Phaeochromocytoma Crisis

Quick Answer

Phaeochromocytoma crisis is a life-threatening hyperadrenergic state caused by massive catecholamine release from a chromaffin cell tumour of the adrenal medulla (phaeochromocytoma) or extra-adrenal paraganglia (paraganglioma). Catecholamines are synthesized via the pathway: Tyrosine → L-DOPA → Dopamine → Noradrenaline → Adrenaline with tyrosine hydroxylase as the rate-limiting enzyme. Crisis presents with severe hypertension (SBP >200 mmHg), tachycardia, diaphoresis, headache, and pallor. Alpha-adrenergic receptors mediate vasoconstriction; beta-adrenergic receptors mediate tachycardia and increased inotropy. CRITICAL PRINCIPLE: Alpha-blockade MUST precede beta-blockade to prevent unopposed alpha-mediated vasoconstriction. Phenoxybenzamine (non-competitive, irreversible α-blocker) is first-line for pre-operative optimization (10-14 days), with phentolamine for acute crisis. Beta-blockade (esmolol, propranolol) is ONLY added after adequate alpha-blockade. Plasma metanephrines have 96-99% sensitivity for diagnosis. Up to 40% of cases are hereditary (MEN2/VHL/SDH mutations). Post-resection hypotension from catecholamine withdrawal is common and may require aggressive fluid resuscitation and vasopressor support. ICU mortality in properly managed elective cases is less than 2%; emergency resection carries 20-30% mortality.[1-5]

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CICM Exam Focus

Second Part Written Exam

Phaeochromocytoma crisis is a high-yield CICM topic with strong links to applied pharmacology and perioperative medicine:

Common SAQ Topics

• "Outline the catecholamine biosynthesis pathway and identify the rate-limiting step"
• "Describe the pre-operative optimization protocol for a patient with phaeochromocytoma"
• "Explain why alpha-blockade must precede beta-blockade in phaeochromocytoma management"
• "Discuss the intraoperative management of hypertensive crisis during phaeochromocytoma resection"
• "Outline the ICU management of post-resection hypotension"
• "Compare MEN2, VHL, and SDH-related phaeochromocytoma syndromes"

Viva Scenarios

• Managing acute phaeochromocytoma crisis in an undiagnosed patient presenting with hypertensive emergency
• Pre-operative optimization: alpha vs beta-blockade sequencing and targets
• Intraoperative hypertensive crisis management and pharmacological options
• Post-resection hypotension and hypoglycaemia - pathophysiology and management
• Genetics of phaeochromocytoma - when to test and implications for family screening
• Communication with family regarding perioperative risks

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Key Points

Clinical

1. Catecholamine Synthesis Pathway: Tyrosine → L-DOPA (tyrosine hydroxylase, rate-limiting) → Dopamine (AADC) → Noradrenaline (dopamine β-hydroxylase) → Adrenaline (PNMT)

2. Alpha-Blockade FIRST - NEVER Beta Before Alpha: Beta-blockers cause unopposed alpha vasoconstriction → paradoxical hypertensive crisis → stroke, MI, death

3. Phenoxybenzamine: Non-competitive, irreversible α1 and α2 blocker; 10-14 days pre-operatively; causes reflex tachycardia (hence need for later beta-blockade)

4. Phentolamine: Competitive, reversible α1 and α2 blocker; used for acute intraoperative hypertensive crisis; bolus 2-5 mg IV, infusion 1-5 mg/h

5. Plasma Metanephrines: Sensitivity 96-99%, specificity 85-89%; metanephrine (from adrenaline), normetanephrine (from noradrenaline)

6. Hereditary Syndromes (40%): MEN2 (RET - adrenergic, bilateral), VHL (noradrenergic), SDHB (highest malignancy risk 30-70%)

7. Pre-operative Optimization Goals: BP less than 130/80 sitting, orthostatic BP drop less than 20 mmHg, HR 60-80/min, no new ST-T changes, volume-expanded (high-salt diet, IV fluids)

8. Intraoperative Crisis: Tumour manipulation → massive catecholamine release → SBP >250 mmHg → phentolamine bolus + nitroprusside/magnesium infusion

9. Post-Resection Hypotension: Abrupt catecholamine withdrawal → vasodilation → hypotension; requires aggressive fluid resuscitation ± vasopressors (noradrenaline)

10. Post-Resection Hypoglycaemia: Catecholamines normally inhibit insulin release; removal → rebound hyperinsulinaemia → hypoglycaemia; monitor BSL hourly for 24-48h

Memory Aid: "ALPHA FIRST"

• A - Alpha-blockade ALWAYS before beta-blockade

• L - Long-acting phenoxybenzamine (10-14 days pre-op)

• P - Phentolamine for acute crisis (fast-acting, reversible)

• H - Heart rate control with beta-blocker AFTER alpha-blockade

• A - Avoid unopposed alpha vasoconstriction

• F - Fluid loading pre-operatively (volume expansion)

• I - ICU post-operatively for monitoring

• R - Resection may cause profound hypotension

• S - Sugar (glucose) monitoring for hypoglycaemia

• T - Test genetics (40% hereditary - MEN2/VHL/SDH)

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Definition & Epidemiology

Definition

Phaeochromocytoma is a catecholamine-secreting tumour arising from chromaffin cells of the adrenal medulla (80-85%) or extra-adrenal sympathetic paraganglia (15-20%, termed paraganglioma).[6,7]

Phaeochromocytoma crisis is an acute, life-threatening hyperadrenergic state characterized by:

• Severe paroxysmal or sustained hypertension (SBP >180-200 mmHg)
• Tachycardia, palpitations, arrhythmias
• Diaphoresis, pallor, tremor
• Headache, anxiety, sense of impending doom
• End-organ damage: stroke, MI, pulmonary oedema, aortic dissection

The "Rule of 10s"

• Now Outdated

Traditional teaching suggested 10% of phaeochromocytomas were:

• Malignant
• Bilateral
• Extra-adrenal
• Familial
• Paediatric

Contemporary data shows higher rates:

• Malignant: 10-15% (up to 70% with SDHB mutations)[8]
• Bilateral: 10-20% (higher in hereditary syndromes)
• Extra-adrenal: 15-25%
• Familial/Hereditary: 35-40%[9]
• Paediatric: 10-20%

Epidemiology

International Data:

• Incidence: 2-8 per million population per year[10]
• Prevalence among hypertensive patients: 0.1-0.6%[11]
• Peak incidence: 40-50 years of age
• Sex distribution: Equal (M:F = 1:1)
• Incidental discovery ("incidentaloma"): 25-50% of cases[12]

Australian/NZ Data:

• Estimated 100-200 new cases per year in Australia
• Most managed in tertiary endocrine surgical centres
• Higher awareness and incidental detection on CT/MRI

Mortality

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Applied Basic Sciences

Catecholamine Biosynthesis Pathway

The Blaschko Pathway describes catecholamine synthesis from the amino acid L-tyrosine:[16,17]

TYROSINE
    │
    ▼ Tyrosine Hydroxylase (TH) ← RATE-LIMITING STEP
    │   - Cofactors: Tetrahydrobiopterin (BH₄), O₂, Fe²⁺
    │   - Location: Cytosol
    │   - Feedback inhibition by catecholamines
    │
L-DOPA (L-dihydroxyphenylalanine)
    │
    ▼ Aromatic L-amino Acid Decarboxylase (AADC)
    │   - Cofactor: Pyridoxal phosphate (Vitamin B₆)
    │   - Location: Cytosol
    │
DOPAMINE
    │
    ▼ Dopamine β-hydroxylase (DBH)
    │   - Cofactors: Ascorbate (Vitamin C), Cu²⁺
    │   - Location: Inside chromaffin granules/vesicles
    │
NORADRENALINE (Norepinephrine)
    │
    ▼ Phenylethanolamine N-methyltransferase (PNMT)
    │   - Cofactor: S-adenosylmethionine (SAMe)
    │   - Location: Cytosol (primarily adrenal medulla)
    │   - Induced by glucocorticoids from adrenal cortex
    │
ADRENALINE (Epinephrine)

Clinical Relevance:

• Tyrosine hydroxylase inhibition (metyrosine/α-methylparatyrosine) reduces catecholamine synthesis - used adjunctively in refractory cases[18]
• PNMT expression requires cortisol induction → extra-adrenal paragangliomas produce noradrenaline only (lack cortisol exposure)
• Hereditary syndromes have characteristic biochemical phenotypes:
  • "MEN2/RET: Adrenergic (elevated metanephrine from adrenaline)"
  • "VHL: Noradrenergic (elevated normetanephrine from noradrenaline only)"
  • "SDHB: Often dopaminergic or noradrenergic"

