovascular collapse

Plasmapheresis - Mechanism and Evidence (4 marks):

Mechanism (2 marks):

• Physically removes circulating thyroid hormones (T4, T3) and thyroid-stimulating immunoglobulins (TRAb in Graves' disease) from plasma by exchanging 1-1.5 plasma volumes (3-5 litres) with albumin or FFP (1 mark)
• Reduces T4/T3 levels by 30-60% per session; typically 1-3 sessions over 24-72 hours (1 mark)

Evidence (2 marks):

• No RCTs exist (thyroid storm is rare; ethical challenges of randomising critically ill patients) (0.5 marks)
• Case series and case reports show clinical improvement in 70-80% of refractory cases, with more rapid decline in T4/T3 compared to medical therapy alone (1 mark)
• Indications: Multi-organ failure, refractory hyperthermia, rising free T4/T3 despite maximal therapy, failure to improve by 24-48 hours (0.5 marks)

Examiner Notes:

• Accept "continuous renal replacement therapy (CRRT)" as alternative to haemoperfusion (less effective than plasmapheresis but may remove some hormone)
• Accept "cholestyramine" (bile acid sequestrant; binds thyroid hormones in gut, interrupts enterohepatic circulation) as medical rescue therapy
• Do not accept "increase dose of medications"
• question asks for extracorporeal/surgical therapies
• Full marks require BOTH mechanism AND evidence for plasmapheresis

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Australian Guidelines

ARC/ANZCOR

• Not applicable - Thyroid storm is not covered by ARC/ANZCOR guidelines (focus on resuscitation, cardiac arrest)
• Relevant ANZCOR guidelines:
  • "ANZCOR Guideline 11.10: Post-resuscitation care (if thyroid storm patient suffers cardiac arrest)"
  • "ANZCOR Guideline 11.7: Acute coronary syndromes (relevant for managing myocardial ischaemia in thyroid storm)"

Therapeutic Guidelines Australia

Therapeutic Guidelines: Endocrinology (Version 6, 2021):

• Thyroid storm management:
  • "First-line thionamide: Propylthiouracil (PTU) 500-1000 mg loading, then 250 mg q4h PO"
  • "Alternative: Carbimazole 40-60 mg loading, then 15-30 mg q6h (if PTU unavailable or contraindicated)"
  • "Iodine: Lugol's iodine 5-10 drops TDS, given ≥1 hour after thionamide"
  • "Beta-blocker: Propranolol 40-80 mg PO q4-6h (preferred) or atenolol 50 mg PO q12h"
  • "Corticosteroid: Hydrocortisone 100 mg IV q8h or dexamethasone 2 mg IV q6h"
  • "Supportive: Paracetamol (NOT aspirin), IV fluids, cooling, treat precipitant"

Cardiovascular Therapeutic Guidelines (Version 7, 2022):

• Atrial fibrillation in thyrotoxicosis:
  • "Rate control: Beta-blockers first-line (propranolol, metoprolol)"
  • "Anticoagulation: Consider if AF greater than 48 hours or CHA2DS2-VASc ≥2 (thyrotoxic AF has stroke risk similar to other AF)"
  • "Rhythm control: Defer until euthyroid (electrical cardioversion often fails in thyrotoxicosis; spontaneous reversion to sinus rhythm common once euthyroid)"

State-Specific Guidelines

NSW Health:

• Thyroid Storm Clinical Pathway (not widely published; local ICU protocols vary)
• HealthPathways Sydney: Recommends endocrinology consultation within 24 hours, ICU admission mandatory

Victoria:

• Austin Health Endocrinology Protocols: Five-step therapy as above; plasmapheresis available at Alfred, Austin, Monash

Queensland:

• Queensland Health Endocrine Emergencies Guideline (2020): Similar to Therapeutic Guidelines; emphasises early ICU, RFDS retrieval for remote patients

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Remote/Rural Considerations

Pre-Hospital

• Paramedic recognition: Difficult (non-specific presentation); may be called for "?sepsis"
  • "?psychosis"
  • "?cardiac arrest"
• Pre-hospital management: Limited options (oxygen, IV access, IV fluids, transport to hospital); no specific thyroid storm therapy in ambulance
• Communication: Paramedics should pre-notify ED if suspected hypermetabolic crisis (fever + tachycardia + agitation + known thyroid history)

Resource-Limited Setting (Remote Hospital)

Challenges:

