a 44 year old male presents to your Emergency Department with severe, crushing retrosternal chest pain. He reports that the pain started suddenly approximately one hour ago whilst at rest.
It is described as a retrosternal pressure or tightness which radiates up to his neck, through to the back & down towards his umbilicus.
The pain is associated with severe palpitations. There is no associated dyspnoea, cough or haemoptysis. There have been no syncopal or near-syncopal episodes and he has no neurological symptoms. He has never had pain like this before.
Past Medical History:
No significant social history.
He looks unwell. He is profoundly clammy and diaphoretic.
- A: Patent & protected.
- B: Tachypnoeic (28 breaths per minute), minimal work of breathing. SaO2 95% (RA). Chest clear to auscultation.
- C: Pulse rate 135 per minute, Blood pressure 190/110 (no differential between left & right arms). Good peripheral pulses without pulse deficit. Heart sounds dual without murmurs or rub.
- D: GCS 15. Equal and reactive pupils (4mm). Moving all 4 limbs. No focal motor or sensory changes.
- E: Temperature 37.7*C. Blood glucose 8.2 mmol/L.
You can’t help but notice that he has a new dressing over his left deltoid. When you enquire about this, he tells you that earlier that day he underwent an elective resection of a skin lesion under general anaesthetic at a nearby hospital. This was apparently an uneventful procedure & recovery and he was discharged home only a few hours ago.
- Narrow complex (sinus) tachycardia at a rate of ~140 beats per minute.
- Normal axis.
- ~1mm of ST segment elevation in aVR with diffuse, widespread ST segment depression (V3-6, I & aVL)
- PR & QRS intervals normal.
- Prolonged QT interval.
Differential diagnoses include;
(1) left main coronary artery occlusion
(2) proximal LAD occlusion
(3) severe triple vessel disease
(4) diffuse sub-endocardial ischaemia (myocardial O2 supply/demand mismatch)
- Severe metabolic acidosis:
- HCO3 13, BE -15.
- Uncompensated with a pH 7.17
- Exp pCO2 = (1.5×13) + 8 = 20 + 8 = 28.
- Actual = 37, therefore a contributing relative respiratory acidosis.
- High anion gap (Cl = 102)
- 141 – (102+13) = 26
- Severely elevated lactate: 15mmol/L !!
- DDx: sepsis, hyperadrenergic state, ingestion, malperfusion/ischaemia, MH
- Severe hyperglycaemia: 28 mmol/L
- ?new onset diabetes ?stress response
- Are there ketones contributing to the acidosis?? In this case, they were normal.
- Mild hypokalaemia:
- K 3.8mmol/L, however when corrected for acidosis is more likely <3!
- Mildly elevated serum creatinine.
- ?acute vs chronic
- ?contributory vs incidental finding
- Hb 170
- Normal cardiomediastinal contour.
- Clear lung fields without collapse or consolidation.
- No pleural effusions.
- Acute coronary syndrome
- Aortic dissection
- Hypertensive crisis – but why?
- Malignant hyperthermia (cases of delayed onset MH have been reported)
- Thyroid storm
- Sympathomimetic toxidrome
- Anticholinergic toxidrome
- Serotonin syndrome
- Neuroleptic malignant syndrome
- Salicylate toxicity
- Methylxanthine toxicity
- IV access
- Titrated intravenous opiates is suitable (eg. Fentanyl 50mcg IV q5-10mins)
- Easier (& quicker) to start with a sublingual tablet followed by infusion for blood pressure control & reduction of ongoing ischaemic chest pain
- Detect and correct electrolyte derangement especially potassium
With a strong clinical suspicion for aortic dissection, antiplatelet therapy & anticoagulation are withheld and a CT Aortogram is arranged urgently…
Upon return from radiology, he continues to complain of severe retrosternal pain…
His pulse remains 136 per minute with a blood pressure of 196/118 mmHg despite your GTN infusion now running at 250 micrograms per minute.
The nurse looks at you and asks, “What are we going to do now??”
Phaeochromocytoma is a catecholamine-secreting neuroendocrine tumour (a paraganglioma), most frequently arise from the chromaffin cells of the adrenal medulla.
- Incidence is very low ~2 people/million/year.
- Most common between ages of 20 and 50 years.
- 50% of cases are diagnosed only at post-mortem examination.
- “10% rule”
- Bilateral in 10% of cases
- 10% are extra-adrenal
- 10% are malignant
- ~10% are found in children
- ~10% are familial
- Phaeochromocytomas are the secondary cause of hypertension in 0.1% of hypertensive patients.
- A proportion of patients are diagnosed at the time of incidental surgery when induction of anaesthesia may precipitate a hypertensive crisis.
- Mortality in this instance is close to 80%.
Classically, phaeochromocytoma manifests as spells with the following 3 characteristics…
These spells may or may not be associated with severe hypertension.
Typical patterns of the spells are as follows:
- Frequency may vary from monthly to several times per day
- Duration may vary from seconds to hours
- Over time, spells tend to occur more frequently and become more severe as the tumour grows.
The typical features of phaeochromocytoma are predominantly cardiovascular:
- Paroxysmal (~45%)
- Sustained (50%)
- NB. ~5% are normotensive
- Palpitations and tachycardia
- Chest pain (± myocardial infarction)
- Cardiac failure (± acute pulmonary oedema)
Other symptoms include;
- Anxiety or a sense of doom
- Epigastric pain
- Flank pain
“Clinical suspicion remains the single most important factor in
the identification of phaeochromocytoma.“
Phaeochromocytomas can present as a component of familial syndromes (esp. thyroid cancers). It is important to be aware of this association.
