Paraganglioma (Phaeochromocytoma) Crisis

Author(s): James Crane and Paul Carroll

Paragangliomas (phaeochromocytomas; see Box 94.1) can present with life-threatening catecholamine-induced crises:

Hypertensive crisis (which may be complicated by encephalopathy, heart failure, myocardial infarction, or aortic dissection)
Atrial and ventricular arrhythmias
Hypotensive crisis (through poorly understood mechanisms)
Multi-organ crisis, characterized by hyperpyrexia, encephalopathy, acute kidney injury and pulmonary oedema

Crises may be triggered by administration of drugs, such as dopamine antagonists, tricyclic antidepressants, radiocontrast media or anaesthetic agents.

Manipulation of the tumour is likely to trigger a crisis in a patient without sufficient alpha-adrenergic blockade and exclusion of catecholamine excess is necessary prior to surgery on any tumour located at a site typical for paragangliomas.

Priorities ⬆ ⬇

In the patient presenting with a suspected catecholamine-induced crisis (Table 94.1), the following goals should be achieved in the first hour of treatment:

Rapid assessment of airway, breathing, circulation and conscious level in a level 2 or 3 environment, with continuous monitoring of heart rate, blood pressure and arterial oxygen saturation. Consider an arterial line for invasive monitoring.
Airway management by competent staff if the airway is compromised or the Glasgow Coma Scale score is less than 8.
Supplemental oxygen if needed to maintain SaO₂>94%.
Intravenous access with blood sent for urgent investigation (Table 94.2).
Assess for organ failure:
- Cardiovascular – arrhythmias, heart failure, ischaemic stroke, intracranial bleed, vasospastic peripheral ischaemia, myocardial infarction, aortic dissection or aneurysmal rupture
- Respiratory – pulmonary oedema
- Neurological – encephalopathy
- Renal – acute kidney injury
- Haematolgical – disseminated intravascular coagulation
In the absence of organ failure, see Further management for advice on commencing alpha blockade with oral phenoxybenzamine. If organ failure is present, intravenous alpha blockade may be necessary. Phentolamine is the preferred agent, delivered as a slow IV push of 1 mg over 1 min, with blood pressure monitoring via an arterial line. Caution is required; the circulating volume may be substantially reduced as a physiological response to increased vascular resistance. When reversed rapidly, a dramatic fall in blood pressure may ensue. Intravenous alpha blockade must be accompanied by aggressive intravenous filling to replace this missing volume as the arterial resistance falls.
Identify the precipitant and commence appropriate management.
Involve a specialist endocrinology team at the earliest opportunity.

Further Management ⬆ ⬇

Outline

Biochemical Confirmation
Imaging
Adrenergic Blockade
Multidisciplinary Management
Consider a Genetic Syndrome

Biochemical Confirmation

If organ failure is not present, confirmation of pathological elevation of catcholamines should be sought by measuring catecholamines or their metabolites (metanephrines) in the urine or blood. Plasma metanephrine levels are the most specific of these tests and less susceptible to the effects of intercurrent illness than levels of adrenaline or noradrenaline themselves. The vast majority of paragangliomas will secrete one or both of these hormones, pure dopamine-secreting paragangliomas are very rare.

Imaging

Dedicated cross-sectional imaging (CT or MRI) of the adrenal glands should be undertaken to localize the tumour. If negative, imaging from neck to pelvis is required.

Functional imaging is also useful as it may identify metastases and/or confirm uptake of a tracer by malignant paragangliomas, which may then be utilized in targeted radiotherapy should this be necessary post-surgery (peptide-receptor radionuclide therapy). I131-meta-IodoBenzylGuanidine (mIBG) is most commonly used.

Adrenergic Blockade

Alpha blockade using phenoxybenzamine at an initial dose of 10 mg 12-hourly PO should be initiated once the diagnosis is confirmed. This carries a risk of inducing profound hypotension (see above) and is best undertaken as an inpatient. This allows for more rapid up-titration of the dose and more accurate fluid replacement as the degree of alpha blockade increases. The dose is sequentially increased until normotension is achieved or adverse effects (chiefly nasal congestion and postural hypotension) become intolerable.

Beta blockade to control tachycardia or tachyarrhythmia may safely be commenced once adequate alpha blockade is in place.

Multidisciplinary Management

Early involvement of the surgical team to plan surgery is important, and management of paragangliomas is best under a multidisciplinary team of endocrinologists, endocrine surgeons, radiologists and nuclear medicine physicians.

Consider a Genetic Syndrome

In those with family history or who are aged <40, the possibility of a genetic syndrome should be considered. Evidence of neurofibromatosis type 1 (café-au-lait spots, cutaneous neurofibromata), multiple endocrine neoplasia type 2A (medullary thyroid cancer, hyperparathyroidism) or type 2B (as for type 2A plus Marfanoid habitus, and mucosal ganglioneuromas) and von Hippel Lindau (haemangioblastoma, renal cell cancer, pancreatic islet cell tumours) should be sought. If genetic testing confirms a diagnosis of these conditions or of SDH mutation, appropriate cascade screening of family members is necessary and referral to a clinical geneticist is required.

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Information ⬇

Priorities ⬆ ⬇

Further Management ⬆ ⬇

Further Reading ⬆