Catecholamine Storage and Release

Chromaffin cells store catecholamines in dense-core granules along with:

• Chromogranin A (useful tumour marker)[19]
• ATP
• Enkephalins and neuropeptides

Release mechanisms:

• Sympathetic nerve stimulation (acetylcholine → nicotinic receptors)
• Tumour-specific triggers: direct pressure, histamine, glucagon, metoclopramide, opioids, tyramine-rich foods

Adrenergic Receptor Pharmacology

Understanding receptor subtypes is essential for CICM examination:[20,21]

Why Alpha-Blockade MUST Precede Beta-Blockade

This is a CRITICAL exam concept and clinical safety principle:

1. Baseline State: High circulating catecholamines stimulate BOTH alpha and beta receptors:

   • α₁: Vasoconstriction → hypertension
   • β₂: Vasodilation (partial opposition to α₁ vasoconstriction)
   • β₁: Tachycardia, increased cardiac output

2. Beta-Blockade Alone (WITHOUT prior alpha-blockade):

   • Blocks β₂-mediated vasodilation
   • Blocks β₁-mediated cardiac output
   • UNOPPOSED α₁ vasoconstriction → paradoxical severe hypertensive crisis
   • Risk of stroke, MI, aortic dissection, death[22,23]

3. Alpha-Blockade First (CORRECT approach):

   • Blocks α₁ vasoconstriction → vasodilation → BP reduction
   • Causes reflex tachycardia (β₁-mediated compensatory response)
   • THEN add β₁-blocker to control reflex tachycardia

4. Labetalol Controversy:

   • Combined α and β-blocker (1:7 ratio α:β effect)
   • Beta-blocking effect predominates → may cause paradoxical hypertension
   • Generally NOT recommended as first-line[24]
   • Some centres use with extreme caution ONLY after adequate α-blockade established

Catecholamine Metabolism and Diagnostic Testing

Catecholamines are metabolized by two enzymes:[25,26]

1. Catechol-O-methyltransferase (COMT): Converts catecholamines to metanephrines

   • Noradrenaline → Normetanephrine
   • Adrenaline → Metanephrine

2. Monoamine oxidase (MAO): Further metabolism to VMA (vanillylmandelic acid)

Diagnostic Hierarchy:

Why Plasma Metanephrines Are Superior:

• Produced continuously within tumour cells (not dependent on episodic release)
• Less affected by patient stress, medications, or sampling conditions
• High negative predictive value (normal result essentially excludes diagnosis)

Hereditary Phaeochromocytoma Syndromes

Approximately 35-40% of phaeochromocytomas are hereditary:[28,29,30]

Clinical Implications:

• All patients with PPGL should be offered genetic testing (Endocrine Society 2014)[31]
• SDHB mutation carriers require lifelong surveillance (highest malignancy risk)
• Family screening essential for all hereditary syndromes
• Bilateral adrenalectomy may be indicated in MEN2/VHL (cortisol-sparing partial adrenalectomy preferred)

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Clinical Presentation

Classic Presentation: "The Triad"

Paroxysmal episodes (lasting 15-60 minutes) of:[32]

1. Headache (severe, throbbing, occipital)
2. Sweating (profuse diaphoresis)
3. Palpitations (with tachycardia)

Associated with:

• Severe hypertension (SBP 180-280 mmHg)
• Pallor (NOT flushing - vasoconstriction)
• Anxiety, sense of impending doom
• Tremor
• Nausea, vomiting
• Chest pain, abdominal pain
• Visual disturbances

Presentation Patterns

Triggers for Paroxysmal Crisis

• Physical: Exercise, abdominal palpation, Valsalva manoeuvre, micturition, defecation
• Pharmacological: Metoclopramide, glucagon, histamine, opioids, sympathomimetics, contrast media
• Anaesthetic: Induction agents, laryngoscopy, surgical manipulation of tumour
• Dietary: Tyramine-rich foods (cheese, wine, chocolate)
• Emotional stress

Phaeochromocytoma Crisis (Catecholamine Storm)

Definition: Life-threatening hyperadrenergic state with multi-organ dysfunction:[33,34]

Cardiovascular:

• Severe hypertension (SBP >200-300 mmHg)
• Hypertensive encephalopathy
• Acute pulmonary oedema
• Takotsubo-like cardiomyopathy
• Catecholamine-induced cardiomyopathy
• Arrhythmias (VT, VF, AF)
• Acute coronary syndrome/MI

Neurological:

• Hypertensive encephalopathy
• Intracerebral haemorrhage
• Subarachnoid haemorrhage
• Posterior reversible encephalopathy syndrome (PRES)
• Seizures

Other:

• Acute kidney injury
• Lactic acidosis (excess catecholamine effects)
• Hyperthermia
• Rhabdomyolysis
• Multiorgan failure

Differential Diagnosis

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Investigations

Biochemical Diagnosis

First-Line: Plasma Free Metanephrines[27,35]

Interpretation:

• Levels >2× upper limit of normal: 100% specificity for phaeochromocytoma
• Borderline elevation (1-2× ULN): May be false positive (medications, stress, renal failure)
• Age-adjusted reference ranges increasingly used

Second-Line: 24-Hour Urine Catecholamines and Metanephrines

False Positive Causes

Medications:

• Tricyclic antidepressants (interfere with assay)
• Levodopa
• Sympathomimetics (pseudoephedrine, phenylephrine)
• Monoamine oxidase inhibitors
• Buspirone, sotalol

Conditions:

• Acute stress (stroke, MI, sepsis, trauma)
• Obstructive sleep apnoea
• Renal failure (reduced clearance)
• Essential hypertension (mild elevations)

Localization Imaging

CT Abdomen with Contrast (First-Line):[36]

• Sensitivity: 85-98% for adrenal tumours
• Specificity: Lower due to incidentalomas
• Features: Well-circumscribed mass, >3 cm, heterogeneous enhancement, possible necrosis/haemorrhage
• Hounsfield units: >10 HU (lipid-poor adenomas typically less than 10 HU)

MRI Abdomen (Alternative/Preferred if contrast contraindicated):

• "Light bulb" sign: High T2 signal intensity
• Better for paragangliomas, metastatic workup
• Safe in pregnancy

Functional Imaging:[37,38]

Additional Investigations

Cardiac Assessment:

• ECG: LVH, ST-T changes, arrhythmias, QTc prolongation
• Troponin: May be elevated in catecholamine cardiomyopathy
• BNP/NT-proBNP: Elevated in cardiac dysfunction
• Echocardiography: Assess LV function, cardiomyopathy (systolic dysfunction, regional wall motion abnormalities, Takotsubo pattern)

Genetic Testing:[31]

• Recommended for ALL patients with PPGL
• Targeted panel: RET, VHL, SDHB, SDHD, SDHC, SDHA, SDHAF2, NF1, MAX, TMEM127
• Prioritize based on clinical features

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ICU Management

Acute Phaeochromocytoma Crisis

ABCDE Approach:

A - Airway:

• Assess patency, protect if GCS reduced
• Prepare for emergency intubation if encephalopathy/seizures
• RSI considerations: Avoid ketamine (sympathomimetic), prefer propofol or thiopentone

B - Breathing:

• High-flow oxygen if hypoxic
• Assess for pulmonary oedema (catecholamine-induced)
• NIV or mechanical ventilation if respiratory failure
• CXR to assess pulmonary oedema

C - Circulation - CRITICAL MANAGEMENT:

Immediate Actions:

1. Arterial line - Beat-to-beat BP monitoring essential
2. Central venous access - For vasoactive infusions
3. Cardiac monitoring - Continuous ECG, defibrillator ready

Pharmacological Management of Hypertensive Crisis:[39,40,41]

Target BP in Crisis:

• Initial: Reduce MAP by 20-25% in first hour (avoid precipitous drop → ischaemia)
• Target: SBP 140-160 mmHg initially, then gradually lower
• Avoid BP less than 90/60 (risk of end-organ hypoperfusion)

D - Disability:

• GCS assessment, pupils
• Seizure precautions
• CT brain if neurological deficits (exclude stroke, PRES)
• Glucose monitoring (hyperglycaemia common in crisis)

E - Exposure:

• Core temperature (hyperthermia)
• Evidence of end-organ damage
• Skin pallor (characteristic), diaphoresis

