Phaeochromocytoma and paraganglioma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Sympathetic PPGLs commonly secrete noradrenaline, adrenaline or dopamine-related products and produce cardiovascular symptoms. Many head-and-neck parasympathetic paragangliomas are non-secretory and present as a slow-growing neck mass, pulsatile tinnitus or cranial-nerve deficit. Biochemical phenotype, anatomical site and genotype together guide imaging and risk.

Metanephrines outperform random catecholamines because catechol-O-methyltransferase continuously metabolises tumour catecholamines. A carefully collected normal result makes a functional tumour unlikely, whereas a result several-fold above the reference interval is more concerning than a modest stress-associated elevation. The laboratory's posture-specific range and interference list are integral to interpretation.

Surgery is the preferred treatment for many localised sympathetic tumours, but safe surgery begins weeks earlier. Alpha blockade expands a chronically contracted circulating volume and limits intra-operative surges; salt and fluid intake are increased when appropriate. An experienced endocrine surgeon and anaesthetist anticipate hypertension during manipulation and hypotension after venous ligation.

Key points

Phaeochromocytoma arises from adrenal medullary chromaffin tissue; paraganglioma arises from extra-adrenal sympathetic or parasympathetic paraganglia. The umbrella abbreviation is PPGL.
The classic episodic triad is headache, sweating and palpitations, often with pallor, tremor or panic-like symptoms, but sustained hypertension, incidental imaging or no symptoms are also possible.
Catecholamine release can cause paroxysmal or sustained hypertension, orthostatic hypotension, cardiomyopathy, arrhythmia, myocardial injury, stroke, pulmonary oedema or multi-organ failure.
Plasma free or urinary fractionated metanephrines are preferred biochemical tests because metabolites are produced more continuously than episodically released catecholamines.
Sampling conditions, posture, acute illness, obstructive sleep apnoea, stress and several medicines produce false-positive metanephrines. Borderline elevation needs controlled repeat or specialist evaluation, not immediate surgery.
Establish biochemical evidence before localisation imaging in most non-emergency presentations. Once confirmed, CT or MRI and selected functional imaging define site, multiplicity and metastatic disease.
Never biopsy an adrenal or paraganglionic mass until phaeochromocytoma has been excluded; needle manipulation can provoke a catastrophic catecholamine crisis.
Pre-operative alpha-adrenoceptor blockade and salt/fluid preparation are supervised by a specialist MDT. Add beta-blockade only after adequate alpha blockade if tachycardia still requires it.
The MHRA made domperidone contraindicated in confirmed or suspected phaeochromocytoma in July 2026 because it can trigger severe hypertension; stop it and choose an alternative.
A substantial minority of PPGL is hereditary. NHS genomic assessment can identify RET, VHL, SDHx, MAX, TMEM127 and other susceptibility genes, changing surveillance and family care.
Metastatic potential is defined by spread to a site where chromaffin tissue is not normally present, not by benign-looking histology alone; long-term biochemical and imaging surveillance is required.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Adrenal chromaffin tumour

A phaeochromocytoma arises from adrenal medullary chromaffin cells and commonly produces catecholamine metabolites that drive cardiovascular symptoms.

Extra-adrenal paraganglioma

Sympathetic paragangliomas may secrete catecholamines, while many head-and-neck parasympathetic tumours present through mass or cranial-nerve effects.

Inherited tumour susceptibility

A substantial clinical subgroup has a germline predisposition, so age, site, multiplicity, family history and genotype inform wider surveillance.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Chromaffin cells proliferate
A neuroendocrine tumour develops within adrenal or paraganglionic tissue, with site and genotype influencing secretion and metastatic risk.
2
Catecholamine production becomes autonomous
Continuous catecholamine metabolism generates metanephrines even when episodic release makes symptoms and random catecholamine concentrations fluctuate between attacks.
3
Vascular and cardiac stress rises
Alpha- and beta-adrenergic effects cause vasoconstriction, tachycardia, labile blood pressure and increased myocardial oxygen demand while the condition remains active.
4
Manipulation can trigger a surge
Anaesthesia, tumour handling or certain medicines can release catecholamines abruptly, producing severe hypertension, arrhythmia or cardiovascular collapse.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Paroxysmal catecholamine spellsRed flag

Abrupt pounding headache, drenching sweat, forceful palpitations, pallor, tremor and fear lasting minutes to hours with episodic hypertension is the classic pattern. Attacks may be spontaneous or triggered by exertion, anaesthesia, drugs or tumour pressure.

Cardiovascular presentationRed flag

Labile or resistant hypertension, orthostatic hypotension, atrial or ventricular arrhythmia, Takotsubo-like cardiomyopathy, myocardial infarction with unobstructed arteries or unexplained pulmonary oedema should prompt contextual consideration.

