Von Hippel Lindau

Autosomal dominant condition comprising haemangioblastomas of the retina and central nervous system, phaeochromocytomas, and renal cell carcinomas and angiomas. The diagnosis is confirmed by genetic testing.

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

Useful indicator of general health. Polycythaemia may occur with renal tumours. 

Urea and electrolytes

Useful indicator of general health and underlying disease.

Bone profile

Hypercalcaemia may occur with malignant disease.

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 baselne to document and confirm any arrhythmias or other changes.

Serum metanephrines

This test is 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.

Further investigations - selected cases only

Urine catecholamines

This test has a high incidence of false negatives and so has been superceded by metanephrines.

Clonidine suppression testing

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. 

Urine vanillylmandelic acid

Urinary VMA testing has a very high incidence of false positives and so has been superceded by urinary metanephrines.

Chest radiograph

This is a simple screen for metastatic or 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

Patients with VHL will require imaging of the entire abdomen to seek renal, pancreatic or gastrointestinal stromal tumours, as well as phaeochromocytomas. However, since they also require imaging of the nervous system, and since screening will need to continue lifelong, MRI is preferred.

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.

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 and spinal cord MRI scan

Whole brain MRI and spinal cord is necessary at diagnosis of VHL to detect haemangioblastomas. Surveillance imaging should then be repeated at least every three years, or sooner if clinically indicated, or if lesions have been detected.

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.