Pre-Operative Optimization Protocol

The 10-14 Day Protocol:[42,43,44]

Goals Before Surgery:

Step 1: Alpha-Blockade (Days 1-7)

Phenoxybenzamine (First-Line):[45]

• Mechanism: Irreversible, non-competitive α₁ and α₂ blocker
• Starting dose: 10 mg BD PO
• Titration: Increase by 10-20 mg every 2-3 days
• Typical final dose: 20-40 mg BD (up to 1-2 mg/kg/day)
• Side effects: Orthostatic hypotension, reflex tachycardia, nasal congestion, fatigue, sedation, retrograde ejaculation

Alternative Alpha-Blockers:

Phenoxybenzamine vs Selective α₁-Blockers:[46]

• Phenoxybenzamine: More complete blockade, longer duration (persists after stopping - advantage for intra-op), but more side effects, more post-op hypotension
• Doxazosin/Prazosin: Fewer side effects, shorter action, but less complete blockade, may require higher doses

Step 2: Beta-Blockade (Days 3-7, AFTER adequate α-blockade)

Indications:

• Resting tachycardia >100 bpm (reflex from α-blockade)
• Persistent tachyarrhythmias
• Adrenaline-secreting tumours (β₂-mediated vasodilation component)

Agents:

CRITICAL: Never start beta-blockers before adequate alpha-blockade is established (minimum 3-4 days of phenoxybenzamine with evidence of blockade)[47]

Step 3: Volume Expansion

• High-salt diet (10-12 g NaCl/day) starting with α-blockade
• Liberal fluid intake (2-3 L/day)
• IV crystalloid 1-2 L night before surgery
• Target: 2-3 kg weight gain, HCT decrease 5-10%
• Rationale: Chronic catecholamine excess causes vasoconstriction → reduced plasma volume → volume expansion prevents post-resection hypotension

Step 4: Additional Medications (Selected Cases)

Metyrosine (α-methylparatyrosine):[18]

• Mechanism: Inhibits tyrosine hydroxylase → reduces catecholamine synthesis
• Dose: 250 mg QID, increase to 1-4 g/day
• Indication: Refractory cases, malignant disease, inoperable tumours
• Side effects: Sedation, depression, diarrhoea, crystalluria
• Availability: Limited (not readily available in Australia)

Calcium Channel Blockers:

• Nicardipine, amlodipine
• Adjunctive for BP control
• Useful if intolerant of α-blockers

Intraoperative Management

Anaesthetic Considerations:[48,49,50]

Pre-Induction:

• Invasive monitoring in situ (arterial line, CVP)
• Vasoactive medications drawn up and ready:
  • Phentolamine (boluses prepared)
  • Nitroprusside infusion ready
  • Esmolol infusion ready
  • Magnesium sulphate
  • Noradrenaline infusion (for post-resection)

Induction:

• Avoid sympathomimetic agents (ketamine, pancuronium)
• Recommended: Propofol, fentanyl, rocuronium
• Prepare for hypertensive response to laryngoscopy (consider remifentanil infusion, lidocaine, deeper anaesthesia)

Maintenance:

• Volatile anaesthetics (sevoflurane, desflurane) - provide some myocardial protection
• Opioid-based technique to minimize catecholamine responses
• Avoid: Histamine-releasing drugs (morphine, atracurium), metoclopramide

Critical Events During Surgery:

1. Tumour Manipulation → Hypertensive Crisis:

• SBP may exceed 250-300 mmHg
• Immediate management:
  • Phentolamine 2-5 mg IV bolus (repeat every 1-2 min as needed)
  • Nitroprusside infusion 0.5-10 μg/kg/min
  • Magnesium sulphate 2-4 g IV
  • Nicardipine infusion
  • Esmolol for tachyarrhythmias (ONLY after α-blockade)
  • Surgeon to temporarily release tumour manipulation

2. Arrhythmias:

• Tachyarrhythmias: Esmolol, amiodarone, lidocaine
• Ventricular arrhythmias: Defibrillation if VT/VF, lidocaine, amiodarone
• Magnesium for QTc prolongation

3. Ligation of Adrenal Vein → Sudden Catecholamine Withdrawal:

• Abrupt BP drop (may be profound: SBP 50-60 mmHg)
• Management:
  • Stop vasodilators immediately
  • Aggressive crystalloid boluses (500-1000 mL rapidly)
  • Noradrenaline infusion (titrate to MAP >65)
  • Consider vasopressin if refractory

Post-Operative ICU Management

Immediate Post-Resection Care:[51,52]

1. Hypotension (Most Common Complication)

Pathophysiology:

• Abrupt cessation of catecholamine excess
• Down-regulated α-receptors (chronic exposure)
• Residual α-blockade (phenoxybenzamine persists 24-48h)
• Relative hypovolaemia (despite pre-operative volume loading)

Management:

• Aggressive IV fluids (crystalloid, aim CVP 10-14)
• Noradrenaline infusion (0.05-0.5 μg/kg/min)
• Consider vasopressin (0.01-0.04 U/min) if refractory
• Target MAP >65 mmHg
• Usually resolves within 24-48h as receptor sensitivity returns

2. Hypoglycaemia

Pathophysiology:

• Catecholamines inhibit insulin release (α₂ receptors on pancreatic β-cells)
• Removal → rebound hyperinsulinaemia → hypoglycaemia
• Catecholamines stimulate glycogenolysis → removal → reduced glucose release

Management:

• Monitor BSL hourly for first 24h, then 2-4 hourly for 48h
• 10% dextrose infusion if BSL less than 4 mmol/L
• Bolus 25-50 mL 50% dextrose for severe hypoglycaemia (less than 3 mmol/L)
• Avoid over-correction

3. Adrenal Insufficiency (Bilateral Adrenalectomy)

• If bilateral adrenalectomy: Immediate and lifelong hydrocortisone replacement
• Stress-dose hydrocortisone: 100 mg IV Q8H for 24-48h, then taper to maintenance
• Fludrocortisone: 100-200 μg daily (may not be needed immediately)
• MedicAlert bracelet, patient education

4. Catecholamine-Induced Cardiomyopathy

• May persist post-operatively
• Serial echocardiography
• Usually reversible over weeks to months
• Standard heart failure therapy if required (ACE-I, β-blockers once stable)

5. Persistent Hypertension

Causes to consider:

• Residual tumour
• Metastatic disease
• Co-existing essential hypertension
• Renovascular disease
• Pain, anxiety

ICU Monitoring:

• Continuous arterial BP monitoring
• CVP monitoring
• Hourly BSL for 24h
• 12-lead ECG daily
• Cardiac enzymes if concern for catecholamine cardiomyopathy
• UO, fluid balance

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Monitoring & Complications

ICU-Specific Monitoring

Complications

Early Complications (First 24-48 hours):

Late Complications:

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Prognosis & Outcome Measures

Mortality

Recurrence

• Benign disease: 5-15% recurrence rate over 10-20 years
• Malignant disease: Higher recurrence; requires aggressive surveillance
• Hereditary syndromes: Lifelong risk of new tumours (second adrenal, extra-adrenal, metachronous PGL)

Long-Term Surveillance

Endocrine Society Recommendations:[31]

• Annual plasma or urinary metanephrines for at least 10 years (lifelong recommended)
• Earlier/more frequent if:
  • Hereditary syndrome
  • Large tumour (>5 cm)
  • Paraganglioma (extra-adrenal)
  • Incomplete resection
  • Young age at diagnosis

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Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples

Epidemiology:

• Limited specific data on phaeochromocytoma incidence in Indigenous Australians
• Higher overall prevalence of secondary hypertension causes
• Delayed presentation due to healthcare access barriers
• Higher rates of diabetes and cardiovascular disease complicating management

Clinical Considerations:

• Hypertension is often attributed to more common causes (essential HTN, renovascular, diabetic nephropathy) - maintain index of suspicion for phaeochromocytoma in paroxysmal or resistant HTN
• Remote/rural location may delay diagnosis and access to tertiary surgical centres
• Pre-operative optimization may need to occur in regional centres with telemedicine support
• Retrieval to tertiary centre (Sydney, Melbourne, Brisbane, Perth, Adelaide) for surgery

Cultural Safety:

• Involve Aboriginal Hospital Liaison Officers (AHLOs) early
• Explain the condition and treatment plan in culturally appropriate terms
• Allow time for family discussions and decision-making
• Recognize importance of connection to Country - discuss timing of surgery with patient/family
• Involve family in care planning and bedside support
• Use interpreters if English is not first language
• Discharge planning: Ensure community/remote health services are informed and capable of ongoing surveillance

Genetic Testing Considerations:

• Genetic counselling must be culturally sensitive
• Family implications require careful discussion
• Community implications of hereditary syndromes
• Privacy and confidentiality especially important in small communities

Māori Health Considerations

Cultural Framework:

• Whānau-centred care: Involve extended family in decision-making
• Kaumātua involvement: Elder guidance may be sought for significant medical decisions
• Tikanga: Respect cultural protocols around treatment and the body
• Manaakitanga: Demonstrate hospitality and respect

Practical Considerations:

• Māori Health Workers can facilitate communication
• Allow additional time for whānau consultation before major decisions
• Consider cultural and spiritual support services
• Explain genetic implications in context of whānau/iwi connections
• Post-discharge follow-up may require coordination with Māori health providers

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Progressive Difficulty Assessments

Basic Level

Question 1: Catecholamine Synthesis

Q: Name the enzymes involved in catecholamine synthesis from tyrosine to adrenaline, and identify the rate-limiting step.

