Phaeochromocytoma

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.

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

Useful indicator of general health and underlying disease.

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

Hypercalcaemia may occur with thyrotoxicosis or malignancy.

Hypoglycaemia may mimic the clinical features of a phaeochromocytoma.

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

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.

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

This test has a high incidence of false negatives and so has been superceded by metanephrines.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

Urinary VMA testing has a very high incidence of false positives and so has been superceded by metanephrines.

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. 

Approximately 10% of patients with phaeochromocytoma have malignant disease.

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

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.

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.

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.

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.

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

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.

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

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

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

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

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

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.