Phaeochromocytoma

This includes catecholamine secreting tumours of the adrenal medulla, extra-adrenal paragangliomas, familial phaeochromocytoma, Von Hippel Lindau and succinate dehydrogenase mutations. Diagnosis is usually made by measuring elevated urine metanephrines.

Baseline investigations - all patients 

2x24hr urinary metanephrines

Urinary metanephrines are the most sensitive and specific, widely available screen for phaeochromocytoma.

All patients with strongly positive results (>3x upper limit of normal) should be considered as having a phaeochromocytoma requiring immediate treatment and investigation.

Patients with results between 1-3x the upper limit of normal require further assessment with a serum metanephrine in the first instance. False positives may be found within this range, for example from interfering medication or obstructive sleep apnoea.

Patients with normal results should be reassured as false negatives are very rare.

Full blood count

Anaemia is a useful indicator of underlying disease, in particular malignancy. 

Urea and electrolytes

Useful indicator of general health and underlying disease.

Liver function test

Abnormal liver function testing should prompt liver ultrasound to seek metastatic disease, although it can have many other causes.

Bone profile

Hypercalcaemia may occur with thyrotoxicosis or malignancy.

Fasting glucose

Hypoglycaemia may mimic the clinical features of a phaeochromocytoma.

Thyroid stimulating hormone

A low thyroid stimulating hormone is highly suggestive of thyrotoxicosis, which may mimic the features of a phaeochromocytoma.

Free thyroxine

The combination of a suppressed thyroid stimulating hormone and elevated free thyroxine confirms thyrotoxicosis which should be treated before reassessing symptoms and considering whether further investigation is indicated.

Electrocardiogram

ECG should be performed in all patients at baseline to document and confirm any arrhythmias or other changes.

Further investigations - selected cases only

Urine catecholamines

This test has a high incidence of false negatives and so has been superceded by metanephrines.

Serum metanephrines

Serum metanephrines are usually taken in a patient after 15 minutes resting recumbent. It is highly sensitive and specific for phaeochromocytoma and is usually performed to confirm the diagnosis after a positive or borderline urinary collection.

Urine vanillylmandelic acid

Urinary VMA testing has a very high incidence of false positives and so has been superceded by metanephrines.

Clonidine suppresion test

Clonidine testing is occassionally useful in cases where there is hypertension and modest elevations of urine metanephrines (<4xULN). These grey cases can usually be resolved by taking a careful medication history, seeking evidence of sleep apnoea or by checking serum metanephrines as a normal result will effectively exclude a phaeochromocytoma. If no cause has been found, the clonidine test may be useful though it is expensive, timely and poorly tolerated by most patients. Clonidine acts via the alpha preganglionic receptors and should reduce catecholamine secretion. This test confirms the absence of phaeochromocytoma if noradrenaline levels suppress to normal and less than 50% basal, and metanephrines have fallen by greater than 40% or to within the normal range. 

Chest radiograph

Approximately 10% of patients with phaeochromocytoma have malignant disease.

Echocardiogram

This is frequently indicated in the assessment of a patient with a confirmed phaeochromocytoma to aid cardiac assessment.

Abdominal computerised tomography CT

Approximately 90% patients presenting with catecholamine secreting tumours have adrenal phaeochromocytomas. Approximately 10% will have bilateral disease, 10% malignant and 10% extra-adrenal paragangliomas.

Patients with possible familial syndromes, in particular VHL, SDHB or neurofibromatosis 1 mutations, will require imaging of the entire abdomen to seek renal, pancreatic or gastrointestinal stromal tumours.

Adrenal MRI

Depending on the features of the CT scan, some radiologists and surgeons may request an MRI to further delineate the characteristics and anatomy of an adrenal lesion.

Where familial disease is suspected, MRI imaging is preferred as it prevents the repeated exposure to ionising radiation with multiple CT scans.

Meta-iodobenzylguianidine scan

Phaeochromocytomas typically take up meta-iodobenzylguianidine (MIBG), and this scan is usually performed routinely prior to surgery.

MIBG scanning is also helpful to locate extra-adrenal disease and to determine whether there are multiple lesions.

Baseline pituitary function

Prolactin, luteinising hormone, follicle stimulating hormone, estradiol/testosterone, sex hormone binding globulin, IGF-1, growth hormone and 9am cortisol should be assessed as well as thyroid function at diagnosis.

Menopausal flushing can occasionally be mistaken for a phaeochromocytoma.

Phaeochromocytoma are strongly associated with multiple endocrine neoplasia type 2, but may occasionally be associated with pituitary tumours in the context of multiple endocrine neoplasia type 1.

Fasting gut hormones

Gut hormones should be tested when indicated, because of the rare association of phaeochromocytoma with multiple endocrine neoplasia type 1.

PTH

This should be assessed at baseline in patients with a confirmed phaeochromocytoma and repeated if calcium rises, due to the association between phaeochromocytoma and parathyroid hyperplasia in MEN 2a.

Calcitonin

This is mandatory due to the high penetrance of medullary cell carcinoma with multiple endocrine neoplasia type 2.

Consider further cross sectional imaging if indicated

If the MIBG scan suggests increased uptake in extra-adrenal regions these should be imaged appropriately after discussion with a radiologist.

Ophthalmology review and fluoroscein angiography

This should be arranged in patients with VHL at diagnosis and then on an annual basis to detect changes early and preserve vision.

Audiological testing

Audiometry is recommended at diagnosis, and then if hearing loss is suspected in patients with confirmed Von Hippel Lindau only.

Whole brain MRI scan

This is necessary at diagnosis and subsequently every three years in patients with VHL to detect and monitor haemangioblastomas.

Consider genetic testing and referral to a clinical geneticist for family screening

Discuss genetic testing, family screening and future surveillance imaging for patients presenting with extra-adrenal paragangliomas at any age, for patients presenting with a phaeochromocytoma at a young age (<45 years is recommended by some institutions, <20 by others), or for patients with other features suggestive of syndromic diseae: skin changes, mucosal neuromas, hypercalcaemia, malignant or multifocal disease and thyroid cancer.