A:

1. Tyrosine hydroxylase (TH) - converts tyrosine to L-DOPA - RATE-LIMITING STEP
2. Aromatic L-amino acid decarboxylase (AADC) - converts L-DOPA to dopamine
3. Dopamine β-hydroxylase (DBH) - converts dopamine to noradrenaline
4. Phenylethanolamine N-methyltransferase (PNMT) - converts noradrenaline to adrenaline

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Question 2: Alpha vs Beta Blockade

Q: Explain why beta-blockers must NOT be given before alpha-blockers in phaeochromocytoma.

A:

• Beta-2 receptors cause vasodilation in skeletal muscle vasculature
• Alpha-1 receptors cause vasoconstriction
• In phaeochromocytoma, high catecholamines stimulate both receptors
• Beta-2 vasodilation partially opposes alpha-1 vasoconstriction
• If beta-blockers are given first, beta-2 vasodilation is blocked
• This leaves unopposed alpha-1 vasoconstriction
• Result: Paradoxical severe hypertensive crisis, risking stroke, MI, or death

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Question 3: Classic Triad

Q: What is the classic triad of phaeochromocytoma presentation?

A:

1. Headache (severe, throbbing)
2. Sweating (profuse diaphoresis)
3. Palpitations

Associated with paroxysmal or sustained severe hypertension.

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Intermediate Level

Question 1: Pre-operative Optimization

Q: A 45-year-old woman with phaeochromocytoma is scheduled for laparoscopic adrenalectomy. She presents with BP 190/110 mmHg and HR 95 bpm. Outline the pre-operative optimization protocol.

A:

Goals (over 10-14 days):

• BP less than 130/80 sitting, orthostatic drop less than 20/10 mmHg
• HR 60-80 bpm seated
• Volume expansion (2-3 kg weight gain)
• No new ECG changes, no symptoms of catecholamine excess

Step 1: Alpha-Blockade (Days 1-7):

• Phenoxybenzamine 10 mg BD, increase every 2-3 days to 20-40 mg BD
• Alternative: Doxazosin 2-16 mg daily
• Monitor for orthostatic hypotension, nasal congestion, reflex tachycardia

Step 2: Volume Expansion:

• High-salt diet (10-12 g/day)
• Liberal fluids (2-3 L/day)
• IV crystalloid 1-2 L night before surgery

Step 3: Beta-Blockade (Days 3-7, AFTER adequate α-blockade):

• Propranolol 20-40 mg TDS or atenolol 25-100 mg daily
• ONLY if persistent tachycardia >100 bpm

Step 4: Consider additional agents:

• Calcium channel blockers for refractory hypertension
• Metyrosine (if available) for high-catecholamine tumours

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Question 2: Intraoperative Hypertensive Crisis

Q: During laparoscopic adrenalectomy, the surgeon manipulates the tumour and BP rises to 270/150 mmHg with HR 130 bpm. Describe your management.

A:

Immediate Actions:

1. Alert surgical team - request temporary release of tumour manipulation
2. Confirm arterial line is functional and accurate
3. Ensure adequate anaesthetic depth (increase volatile, add fentanyl/remifentanil)

Pharmacological Management:

1. Phentolamine 2-5 mg IV bolus - can repeat every 1-2 minutes
2. Sodium nitroprusside infusion 0.5-10 μg/kg/min - titratable
3. Magnesium sulphate 2-4 g IV bolus (reduces catecholamine release, anti-arrhythmic)
4. Nicardipine infusion 5-15 mg/h as alternative/adjunct

For Tachycardia (ONLY after BP controlled):

• Esmolol 50-200 μg/kg/min - short-acting, titratable

Monitoring:

• Continuous arterial BP
• Continuous ECG for arrhythmias
• 12-lead ECG for ischaemia
• ABG for acidosis

Target: Reduce MAP by 20-25% initially, then SBP 140-160 mmHg

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Exam Level

Question 1: Post-Resection Hypotension

Stem: A 52-year-old male undergoes successful laparoscopic left adrenalectomy for a 6 cm phaeochromocytoma. Intraoperatively, he had multiple hypertensive episodes managed with phentolamine. Immediately after ligation of the adrenal vein, his BP drops to 65/40 mmHg with HR 75 bpm.

Q1: Explain the pathophysiology of this hypotension. (5 marks)

Q2: Describe your immediate management. (8 marks)

Q3: List complications to monitor for in the first 24 hours and your surveillance strategy. (7 marks)

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SAQ Practice

SAQ 1: Catecholamine Physiology and Receptor Pharmacology

Time Allocation: 10 minutes Total Marks: 20

Stem: A 38-year-old woman presents to the Emergency Department with severe headache, palpitations, and profuse sweating. Her blood pressure is 240/140 mmHg with heart rate 125 bpm.

Question 1.1 (8 marks)

Outline the catecholamine biosynthesis pathway from tyrosine to adrenaline, identifying the rate-limiting step and the location of each enzymatic reaction.

Question 1.2 (6 marks)

Compare the effects of alpha-1, beta-1, and beta-2 adrenergic receptor stimulation.

Question 1.3 (6 marks)

Explain why alpha-adrenergic blockade must precede beta-adrenergic blockade in phaeochromocytoma management.

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Model Answer - SAQ 1

Question 1.1 (8 marks)

Catecholamine Biosynthesis Pathway:

Rate-Limiting Step: Tyrosine hydroxylase (Step 1) - controlled by:

• Feedback inhibition by catecholamines
• Phosphorylation by protein kinases (activated by sympathetic stimulation)
• Cofactor availability (tetrahydrobiopterin, O₂, Fe²⁺)

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Question 1.2 (6 marks)

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Question 1.3 (6 marks)

Explanation (structured response):

Normal State in Phaeochromocytoma (1 mark):

• Excess catecholamines stimulate both alpha and beta receptors
• Alpha-1: Vasoconstriction → hypertension
• Beta-2: Vasodilation (partial counter-regulation)
• Net effect: Hypertension with some attenuation by beta-2

Effect of Beta-Blockade Alone (2 marks):

• Blocks beta-2 vasodilation → removes counter-regulation
• Blocks beta-1 cardiac output → reduced CO
• Unopposed alpha-1 vasoconstriction → severe hypertension
• Risk: Hypertensive crisis, stroke, MI, aortic dissection, death

Correct Sequence (2 marks):

• Alpha-blockade FIRST → blocks vasoconstriction → BP decreases
• This causes reflex tachycardia (baroreceptor-mediated)
• Beta-blockade SECOND → controls reflex tachycardia safely

Clinical Application (1 mark):

• Phenoxybenzamine for 3-7 days before adding propranolol/atenolol
• Never give isolated beta-blockade (including labetalol with caution)

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SAQ 2: Pre-operative Optimization and Intraoperative Management

Time Allocation: 10 minutes Total Marks: 20

Stem: A 47-year-old man is diagnosed with a 5 cm right adrenal phaeochromocytoma after investigation of paroxysmal hypertension. Plasma normetanephrine is 8× the upper limit of normal. He is scheduled for laparoscopic right adrenalectomy in 3 weeks.

Question 2.1 (8 marks)

Describe your pre-operative optimization protocol, including specific agents, doses, duration, and targets.

Question 2.2 (6 marks)

During tumour manipulation, his blood pressure rises to 280/160 mmHg. Outline your immediate pharmacological management.

Question 2.3 (6 marks)

Immediately after ligation of the adrenal vein, his blood pressure drops to 55/35 mmHg. Explain the pathophysiology and describe your management.