• Limited pharmacy: PTU rarely stocked (may have carbimazole); Lugol's iodine may be unavailable (use Betadine solution as alternative); propranolol usually available
• No ICU: Patient requires retrieval to tertiary centre; stabilisation in ED until RFDS arrives (4-12 hours)
• Limited investigations: TFTs may take 24-72 hours (sent to distant lab); must treat empirically based on clinical diagnosis (BWPS)
• No endocrinology: Telemedicine consultation (NT Virtual EM, QLD Telehealth) essential for specialist advice

Adapted management:

1. Diagnose clinically (BWPS ≥45) - do NOT wait for TFTs
2. Activate RFDS immediately (1800 625 800 or local base)
3. Initiate five-step therapy with available resources:
   • Carbimazole if no PTU
   • Betadine solution if no Lugol's iodine
   • Propranolol (usually stocked)
   • Hydrocortisone (usually stocked for adrenal crisis)
4. Supportive care: IV fluids, paracetamol, cooling, treat precipitant (empiric antibiotics if infection suspected)
5. Monitor closely: q15 min obs; prepare for deterioration
6. Handover to RFDS: Comprehensive written + verbal handover

Retrieval (RFDS)

Indications for retrieval:

• ALL thyroid storm patients in remote hospitals without ICU
• Impending storm (BWPS 25-44) if unable to monitor or no HDU beds

RFDS capabilities:

• Advanced airway (intubation, mechanical ventilation)
• Vasopressors (metaraminol, adrenaline)
• Cardiac monitoring
• Telehealth link to intensivist (real-time advice during transport)
• IV medications (propranolol IV, hydrocortisone IV, antibiotics)

Retrieval timeframe:

• Activation to arrival: 2-6 hours (depends on distance, weather, aircraft availability)
• Stabilisation on ground: 30-60 minutes (RFDS doctor/flight nurse assess, optimise, prepare for flight)
• Flight to tertiary centre: 1-4 hours (e.g., Alice Springs to Adelaide 2.5 hours, Broken Hill to Sydney 2 hours)

Preparation for retrieval:

• Stabilise patient (ABCDE, five-step therapy, IV access x2, NG tube if required)
• Handover documentation: Medications given (drug, dose, time), observations chart, investigation results, ECG, imaging
• Communication: ED → RFDS → receiving ICU (three-way handover)

Telemedicine

Services:

• NT Virtual Emergency Medicine Service (NT VEMS): 24/7 telehealth support for remote NT hospitals; ED consultant + ICU registrar available
• Queensland Virtual Rural Generalist Service (QVRGS): Specialist teleconsultation for rural/remote Queensland EDs
• WA Country Health Service Telehealth: Endocrinology, ICU, ED teleconsultation

Use in thyroid storm:

• ED initial assessment: Telehealth consult with endocrinologist or intensivist to confirm diagnosis, refine management
• During retrieval: RFDS can consult intensivist en route for real-time decision-making (e.g., intubation, vasopressor dose adjustment)
• Post-discharge: Remote follow-up (TFT monitoring, medication titration) via telehealth reduces need for patient to travel

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References

Guidelines

1. Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from the Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J. 2016;63(12):1025-1064. PMID: 27916783
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343-1421. PMID: 27521067
3. Therapeutic Guidelines Ltd. Therapeutic Guidelines: Endocrinology. Version 6. Melbourne: Therapeutic Guidelines Limited; 2021.

Key Evidence

4. Chiha M, Samarasinghe S, Kabaker AS. Thyroid storm: an updated review. J Intensive Care Med. 2015;30(3):131-140. PMID: 23920160
5. Akamizu T, Satoh T, Isozaki O, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012;22(7):661-679. PMID: 22690898
6. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263-277. PMID: 8325286
7. Angell TE, Lechner MG, Nguyen CT, et al. Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study. J Clin Endocrinol Metab. 2015;100(2):451-459. PMID: 25343234
8. Ono Y, Ono S, Yasunaga H, et al. Clinical characteristics and outcomes of thyroid storm: analysis of a Japanese nationwide emergency department database. Eur Thyroid J. 2017;6(3):130-136. PMID: 28589091
9. Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am. 1995;79(1):169-184. PMID: 7808088
10. Australian Institute of Health and Welfare. Thyroid disorders in Australia 2020. Cat. no. PHE 267. Canberra: AIHW; 2020.
11. Lucas RM, Valery PC, van der Mei I, et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology. 2011;76(6):540-548. PMID: 21300969
12. Zhao Y, Russell DJ, Guthridge S, et al. Long-term trends in supply and sustainability of the health workforce in remote Aboriginal communities in the Northern Territory. BMC Health Serv Res. 2017;17(1):836. PMID: 29258520