Incidental adrenal mass

An adrenal lesion found on imaging requires functional review before biopsy or surgery. Absence of spells does not make it safe to manipulate without biochemical assessment.

Head and neck paraganglioma

A slowly enlarging lateral neck mass, pulsatile tinnitus, hearing change, hoarseness, dysphagia or lower cranial-nerve deficit can represent a parasympathetic paraganglioma, which may not elevate metanephrines.

Hereditary pattern

Young age, bilateral or multifocal tumours, recurrence, metastatic disease, head-and-neck location or family features of MEN2, VHL, NF1 or SDHx syndromes strengthens the indication for formal genomic assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Plasma free metanephrinesFirst step
Why
Detect functional PPGL using continuously produced catecholamine metabolites.
Interpretation and limitations
Follow the laboratory's rest, posture, fasting and transport instructions. Values more than several-fold above the upper interval are strongly suspicious; modest elevation is vulnerable to stress, posture and medicine interference.
02
Twenty-four-hour urinary fractionated metanephrines
Why
Provide an alternative integrated biochemical assessment when plasma collection conditions are impractical or results need corroboration.
Interpretation and limitations
Check collection completeness and renal context, and avoid collection during major acute stress when feasible. Use the assay's reference ranges rather than converting informally between platforms.
03
Medication and physiological interference review
Why
Prevent false-positive results and avoid drugs that provoke catecholamine release.
Interpretation and limitations
Review antidepressants, sympathomimetics, levodopa, alpha or beta blockers, caffeine/nicotine and acute illness with the laboratory. Do not stop essential therapy unsafely merely to normalise a test.
04
CT or MRI from skull base to pelvis as directed
Why
Localise and stage biochemically confirmed disease or characterise a known mass.
Interpretation and limitations
MRI is useful for head, neck, pregnancy and radiation avoidance; CT defines adrenal and thoracoabdominal anatomy. Imaging phenotype alone cannot prove secretion or exclude hereditary multifocality.
05
Functional nuclear imaging
Why
Identify multifocal, metastatic or occult disease and assess eligibility for radionuclide therapy.
Interpretation and limitations
MIBG, somatostatin-receptor PET or FDG PET selection depends on location, biochemical phenotype, genotype and treatment question, decided by the NET/nuclear-medicine MDT.
06
NHS genomic testing
Why
Identify a constitutional susceptibility variant that changes lifelong surveillance and family testing.
Interpretation and limitations
Use the NHS Genomic Test Directory indication and a genetics record-of-discussion process. Distinguish germline from tumour testing and offer cascade testing only through the genetics pathway.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Panic disorder

Palpitations, sweating and tremor overlap, but sustained or paroxysmal hypertension and valid metanephrine elevation support catecholamine tumour physiology.

Thyrotoxicosis

Heat intolerance, tremor and tachycardia with suppressed TSH and raised thyroid hormones indicate thyroid rather than chromaffin excess.

Medicine or stimulant effect

Decongestants, recreational stimulants and several prescribed medicines can reproduce symptoms or modestly disturb testing, making preparation and exposure review essential.

Essential hypertension

Common hypertension lacks the coherent biochemical, episodic or syndromic features, although an asymptomatic tumour can still be discovered incidentally.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Suspected functional PPGLBiochemistry before anatomyFirst stepCompatible spells, resistant/labile hypertension, adrenal mass or syndromic context without current crisis.

1Review symptoms, family history, blood-pressure pattern, all medicines and acute confounders, then select plasma or urinary metanephrines with the receiving laboratory's collection instructions.
2For borderline elevation, improve posture/rest and interference conditions and repeat or seek endocrinology advice. For marked elevation, expedite specialist referral and avoid provoking medicines and procedures.
3After biochemical evidence, obtain anatomic and selected functional imaging through the PPGL MDT; do not biopsy the lesion.

02Pre-operative preparationBlock alpha before betaLocalised secretory PPGL selected for surgery by the multidisciplinary team.

1Initiate phenoxybenzamine or a selective alpha-1 blocker under specialist monitoring, titrating seated and standing pressure and symptoms while progressively expanding salt and fluid intake when safe.
2If troublesome tachycardia persists after adequate alpha blockade, add beta-blockade cautiously; never start beta-blocker first because unopposed alpha vasoconstriction can cause crisis.
3Operate in an experienced adrenal/NET centre with invasive haemodynamic planning, blood availability and postoperative surveillance for hypotension, hypoglycaemia and adrenal insufficiency when relevant.

03Genetic and long-term careTreat the person and the predispositionConfirmed PPGL after immediate biochemical and anatomical management is established.

