Phaeochromocytoma

Phaeochromocytoma is a catecholamine secreting tumor arising from chromaffin cells of the adrenal medulla.

When an analogous tumor arises from extra-adrenal sympathetic paraganglia rather than the adrenal medulla itself, it is termed a paraganglioma. The two are often considered together given their shared biology and clinical presentation.

A meaningful proportion of cases, more than historically appreciated, arise in the context of an underlying hereditary syndrome. These include multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and hereditary paraganglioma syndromes from succinate dehydrogenase gene mutations.

Genetic counseling and testing is therefore now recommended for essentially all patients diagnosed with a phaeochromocytoma or paraganglioma, regardless of whether an obvious family history is present.

The classic presentation is paroxysmal, with episodic symptoms from a surge of catecholamine release. A substantial proportion of patients have persistent, sustained hypertension rather than a purely episodic pattern. A smaller proportion are entirely asymptomatic, with the tumor identified incidentally on imaging performed for another reason.

The classic paroxysmal triad consists of episodic headache, sweating, and palpitations. These are often accompanied by a sense of anxiety or impending doom, pallor, and a significant surge in blood pressure during the episode.

Episodes may be triggered by specific factors, including certain medications, abdominal palpation, or, notably, induction of anesthesia. This is part of why the diagnosis should be actively considered and excluded before any planned surgery on a patient with an incidentally discovered adrenal mass.

Hypertension, whether paroxysmal or sustained, is a near universal feature and is often resistant to standard antihypertensive therapy. This should prompt consideration of a secondary cause, including phaeochromocytoma, particularly in a younger patient or one with other suggestive features.

Biochemical testing is the first step and should precede any imaging. Imaging findings, particularly incidentally discovered adrenal masses, are common in the general population and non-specific without biochemical confirmation of catecholamine excess.

Plasma free metanephrines or 24 hour urinary fractionatedmetanephrines are the preferred initial tests, offering high sensitivity for catecholamine excess. Metanephrines are continuously produced within the tumor regardless of the episodic nature of catecholamine release itself. They are therefore more reliable than measuring catecholamines directly, which can be normal between paroxysmal episodes.

Certain medications and circumstances can cause false positive results. Review medications carefully, including certain antidepressants and other agents affecting catecholamine metabolism or measurement. Consider the testing conditions (ideally with the patient supine and rested, avoiding caffeine and strenuous exercise beforehand) when interpreting borderline results.

Once biochemical confirmation is obtained, CT or MRI of the abdomen localizes the tumor. MRI is often preferred, particularly in younger patients given the avoidance of radiation, and given its good sensitivity for adrenal and extra-adrenal disease.

MIBG scintigraphy or, increasingly, PET imaging with specific tracers, provides functional confirmation. It is particularly useful for localizing extra-adrenal paragangliomas or identifying metastatic disease. Metastatic disease occurs in a meaningful minority of cases and cannot be reliably predicted from histology alone.

Genetic testing is recommended for essentially all confirmed cases, given the substantial proportion of hereditary disease. It has implications for the patient's own surveillance for other syndrome associated tumors as well as for family screening.

Differentials include other causes of paroxysmal hypertension and episodic symptoms, including panic disorder (see that entry) and hyperthyroidism. Importantly, they also include other causes of an incidentally discovered adrenal mass without catecholamine excess (adrenal adenoma, adrenal cortical carcinoma, metastasis).

Biochemical exclusion of a phaeochromocytoma is therefore a standard part of the workup for any incidentally discovered adrenal mass.

Surgical resection is the definitive treatment and offers the potential for cure in localized disease. It must never be undertaken without adequate preoperative alpha blockade. There is a risk of a catastrophic hypertensive crisis if the tumor is manipulated during surgery before adrenergic blockade is established.

Alpha blockade, typically with phenoxybenzamine or a selective alpha-1 blocker such as doxazosin, is started at least one to two weeks before planned surgery. Titrate it to achieve adequate blood pressure control.

Give a liberalized salt and fluid intake alongside it. This counteracts the volume contraction that chronic catecholamine excess causes, given the risk of significant hypotension once the tumor is removed and the catecholamine surge ceases.

Beta blockade is added only after adequate alpha blockade has been established, never before. Beta blockade in the presence of unopposed alpha adrenergic stimulation can precipitate a severe hypertensive crisis from unopposed vasoconstriction. This is an important and specific sequencing principle in the preoperative preparation of these patients.

Intraoperative and immediate postoperative management requires close hemodynamic monitoring, given the potential for significant blood pressure swings both during tumor manipulation and immediately after its removal.

Metastatic or unresectable disease is managed with a combination of continued alpha and beta blockade for symptom and blood pressure control. This is alongside systemic therapy directed at the tumor itself, guided by specialist endocrine oncology input. Options may include MIBG targeted radionuclide therapy for MIBG avid disease, or chemotherapy.

Lifelong follow up, including periodic biochemical testing, is recommended after resection given the risk of recurrence or metachronous disease, particularly in patients with an identified hereditary syndrome.

Referral: endocrinology for diagnosis and perioperative medical management; endocrine surgery for resection; genetic counseling for all confirmed cases given the substantial hereditary component.