Pathophysiology and Clinical Features

13. Silva JE. Thyroid hormone control of thermogenesis and energy balance. Thyroid. 1995;5(6):481-492. PMID: 8808101
14. Wartofsky L. Clinical criteria for the diagnosis of thyroid storm. Thyroid. 2012;22(7):659-660. PMID: 22690900
15. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116(15):1725-1735. PMID: 17923583
16. Haber RS, Loeb JN. Stimulation of potassium efflux in rat liver by a low dose of thyroid hormone: evidence for enhanced cation permeability in the absence of Na,K-ATPase induction. Endocrinology. 1986;118(1):207-211. PMID: 3000739
17. Bauer M, Goetz T, Glenn T, Whybrow PC. The thyroid-brain interaction in thyroid disorders and mood disorders. J Neuroendocrinol. 2008;20(10):1101-1114. PMID: 18673411
18. Doran GR. Serum enzyme disturbances in thyrotoxicosis and hypothyroidism. J R Soc Med. 1978;71(11):798-802. PMID: 731677

Management: Thionamides and Iodine

19. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35(4):663-686. PMID: 17127140
20. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263-277. PMID: 8325286
21. Nayak B, Hodak SP. Hyperthyroidism. Endocrinol Metab Clin North Am. 2007;36(3):617-656. PMID: 17673121
22. Carroll R, Matfin G. Endocrine and metabolic emergencies: thyroid storm. Ther Adv Endocrinol Metab. 2010;1(3):139-145. PMID: 23148161
23. Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905-917. PMID: 15745981
24. Wolff J, Chaikoff IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem. 1948;174(2):555-564. PMID: 18865621
25. Burman KD, Wartofsky L. Iodine effects on the thyroid gland: biochemical and clinical aspects. Rev Endocr Metab Disord. 2000;1(1-2):19-25. PMID: 11704989

Management: Beta-Blockers and Steroids

26. Migneco A, Ojetti V, Testa A, et al. Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005;9(1):69-74. PMID: 15852520
27. Mackin JF, Canary JJ, Pittman CS. Thyroid storm and its management. N Engl J Med. 1974;291(26):1396-1398. PMID: 4427641
28. Tsatsoulis A, Johnson EO, Kalogera CH, et al. The effect of thyrotoxicosis on adrenocortical reserve. Eur J Endocrinol. 2000;142(3):231-235. PMID: 10700716
29. Wartofsky L, Burman KD. Alterations in thyroid function in patients with systemic illness: the "euthyroid sick syndrome". Endocr Rev. 1982;3(2):164-217. PMID: 6806085
30. Patel H, Toft AD. Thyrotoxic crisis. Postgrad Med J. 1988;64(752):444-447. PMID: 3077590

Rescue Therapies

31. Ezer A, Caliskan K, Parlakgumus A, et al. Preoperative therapeutic plasma exchange in patients with thyrotoxicosis. J Clin Apher. 2009;24(3):111-114. PMID: 19373855
32. Muller C, Perrin P, Faller B, et al. Role of plasma exchange in the thyroid storm. Ther Apher Dial. 2011;15(6):522-531. PMID: 22107689
33. Merhige ME, Schussler GC, Hershman JM. Emergency subtotal thyroidectomy for thyroid storm. Thyroid. 1995;5(6):513-517. PMID: 8808106

Pregnancy and Special Populations

34. Millar LK, Wing DA, Leung AS, et al. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet Gynecol. 1994;84(6):946-949. PMID: 7970474
35. Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol. 2006;108(5):1283-1292. PMID: 17077257

Indigenous Health

36. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander Health Performance Framework 2020 summary report. Cat. no. IHPF 2. Canberra: AIHW; 2020.
37. McDonnell CM, Harris M, Zacharin MR. Iodine deficiency and goitre in schoolchildren in Melbourne, 2001. Med J Aust. 2003;178(4):159-162. PMID: 12580737
38. Zhao Y, Russell DJ, Guthridge S, et al. Costs and effects of higher turnover of nurses and Aboriginal health practitioners and higher use of short-term nurses in remote Australian primary care services: an observational cohort study. BMJ Open. 2019;9(6):e023906. PMID: 31248931

Additional Key References

39. Angell TE, Lechner MG, Nguyen CT, et al. Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study. J Clin Endocrinol Metab. 2015;100(2):451-459. PMID: 25343234
40. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2019;74(1):104-132. PMID: 30703431