1Refer for NHS genomic testing and counselling according to current eligibility, explaining possible implications for kidneys, thyroid, parathyroids, other tumours and relatives depending on the gene.
2Use pathology, genotype, location, size and biochemical phenotype to set lifelong metanephrine and imaging surveillance; a normal postoperative scan is not automatic discharge.
3For unresectable or metastatic disease, use a specialist NET MDT to integrate blood-pressure control, surgery, radionuclide therapy, radiotherapy, systemic treatment and symptom-focused care.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Long-acting non-selective alpha blockade used before surgery and for catecholamine-related hypertension in selected PPGL care.

Phenoxybenzamine

Specialist initiation commonly begins at a low oral dose and is titrated over days to pressure and postural response using current BNF guidance.

Postural hypotension, tachycardia, nasal congestion and prolonged postoperative hypotension can occur. Expand volume carefully and coordinate with anaesthesia; pregnancy and major cardiac disease need individual review.

Alternative pre-operative alpha blockade with shorter action in centres whose PPGL protocol prefers a selective medicine.

Selective alpha-1 blocker

Agent and dose are chosen by the specialist centre and titrated to seated and standing blood pressure, symptoms and operative timing.

First-dose and postural hypotension occur, and shorter blockade does not remove intra-operative risk. Salt/fluid planning and experienced anaesthesia remain necessary.

Controls heart rate once alpha-mediated vasoconstriction has been neutralised in pre-operative or symptomatic management.

Beta-blocker after alpha blockade

Introduce only after adequate alpha blockade, at a specialist-selected dose for persistent tachycardia or arrhythmia with ECG and haemodynamic review.

Never use alone or first in suspected catecholamine-secreting PPGL because unopposed alpha stimulation can cause severe hypertension and pulmonary oedema. Check asthma and conduction disease.

This is a medicine-safety prohibition following the July 2026 MHRA contraindication for severe hypertensive episodes.

Domperidone avoidance

Do not administer in confirmed or suspected phaeochromocytoma; stop current treatment and select an alternative antiemetic after clinical review.

Domperidone can unmask disease. Severe hypertension after exposure requires emergency assessment; palliative-care use still needs an explicit individual benefit-risk decision.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Hypertensive crisis

A catecholamine surge can cause severe vasoconstriction, hypertensive encephalopathy, aortic injury, pulmonary oedema or other acute end-organ failure.

Cardiomyopathy and arrhythmia

Sustained adrenergic stimulation can injure myocardium, cause heart failure and provoke atrial or ventricular rhythm disturbance.

Stroke or myocardial injury

Extreme blood-pressure shifts and myocardial oxygen demand can precipitate cerebral haemorrhage, cerebral ischaemia, acute coronary injury or stress cardiomyopathy.

Metastatic or multifocal disease

Some tumours recur, spread or arise at multiple sites, especially in inherited disease, requiring long-term biochemical and imaging surveillance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During alpha blockade, record supine/seated and standing blood pressure, heart rate, nasal congestion, dizziness, weight and fluid status, with frequent specialist contact during titration.
Before and during surgery, use continuous haemodynamic and ECG monitoring; after tumour vein ligation watch for profound hypotension and check glucose for rebound hypoglycaemia.
After resection, repeat metanephrines at the specialist interval to establish biochemical response and use pathology and imaging to define residual or metastatic disease.
Maintain long-term biochemical and imaging surveillance based on genotype and tumour risk; investigate recurrent spells rather than assuming panic or surgical cure is permanent.
For variant carriers and relatives, keep surveillance within genetics/endocrine protocols and document which service recalls each person, preventing loss at transition between paediatric and adult care.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Metabolites smooth the signal

A tumour may release catecholamines in bursts, but intratumoural metabolism continues between spells. This is why metanephrines are generally more sensitive than a random adrenaline measurement.

Alpha first is physiology

Beta blockade removes vasodilation and cardiac buffering while alpha vasoconstriction remains active. The resulting pressure surge is avoidable by respecting treatment order.

A quiet tumour can be inherited

Head-and-neck paragangliomas may be non-secretory, yet carry meaningful SDHx-associated family and metastatic implications. Normal metanephrines do not erase a structural or genomic diagnosis.

Histology cannot promise benignity

PPGL malignant behaviour is established by metastasis to non-chromaffin sites. Surveillance continues even after apparently complete resection with reassuring microscopy.

The antiemetic list changes

The 2026 MHRA domperidone contraindication is a live prescribing update. Medication reconciliation in suspected PPGL should specifically remove it rather than relying on older teaching lists.

11Common pitfallsFrequent interpretation and management errors.

01
Dismissing episodic headache, sweat and palpitations as anxiety without checking the blood-pressure and medication context.
02
Interpreting a borderline seated metanephrine result during severe illness as definitive tumour proof.
03
Biopsying an adrenal mass before excluding catecholamine secretion.
04
Starting propranolol or another beta-blocker before adequate alpha blockade.
05
Prescribing domperidone after PPGL is suspected despite the current MHRA contraindication.
06
Treating a solitary tumour but omitting genomic counselling and long-term recurrence surveillance.