Published: 1 December 2022

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Pheochromocytoma crisis and systemic corticosteroids

Prescriber Update 43(4): 64–65
December 2022

Medsafe has asked sponsors of systemic corticosteroid medicines to update their data sheets with a warning for pheochromocytoma crisis. This article provides information about pheochromocytomas and pheochromocytoma crisis.

Pheochromocytoma

Pheochromocytomas are tumours that arise from chromaffin cells of the adrenal medulla.¹ They typically secrete one or more catecholamines: epinephrine, norepinephrine and dopamine.² Pheochromocytomas are rare, with an estimated annual incidence of approximately 0.8 per 100,000 person-years.¹

Pheochromocytoma predominantly presents with paroxysmal or sustained hypertension, plus episodic headache, tachycardia and sweating due to excessive catecholamine release.^1,3 Diagnosis requires proof of excessive catecholamine release and anatomical documentation of the tumour.⁴ The standard treatment for pheochromocytoma is generally pre-operative preparation with an alpha- and beta-blocker and surgical resection.^3,4

Pheochromocytoma crisis

Pheochromocytoma crisis (PC) is a rare, life-threatening endocrine emergency in which a pheochromocytoma releases high levels of catecholamines.⁵ PC can be associated with high mortality rates.⁶

The clinical presentation of PC ranges from severe hypertension to circulatory failure and shock, with subsequent involvement of multiple organ systems, including the cardiovascular, pulmonary, neurological, gastrointestinal, renal, hepatic and metabolic systems.⁶ PC can therefore be difficult to diagnose if the patient is not already known to have a pheochromocytoma, as it may mimic other life-threatening conditions.⁵

Management includes initial medical stabilisation of the acute crisis followed by sufficient alpha blockade before surgery.⁶

PC can occur spontaneously or be triggered by tumour resection, trauma, certain medicines (eg, corticosteroids, beta-blockers, metoclopramide, anaesthetic agents) or stress from nonadrenal surgery.^2,6

Corticosteroid-induced pheochromocytoma crisis ⁵

Although several hypotheses exist, the mechanism by which systemic corticosteroids trigger PC is not confirmed. Corticosteroids may potentiate the action of catecholamines on peripheral vessels and the heart, potentially leading to vasculopathy, tissue necrosis and haemorrhage. Increased corticosteroid receptor expression may mediate pheochromocytoma tumour sensitivity to corticosteroids and trigger catecholamine synthesis, production and release.

Consider PC as a differential diagnosis in patients treated with systemic dexamethasone or other corticosteroid products and who present with severe haemodynamic instability, shock, arrhythmia, cardiac ischaemia, or other symptoms suggestive of adrenergic crisis.

Data sheet update

PC is a rare but life-threatening condition. Therefore, Medsafe has requested that sponsors of systemic corticosteroids include the following warning in their data sheets:

Pheochromocytoma crisis. Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.

As of 30 September 2022, there have been no New Zealand reports of PC following administration of systemic corticosteroids.

References

1. Young W. 2022. Clinical presentation and diagnosis of pheochromocytoma. In: UpToDate 2 May 2022. URL: uptodate.com/contents/clinical-presentation-and-diagnosis-of-pheochromocytoma (accessed 8 June 2022).
2. Lenders J, Duh Q-Y, Eisenhofer G, et al. 2014. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism 99(6): 1915-42. DOI: https://doi.org/10.1210/jc.2014-1498 (accessed 16 June 2022).
3. Kakoki K, Miyata Y, Shida Y, et al. 2015. Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review. BMC Research Notes 8(Dec 9): 758. DOI: 10.1186/s13104-015-1738-z (accessed 8 June 2022).
4. Neumann H, Young W and Eng C. 2019. Pheochromocytoma and paraganglioma. New England Journal of Medicine 381(6): 552-65. DOI: 10.1056/NEJMra1806651 (accessed 16 June 2022).
5. Health Canada. 2021. Systemic corticosteroids (including dexamethasone) and pheochromocytoma crisis when administered to patients with identified, suspected or unsuspected pheochromocytoma. Health Product Info Watch May 2021: 4–6. URL: canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/medeffect-canada/health-product-infowatch/may-2021/hpiw-ivps_2021-05-eng.pdf (accessed 16 June 2022).
6. Scholten A, Cisco R, Vriens M, et al. 2013. Pheochromocytoma crisis is not a surgical emergency. Journal of Clinical Endocrinology & Metabolism 98(2): 581-91. DOI: https://doi.org/10.1210/jc.2012-3020 (accessed 16 June 2022).