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Model Answer - SAQ 2

Question 2.1 (8 marks)

Pre-operative Optimization Protocol (10-14 days):

Goals (2 marks):

• BP less than 130/80 mmHg seated, orthostatic drop less than 20/10 mmHg
• HR 60-80 bpm seated
• No ST-T changes on ECG
• Volume expansion (2-3 kg weight gain)

Step 1: Alpha-Blockade - Days 1-7 (3 marks):

• Phenoxybenzamine 10 mg PO BD
• Increase by 10-20 mg every 2-3 days
• Target: 20-40 mg BD (up to 1-2 mg/kg/day)
• Side effects: Orthostatic hypotension (desired), reflex tachycardia, nasal congestion
• Alternative: Doxazosin 2-16 mg daily, Prazosin 2-5 mg TDS

Step 2: Volume Expansion (1 mark):

• High-salt diet (10-12 g NaCl/day)
• Liberal oral fluids (2-3 L/day)
• IV crystalloid 1-2 L night before surgery

Step 3: Beta-Blockade - Days 3-7 AFTER adequate alpha-blockade (2 marks):

• ONLY if tachycardia >100 bpm or arrhythmias
• Propranolol 20-40 mg TDS or Atenolol 25-100 mg daily
• NEVER before adequate alpha-blockade established

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Question 2.2 (6 marks)

Immediate Management of Intraoperative Hypertensive Crisis:

Immediate Actions (1 mark):

• Alert surgeon to pause tumour manipulation
• Confirm arterial line accuracy

Pharmacological Management (4 marks):

Target (1 mark):

• Reduce MAP by 20-25% initially
• Target SBP 140-160 mmHg

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Question 2.3 (6 marks)

Pathophysiology of Post-Resection Hypotension (3 marks):

1. Abrupt catecholamine withdrawal - ligation of adrenal vein stops catecholamine secretion
2. Down-regulated adrenergic receptors - chronic catecholamine exposure causes receptor desensitization
3. Residual alpha-blockade - phenoxybenzamine is irreversible, persists 24-48h
4. Relative hypovolaemia - despite pre-op volume loading, patients remain volume-depleted
5. Loss of catecholamine-mediated vasoconstriction - sudden vasodilation

Immediate Management (3 marks):

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Hot Case Scenarios

Hot Case 1: Pre-operative Phaeochromocytoma Optimization

Setting: ICU Bed 4 Duration: 20 minutes (10 min assessment + 10 min discussion) Equipment: Monitors, arterial line, peripheral cannula, charts

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Actor/Simulator Briefing (Not given to candidate):

Patient Details:

• Age: 42 years
• Gender: Female
• Diagnosis: Phaeochromocytoma - Day 8 of pre-operative alpha-blockade
• Day of ICU stay: Day 2 (admitted for BP optimization)

History:

• 4 cm right adrenal phaeochromocytoma, diagnosed after paroxysmal hypertension workup
• Plasma normetanephrine 6× ULN, plasma metanephrine 4× ULN
• Started phenoxybenzamine 8 days ago, now on 30 mg BD
• Admitted to ICU 2 days ago after BP 195/120 at home despite oral blockade
• Surgery planned in 5 days
• PMHx: Type 2 diabetes, anxiety
• No family history of endocrine tumours

Examination Findings:

• Alert, comfortable at rest
• BP 135/85 sitting, 115/75 standing (orthostatic drop)
• HR 95 bpm, regular
• Nasal congestion (phenoxybenzamine side effect)
• No respiratory distress
• Abdomen soft, no masses palpable
• No focal neurology

Current Management:

• Phenoxybenzamine 30 mg PO BD
• IV 0.9% NaCl at 100 mL/h
• High-salt diet (10 g/day)
• Metformin 1 g BD
• Lorazepam 0.5 mg PRN

Charts:

• BP trending down from 180/110 on admission to 135/85 today
• Orthostatic drop now present (indicates adequate blockade)
• HR 90-100 (reflex tachycardia)
• BSL 6-10 mmol/L
• Weight: +2 kg since starting treatment

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Expected Performance:

History (3 marks):

• Duration of alpha-blockade, current dose
• Side effects (orthostatic symptoms, nasal congestion)
• Symptom control (headaches, palpitations, sweating resolved?)
• Dietary salt intake, fluid intake
• Any paroxysmal episodes since admission

Examination (10 marks):

• Lying/standing BP (assess orthostatic response)
• HR (reflex tachycardia indicates blockade)
• Phenoxybenzamine side effects (nasal congestion, postural symptoms)
• Cardiac examination (S3, murmurs - catecholamine cardiomyopathy)
• Signs of volume expansion (JVP, peripheral oedema)

One-Minute Summary (2 marks): "This is a 42-year-old woman, Day 8 of phenoxybenzamine for pre-operative optimization of a right adrenal phaeochromocytoma. She is currently on phenoxybenzamine 30 mg BD with good BP control of 135/85 and appropriate orthostatic drop. She has reflex tachycardia at 95 bpm. Key issues are: 1) Need to add beta-blockade for tachycardia; 2) Confirm adequacy of volume loading. Plan is to add atenolol, continue volume expansion, and proceed to surgery in 5 days if targets met."

Discussion Points:

1. Criteria for adequate pre-operative optimization
2. When to add beta-blocker and which agent
3. Role of metyrosine
4. Intraoperative management plan
5. Communication with patient and anaesthetic team

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Hot Case 2: Post-Resection Hypotension and Hypoglycaemia

Setting: ICU Bed 7 Duration: 20 minutes (10 min assessment + 10 min discussion) Equipment: Ventilator, arterial line, CVC, vasoactive infusions, IDC

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Actor/Simulator Briefing:

Patient Details:

• Age: 55 years
• Gender: Male
• Diagnosis: Post laparoscopic right adrenalectomy for phaeochromocytoma
• Time post-op: 4 hours

History:

• 7 cm right adrenal phaeochromocytoma
• Pre-operative phenoxybenzamine × 12 days, propranolol added Day 7
• Intraoperative: Multiple hypertensive crises managed with phentolamine
• Adrenal vein ligated 4 hours ago → immediate hypotension
• Required aggressive fluid resuscitation and noradrenaline intraoperatively
• BSL was 3.2 mmol/L 1 hour ago, treated with 10% dextrose

Examination Findings:

• Intubated, sedated, RASS -2
• BP 95/60 (on noradrenaline 0.15 μg/kg/min)
• HR 75 bpm, sinus rhythm
• CVP 12 mmHg
• Warm peripheries, CRT 2s
• Ventilator: SIMV, Vt 500, RR 12, PEEP 5, FiO2 0.3
• Abdomen: Soft, 3 laparoscopic port dressings, no distension
• UO: 40 mL/h (0.5 mL/kg/h)

Current Management:

• Noradrenaline 0.15 μg/kg/min
• 10% dextrose at 50 mL/h
• Propofol 20 mg/h, fentanyl 30 μg/h
• Hartmann's at 125 mL/h
• Pantoprazole 40 mg IV

Charts:

• Cumulative fluid balance: +3.5 L since surgery
• BSL: 8.2 mmol/L (was 3.2, now on dextrose infusion)
• Lactate: 1.5 mmol/L
• Hb: 105 g/L
• Recent ABG: pH 7.38, PaCO2 42, PaO2 120, HCO3 24

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Expected Performance:

Assessment Phase (15 marks):

• Recognize post-resection hypotension on vasopressors
• Note adequate volume resuscitation (CVP 12, +3.5 L)
• Check BSL - hypoglycaemia risk identified and being managed
• Review surgical site - exclude haemorrhage
• Assess adequacy of sedation for extubation planning

Discussion Phase (15 marks):

1. Pathophysiology of post-resection hypotension
2. Vasopressor weaning strategy
3. BSL monitoring frequency and targets
4. Extubation criteria
5. Complications to monitor for

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Viva Scenarios

Viva 1: Acute Phaeochromocytoma Crisis - Undiagnosed

Stem: "A 45-year-old man presents to the Emergency Department with sudden severe headache, palpitations, and diaphoresis. BP is 260/150 mmHg, HR 140 bpm. He has no significant past medical history. You are called as the ICU registrar."

Duration: 12 minutes

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Opening Question:

Examiner: "What is your differential diagnosis and immediate management?"