Measurements of urinary catecholamines and their metabolites, metanephrines, over 24 hours have been the mainstay of biochemical diagnosis of phaeochromocytoma for many years (Sn 88%, Sp 99%).
Tests for catecholamines and their metabolites
- Urinary catecholamines
- Plasma catecholamines
- Urinary fractionated metanephrines
- Plasma free metanephrines (these appear to be the best single investigation)
- Urinary vanillylmandelic acid
Clonidine suppression test
In patients with phaeochromocytoma, serum catecholamine levels will not decrease in response to clonidine (they are independent of neurogenic control).
- CT scan (including dedicated adrenal study with washout)
- Nuclear medicine (esp.I-123 MIBG)
- PET scan
Check for alternate diagnoses:
- Thyroid function (TSH, T4)
- Plasma renin activity
- Cortisol levels (plasma & urine)
Phaeochromocytoma is known for life-threatening acute hypertensive emergencies, as well as clinical consequences of long-lasting hypertension.
Spells or crises can result from a variety of precipitants including;
- Postural changes, physical exertion, emotion
- Certain foods or beverages (especially those with tyramine eg. cheese, beer, wine)
- Direct tumour stimulation (abdominal pressure or injury)
- histamine, ACTH, metoclopramide, phenothiazine, TCAs or anaesthetic agents.
Organ-Specific Hypertensive Complications
- Acute coronary syndromes (including myocardial infarction)
- Cardiomyopathies (incl. Takotsubo)
- Heart failure including pulmonary oedema and cardiogenic shock
- Hypertensive encephalopathy
- Postural hypotension
- Aortic dissection
- Organ ischaemia
- Limb ischaemia
- Acute renal failure
- Intestinal ischaemia (necrosis or peritonitis)
- Acute blindness
- Multisystem failure
This complication consists of multiple organ system failure
- Fever over 40°C
- Severe hypertension and/or hypotension
- Pulmonary oedema
- Anuric acute renal failure
Management of phaeochromocytoma-related emergencies depends on the symptoms; however, it should always include pharmacologic treatment to block the effects of high levels of circulating catecholamines and prevent life-threatening catecholamine-induced complications.
This review will not cover the pre-operative management of these patients.
- Control of hypertension.
- Rapidly acting α-1 antagonist:
- Phentolamine: 0.5-1mg per minute in aliquots or via infusion.
- Slowly acting non-competitive α-1 antagonist:
- Phenoxybenzamine reserved for post-crisis care & pre-op optimisation
- Sodium nitroprusside
- β-blockers (only after adequate α-blockade) – eg. atenolol or propranolol
- Calcium channel blockers
- Rapidly acting α-1 antagonist:
- Maintenance of circulating volume in the face of vasodilation.
- IV fluid replacement
- Control of atrial fibrillation.
- Verapamil, diltiazem or amiodarone
- Assessment of myocardial damage.
- Seek and treat precipitating cause
- Admit for further workup & operative planning
Definitive treatment is surgical removal and if complete resection is achieved, without metastases, then surgery is curative in >90% of cases. Following this, hypertension usually resolves.
Following confirmation of the adrenal lesion, the patients blood pressure is managed acutely with a high-dose GTN infusion and aliquots of phentolamine. He is subsequently admitted to the Intensive Care Unit for ongoing short-term care.
Over the following 48 hours he is transitioned onto oral antihypertensives, in this case, prazosin.
His 24-hour urinary collection demonstrated;
A subsequent dedicated adrenal CT demonstrated an absolute washout of 79%.
Here is his I-123 MIBG scan…
After 5 days in hospital, he was discharged home with ongoing specialist input. He later underwent a successful, elective surgical resection of his phaeochromocytoma & is doing well…
- Alderazi Y, Yeh MW, Robinson BG. Phaeochromocytoma: current concepts. The Medical journal of Australia. 2005; 183(4):201-4. [pubmed]
- Zuber SM, Kantorovich V, Pacak K. Hypertension in pheochromocytoma: characteristics and treatment. Endocrinology and metabolism clinics of North America. 2011; 40(2):295-311, vii. [pubmed]
- Myklejord DJ. Undiagnosed Pheochromocytoma: The Anesthesiologist Nightmare Clinical Medicine & Research. 2004; 2(1):59-62. [pubmed]
- Pacak K, Eisenhofer G, Ahlman H. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005. Nature clinical practice. Endocrinology & metabolism. 2007; 3(2):92-102. [pubmed]
- Frederick MJ, Colwell AS. Acute hypertensive crisis secondary to pheochromocytoma during elective cosmetic surgery. Plastic and reconstructive surgery. 2015; 135(1):238e-9e. [pubmed]
- Bensghir M, Elwali A, Lalaoui S et al. Management of undiagnosed pheochromocytoma with acute appendicitis World J Emerg Surg. 2009; 4(1):35. [pubmed]
- Raut M, Kar S, Maheshwari A et al. Rare postoperative delayed malignant hyperthermia after off-pump coronary bypass surgery and brief review of literature Ann Card Anaesth. 2016; 19(2):357-362. [pubmed]