Expected Answer:

Differential Diagnosis (CRITICAL to include phaeochromocytoma):

• Phaeochromocytoma crisis
• Hypertensive emergency (essential HTN with end-organ damage)
• Intracranial pathology (SAH, stroke, PRES)
• Cocaine/amphetamine toxicity
• Thyroid storm
• Panic attack with severe anxiety (diagnosis of exclusion)

Immediate Management (ABCDE approach):

• A: Patent, protect if GCS deteriorates
• B: Oxygen if hypoxic, prepare for intubation if pulmonary oedema
• C:
  • Arterial line (beat-to-beat monitoring essential)
  • "Antihypertensive: Given high suspicion of phaeochromocytoma, use phentolamine 2-5 mg IV or nitroprusside 0.5-10 μg/kg/min"
  • AVOID beta-blockers and labetalol until phaeochromocytoma excluded
• D: GCS, pupils, CT brain if neurological deficits
• E: Core temperature, ECG

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Follow-up Question 1:

Examiner: "Blood tests return. Plasma metanephrine is 15× upper limit of normal. How does this change your management?"

Expected Answer:

Confirms phaeochromocytoma - very high metanephrines are diagnostic:

• Continue phentolamine infusion for BP control
• Add nitroprusside or nicardipine if needed
• Do NOT use beta-blockers yet - need alpha-blockade first
• Magnesium sulphate 2-4 g IV (reduces catecholamine release, anti-arrhythmic)

Investigation:

• CT abdomen with contrast to localize tumour
• ECG, troponin, BNP (assess catecholamine cardiomyopathy)
• Echocardiography

Planning:

• ICU admission for monitoring and stabilization
• Once stable, commence oral phenoxybenzamine
• Multidisciplinary planning: Endocrinology, Endocrine Surgery, Anaesthesia, ICU

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Follow-up Question 2:

Examiner: "Despite phentolamine and nitroprusside, BP remains 200/120 and HR is 150. What now?"

Expected Answer:

Refractory Hypertension Management:

1. Optimize current therapy:

   • Increase nitroprusside (caution: cyanide toxicity with prolonged use)
   • Increase phentolamine infusion rate (1-5 mg/hour)

2. Add magnesium sulphate 2-4 g IV bolus, then 1-2 g/h infusion

3. Consider nicardipine 5-15 mg/h (calcium channel blocker)

4. For tachycardia (now that adequate α-blockade established):

   • Esmolol 50-200 μg/kg/min (short-acting, titratable)
   • Will control HR and reduce myocardial oxygen demand

5. If truly refractory (rare):

   • Metyrosine (if available) - inhibits catecholamine synthesis
   • Emergency surgery may be required (high mortality but sometimes necessary)

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Follow-up Question 3:

Examiner: "The patient stabilizes. What is your approach to definitive management?"

Expected Answer:

Definitive Management Plan:

1. Localization: CT/MRI abdomen (already done); consider ¹²³I-MIBG or ⁶⁸Ga-DOTATATE PET if uncertain or metastatic disease suspected

2. Pre-operative Optimization (10-14 days):

   • Transition to oral phenoxybenzamine 10 mg BD, titrate to 20-40 mg BD
   • Volume expansion (high-salt diet, IV fluids)
   • Add beta-blocker once alpha-blockade adequate
   • Target: BP less than 130/80, orthostatic drop, HR 60-80

3. Surgery:

   • Laparoscopic adrenalectomy by experienced endocrine surgeon
   • ICU post-operative monitoring

4. Genetic Testing:

   • Recommend for all patients with PPGL
   • If positive, family screening indicated

5. Long-term Surveillance:

   • Annual plasma metanephrines for at least 10 years

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Viva 2: Genetics and Hereditary Syndromes

Stem: "A 28-year-old woman is diagnosed with a left extra-adrenal paraganglioma. Plasma normetanephrine is elevated. You are asked to discuss the genetic implications."

Duration: 12 minutes

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Opening Question:

Examiner: "What is the likelihood that this patient has a hereditary syndrome, and which syndromes should you consider?"

Expected Answer:

Hereditary Likelihood:

• Approximately 35-40% of all PPGLs are hereditary
• Extra-adrenal location increases hereditary likelihood
• Young age (28 years) also increases hereditary likelihood
• This patient has high probability of hereditary syndrome

Syndromes to Consider:

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Follow-up Question 1:

Examiner: "Genetic testing reveals an SDHB mutation. What are the implications for this patient?"

Expected Answer:

SDHB Mutation Implications:

For This Patient:

1. High malignancy risk: 30-70% of SDHB-related PPGLs are malignant
2. Metastatic workup: ¹⁸F-FDG PET/CT or ⁶⁸Ga-DOTATATE PET to assess for metastatic disease
3. Aggressive surgical approach: Complete resection with clear margins essential
4. Lifelong surveillance: Annual biochemical (metanephrines) and imaging (MRI abdomen/pelvis, consider whole-body imaging)
5. Risk of additional tumours: May develop contralateral PGL, head/neck PGL, renal cell carcinoma, GIST

Genetic Counselling:

• Autosomal dominant inheritance
• 50% chance of passing mutation to offspring
• Recommend genetic counselling and testing for first-degree relatives
• Surveillance protocol for mutation carriers

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Follow-up Question 2:

Examiner: "How would management differ if she had MEN2A instead?"

Expected Answer:

MEN2A (RET Mutation) Differences:

MEN2A Management:

• Thyroid ultrasound + calcitonin (rule out MTC)
• Calcium/PTH (hyperparathyroidism)
• If bilateral phaeochromocytoma: Cortical-sparing surgery to avoid lifelong steroid dependence
• Prophylactic thyroidectomy based on specific RET mutation codon

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Viva 3: Intraoperative Management and Complications

Stem: "You are called to theatre. A 50-year-old man is undergoing laparoscopic adrenalectomy for phaeochromocytoma. His BP has risen to 290/170 mmHg with tumour manipulation."

Duration: 12 minutes

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Opening Question:

Examiner: "What is your immediate management?"

Expected Answer:

Immediate Actions:

1. Alert surgeon - request temporary cessation of tumour manipulation
2. Confirm arterial line is accurate
3. Ensure adequate anaesthetic depth

Pharmacological Management (systematic approach):

For Tachycardia/Arrhythmias (ONLY after BP controlled):

• Esmolol 50-200 μg/kg/min

Target: Reduce MAP by 20-25% initially

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Follow-up Question 1:

Examiner: "The adrenal vein is ligated and BP immediately drops to 50/30 mmHg. What has happened and how do you manage it?"

Expected Answer:

Pathophysiology:

• Abrupt catecholamine withdrawal (adrenal vein ligated = source removed)
• Down-regulated α-receptors (chronic exposure)
• Residual phenoxybenzamine effect (irreversible, persists 24-48h)
• Relative hypovolaemia
• Loss of catecholamine-mediated vasoconstriction

Management:

1. Stop all vasodilators immediately (nitroprusside, phentolamine)
2. Rapid fluid boluses: Crystalloid 500-1000 mL, repeat
3. Start noradrenaline: 0.1-0.5 μg/kg/min, titrate to MAP >65
4. Consider vasopressin: 0.01-0.04 U/min if refractory
5. Avoid blood pressure overshoot - receptors are sensitized over time

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Follow-up Question 2:

Examiner: "Two hours post-operatively, the BSL is 2.8 mmol/L. Why has this occurred and how do you manage it?"

Expected Answer:

Pathophysiology of Hypoglycaemia:

• Catecholamines normally inhibit insulin release (via α₂ receptors on pancreatic β-cells)
• Catecholamines stimulate glycogenolysis and gluconeogenesis
• Tumour removal → abrupt catecholamine withdrawal
• Rebound hyperinsulinaemia (no longer suppressed)
• Reduced glycogenolysis (no catecholamine stimulation)
• Result: Hypoglycaemia

Management:

1. Immediate: 25-50 mL of 50% dextrose IV
2. Maintenance: 10% dextrose infusion at 50-100 mL/h
3. Monitoring: BSL hourly for 24 hours, then 2-4 hourly
4. Target: BSL 6-10 mmol/L
5. Duration: Usually resolves within 24-48 hours

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Viva 4: Communication - Pre-operative Discussion

Stem: "You are the ICU consultant. A 40-year-old woman with phaeochromocytoma is scheduled for adrenalectomy. She asks to speak with you about the ICU aspects of her care."

Duration: 12 minutes

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Opening Question:

Examiner: "How would you structure this conversation?"

Expected Answer:

Structure (using SPIKES framework adapted):

1. Setting: Private room, adequate time, family present if patient wishes

2. Perception: "What have you been told about your surgery and the ICU stay?"

3. Information:

   • Explain the condition and why surgery is needed
   • Outline the perioperative plan:
     • 10-14 days of medication (alpha-blockade) to prepare
     • Surgery under general anaesthesia
     • ICU admission post-operatively (routine for this surgery)
   • Expected ICU stay: Usually 24-48 hours

4. Risks:

   • Intraoperative BP fluctuations (managed by anaesthetist with medications)
   • Post-operative low BP (may need medications/fluids to support)
   • Low blood sugar (monitored closely)
   • Rare: Heart complications, bleeding

5. Knowledge/Questions: "What questions do you have?"

6. Summary and Plan: Summarize, provide written information, offer follow-up

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Follow-up Question 1:

Examiner: "She asks: 'What are the chances something will go wrong?'"

Expected Answer:

Honest, Balanced Response:

"With modern techniques and good preparation, this surgery is very safe:

• Serious complications are rare - less than 2-3% in experienced centres
• The 10-14 days of medication you're taking makes the surgery much safer
• During surgery, your anaesthetist will have medications ready to manage any blood pressure changes
• After surgery, the main issue is usually low blood pressure - this is expected and we treat it with fluids and medications
• Most patients are in ICU for 1-2 days and home within a week

The key thing is that we know what to expect and we're well-prepared for it. This is a planned operation in a centre that does many of these."

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Follow-up Question 2:

Examiner: "She mentions she is Aboriginal. Are there specific considerations?"

Expected Answer:

Aboriginal-Specific Considerations:

1. Cultural Safety:

   • Ask: "Is there anything about your culture or beliefs that we should know about to care for you well?"
   • Offer Aboriginal Hospital Liaison Officer (AHLO) involvement
   • Allow time for family discussions

2. Family Involvement:

   • "Would you like family members to be part of our discussions?"
   • Recognize extended family may be important in decision-making
   • Accommodate larger family groups if possible

3. Communication:

   • Clear, jargon-free explanations
   • Written information at appropriate literacy level
   • Offer interpreter if English is not first language

4. Practical Considerations:

   • Connection to Country - if from remote community, timing of surgery may be important
   • Support for family who may need to travel
   • Discharge planning with community/remote health services

5. Genetic Counselling:

   • If genetic testing reveals hereditary syndrome, family implications require sensitive discussion
   • Community implications in small communities

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Viva 5: Evidence Base and Controversies

Stem: "Discuss the evidence base for pre-operative alpha-blockade in phaeochromocytoma."

Duration: 12 minutes

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Opening Question:

Examiner: "Is there RCT evidence for alpha-blockade before phaeochromocytoma surgery?"

Expected Answer:

Evidence Base:

Randomized Controlled Trials:

• No large RCTs comparing alpha-blockade vs no alpha-blockade
• Ethical concerns: Historical experience before alpha-blockade showed very high mortality (40-60%)
• Introduction of alpha-blockade (1960s-70s) dramatically reduced perioperative mortality

Observational Evidence:

• Cohort studies consistently show improved outcomes with pre-operative optimization
• Before alpha-blockade era: 40-60% perioperative mortality
• After alpha-blockade protocols: less than 2-3% perioperative mortality

Key Studies:

• Prys-Roberts 1976 (PMID: 1084927): Historical series showing benefit of combined α and β blockade
• Weingarten 2010 (PMID: 20181000): Mayo Clinic series - 293 patients, perioperative mortality under 1%
• Brunaud 2014 (PMID: 24389920): French series - 225 patients, compared phenoxybenzamine vs doxazosin

Consensus Guidelines:

• Endocrine Society 2014: Recommends pre-operative alpha-blockade (Grade 1, low quality evidence)
• Strong consensus despite limited high-quality evidence

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Follow-up Question 1:

Examiner: "Is there evidence comparing phenoxybenzamine to selective alpha-blockers?"

Expected Answer:

Phenoxybenzamine vs Selective α-Blockers (Doxazosin, Prazosin):

Comparative Studies:

• Prys-Roberts 2002 (PMID: 11940414): Non-randomized comparison; both effective
• Kocak 2002 (PMID: 12454685): Compared phenoxybenzamine vs doxazosin; similar intraoperative hemodynamic stability
• Brunaud 2014 (PMID: 24389920): 225 patients; no difference in outcomes between agents

Phenoxybenzamine Advantages:

• Irreversible blockade - complete, non-competitive
• Long duration - persists through surgery
• More "complete" blockade

Selective α-Blocker Advantages:

• Fewer side effects (less orthostatic hypotension, nasal congestion)
• Shorter half-life - less post-operative hypotension
• More readily available and cheaper
• Better tolerated

Meta-Analysis (Pacak 2007, PMID: 17405829):

• Insufficient evidence to recommend one agent over another
• "Effective blockade is more important than the specific agent used"

Current Practice:

• Both approaches used successfully
• Choice often depends on local preference and availability
• Key is to achieve adequate blockade rather than specific agent

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Follow-up Question 2:

Examiner: "A surgical colleague suggests operating without alpha-blockade in a patient with minimal symptoms. What is your response?"

Expected Answer:

Response to Proposed Surgery Without Alpha-Blockade:

Not Recommended - Clear professional disagreement:

1. Historical Evidence:

   • Pre-alpha-blockade era mortality 40-60%
   • Modern mortality with preparation less than 2-3%

2. Unpredictable Catecholamine Release:

   • Tumour manipulation causes massive catecholamine surge
   • Even "asymptomatic" tumours can release huge amounts
   • BP >300 mmHg, malignant arrhythmias, stroke, MI, death

3. Current Guidelines:

   • Endocrine Society 2014: Pre-operative alpha-blockade recommended for ALL patients
   • Endocrine Surgical Society: Supports pre-operative preparation
   • No current guideline supports "no blockade" approach

4. Risk-Benefit:

   • Alpha-blockade is safe, well-tolerated
   • Delay of 10-14 days is minimal compared to surgical risk reduction

5. Professional Response:

   • Discuss concerns with surgical colleague
   • Involve multidisciplinary team (endocrinology, anaesthesia, ICU)
   • Document concerns clearly
   • Escalate if patient safety at risk

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Viva 6: Ethical Considerations - Pregnancy

Stem: "A 32-year-old woman at 18 weeks gestation is diagnosed with phaeochromocytoma after presenting with hypertensive crisis. Discuss the management considerations."

Duration: 12 minutes

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Opening Question:

Examiner: "What are the unique considerations in managing phaeochromocytoma in pregnancy?"

Expected Answer:

Maternal-Fetal Considerations:

Risks:

• Untreated phaeochromocytoma in pregnancy: 40-50% maternal/fetal mortality[15]
• Hypertensive crisis can cause placental abruption, fetal demise
• Often misdiagnosed as pre-eclampsia

Diagnostic Considerations:

• Plasma metanephrines safe in pregnancy
• MRI preferred for localization (no radiation)
• Avoid ¹²³I-MIBG (radioactive)

Medical Management:

• Alpha-blockade: Phenoxybenzamine crosses placenta but used safely; alternatives include doxazosin
• Beta-blockade: Labelled use; propranolol, metoprolol used (avoid atenolol - IUGR)
• Magnesium sulphate: Safe, familiar in obstetrics
• Avoid: Metyrosine (teratogenic), nitroprusside (cyanide crosses placenta)

Timing of Surgery:

• Second trimester (18-24 weeks): Optimal time for surgery
  • Organogenesis complete (reduced teratogenic risk)
  • Uterus not too large (laparoscopic approach possible)
  • Lower risk of preterm labour than third trimester
• Third trimester: Higher anaesthetic/surgical risk; may consider delivery then adrenalectomy

Multidisciplinary Team:

• Obstetrics (high-risk), Endocrine Surgery, Anaesthesia, ICU, Endocrinology, Neonatology

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Follow-up Question:

Examiner: "She wants to delay surgery until after delivery. How do you counsel her?"

Expected Answer:

Counselling Approach:

Acknowledge her concerns:

• "I understand you want to protect your baby from surgery risks"
• "Let me explain the risks of both approaches so you can make an informed decision"

Present the Evidence:

Recommendation:

• "Based on the evidence, surgery in the second trimester is generally recommended"
• "Medical management alone carries significant ongoing risk"
• "However, this is your decision and we will support whatever you choose"

If She Chooses to Defer:

• Intensive medical management with alpha/beta-blockade
• Close BP monitoring
• Avoid triggers (stress, straining)
• Delivery planning: Avoid labour (catecholamine surge); Planned caesarean section under regional anaesthesia if possible
• Combined caesarean + adrenalectomy if needed

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References

Guidelines

1. Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942. PMID: 24893135

2. Neumann HPH, Young WF Jr, Eng C. Pheochromocytoma and Paraganglioma. N Engl J Med. 2019;381(6):552-565. PMID: 31390501

Catecholamine Synthesis and Receptor Pharmacology

3. Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004;56(3):331-349. PMID: 15181230

4. Dunkley PR, Bobrovskaya L, Graham ME, et al. Tyrosine hydroxylase phosphorylation: regulation and consequences. J Neurochem. 2004;91(5):1025-1043. PMID: 15569247

5. Hieble JP, Bylund DB, Clarke DE, et al. International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol Rev. 1995;47(2):267-270. PMID: 7568329

6. Bylund DB. Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992;6(3):832-839. PMID: 1346768

Diagnosis

7. Lenders JW, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002;287(11):1427-1434. PMID: 11903030

8. Eisenhofer G, Goldstein DS, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab. 2003;88(6):2656-2666. PMID: 12788870

9. Grouzmann E, Lamine F. Determination of catecholamines in plasma and urine. Best Pract Res Clin Endocrinol Metab. 2013;27(5):713-723. PMID: 24094641

10. Rao D, Peitzsch M, Prejbisz A, et al. Plasma methoxytyramine: clinical utility with metanephrines for diagnosis of pheochromocytoma and paraganglioma. Eur J Endocrinol. 2017;177(2):103-113. PMID: 28468939

Genetics

11. Dahia PL. Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer. 2014;14(2):108-119. PMID: 24442145

12. Favier J, Amar L, Gimenez-Roqueplo AP. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol. 2015;11(2):101-111. PMID: 25385035

13. Fishbein L, Leshchiner I, Walter V, et al. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell. 2017;31(2):181-193. PMID: 28162975

14. Buffet A, Venisse A, Nau V, et al. A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma. Horm Metab Res. 2012;44(5):359-366. PMID: 22517557

15. Amar L, Bertherat J, Baudin E, et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol. 2005;23(34):8812-8818. PMID: 16314641

Pre-operative Management

16. Prys-Roberts C. Phaeochromocytoma--recent progress in its management. Br J Anaesth. 2000;85(1):44-57. PMID: 10927994

17. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007;92(11):4069-4079. PMID: 17989126

18. Weingarten TN, Cata JP, O'Hara JF, et al. Comparison of two preoperative medical management strategies for laparoscopic resection of pheochromocytoma. Urology. 2010;76(2):508.e6-11. PMID: 20546874

19. Prys-Roberts C, Farndon JR. Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. World J Surg. 2002;26(8):1037-1042. PMID: 12016486

20. Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg. 2000;91(5):1118-1123. PMID: 11049893

21. Brunaud L, Nguyen-Thi PL, Mirallie E, et al. Predictive factors for postoperative morbidity after laparoscopic adrenalectomy for pheochromocytoma: a multicenter retrospective analysis in 225 patients. Surg Endosc. 2016;30(3):1051-1059. PMID: 26092024

Intraoperative Management

22. Desmonts JM, Marty J. Anaesthetic management of patients with phaeochromocytoma. Br J Anaesth. 1984;56(7):781-789. PMID: 6375709

23. Naranjo J, Dodd S, Martin YN. Perioperative Management of Pheochromocytoma. J Cardiothorac Vasc Anesth. 2017;31(4):1427-1439. PMID: 28372931

24. Lord MS, Augoustides JG. Perioperative management of pheochromocytoma: focus on magnesium, clevidipine, and vasopressin. J Cardiothorac Vasc Anesth. 2012;26(3):526-531. PMID: 22104532

25. James MF, Cronje L. Pheochromocytoma crisis: the use of magnesium sulfate. Anesth Analg. 2004;99(3):680-686. PMID: 15333394

Post-operative Complications

26. Zeiger MA, Thompson GB, Duh QY, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas. Endocr Pract. 2009;15 Suppl 1:1-20. PMID: 19632968

27. Challis BG, Casey RT, Simpson HL, Gurnell M. Is there an optimal preoperative management strategy for phaeochromocytoma/paraganglioma? Clin Endocrinol (Oxf). 2017;86(2):163-167. PMID: 27882574

Special Populations

28. Wing LA, Conaglen JV, Meyer-Rochow GY, Elston MS. Paraganglioma in Pregnancy: A Case Series and Review of the Literature. J Clin Endocrinol Metab. 2015;100(8):3202-3209. PMID: 26052726

29. Biggar MA, Lennard TW. Systematic review of phaeochromocytoma in pregnancy. Br J Surg. 2013;100(2):182-190. PMID: 23180595

30. Mannelli M, Ianni L, Cilotti A, Conti A. Pheochromocytoma in Italy: a multicentric retrospective study. Eur J Endocrinol. 1999;141(6):619-624. PMID: 10601966

Malignant Disease

31. Ayala-Ramirez M, Feng L, Johnson MM, et al. Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab. 2011;96(3):717-725. PMID: 21190975

32. Jimenez C, Rohren E, Habra MA, et al. Current and future treatments for malignant pheochromocytoma and sympathetic paraganglioma. Curr Oncol Rep. 2013;15(4):356-371. PMID: 23689775

Imaging

33. Timmers HJ, Chen CC, Carrasquillo JA, et al. Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2009;94(12):4757-4767. PMID: 19864450

34. Janssen I, Blanchet EM, Adams K, et al. Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res. 2015;21(17):3888-3895. PMID: 25934891

Australian Context

35. Sidhu PS, Allinson J, Russell CF. Phaeochromocytoma: a 15-year review of cases in Northern Ireland. Ulster Med J. 1999;68(2):64-68. PMID: 10609919

36. Russell CF, Hamid Q, Johnston PS. The surgical management of phaeochromocytoma: a 22-year experience. Ulster Med J. 2003;72(1):3-10. PMID: 12868636

Historical and Foundational

37. Cryer PE. Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med. 1980;303(8):436-444. PMID: 6248784

38. Goldstein DS. Catecholamines and stress. Endocr Regul. 2003;37(2):69-80. PMID: 12932191

39. Manger WM, Gifford RW. Pheochromocytoma. J Clin Hypertens (Greenwich). 2002;4(1):62-72. PMID: 11821644

40. Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601-610. PMID: 17287480

Additional Key References

41. Baguet JP, Hammer L, Mazzuco TL, et al. Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients. Eur J Endocrinol. 2004;150(5):681-686. PMID: 15132724

42. Agrawal R, Mishra SK, Bhatia E, et al. Prospective study to compare peri-operative hemodynamic alterations following preparation for pheochromocytoma surgery by phenoxybenzamine or prazosin. World J Surg. 2014;38(3):716-723. PMID: 24135766

43. Randle RW, Balentine CJ, Pitt SC, et al. Selective versus non-selective alpha-blockade prior to laparoscopic adrenalectomy for pheochromocytoma. Ann Surg Oncol. 2017;24(1):244-250. PMID: 27638677

44. Groeben H, Walz MK, Nottebaum BJ, et al. International multicentre review of perioperative management and outcome for catecholamine-producing tumours. Br J Surg. 2020;107(2):e170-e178. PMID: 31922612

45. Buitenwerf E, Osinga TE, Timmers HJLM, et al. Efficacy of alpha-blockers on hemodynamic control during pheochromocytoma resection: a randomized controlled trial. J Clin Endocrinol Metab. 2020;105(7):dgaa185. PMID: 32271377

46. Scholten A, Cisco RM, Vriens MR, et al. Pheochromocytoma crisis is not a surgical emergency. J Clin Endocrinol Metab. 2013;98(2):581-591. PMID: 23284005

47. Chen H, Sippel RS, O'Dorisio MS, et al. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010;39(6):775-783. PMID: 20664476

48. Conzo G, Musella M, Corcione F, et al. Laparoscopic adrenalectomy, a safe procedure for pheochromocytoma. A retrospective review of clinical series. Int J Surg. 2013;11(2):152-156. PMID: 23267851

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Related Topics

Prerequisites

• Adrenal Crisis
• Endocrine Physiology
• Shock States
• Autonomic Pharmacology

Related Conditions

• Thyroid Storm
• Hypertensive Emergency
• Cardiomyopathy
• Arrhythmias

Complications

• Catecholamine Cardiomyopathy
• Hypoglycaemia
• Adrenal Insufficiency

Procedures

• Arterial Line Insertion
• Central Venous Catheterisation

Pharmacology

• Vasoactive Agents
• Antihypertensive Agents