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
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.
Useful indicator of general health. Polycythaemia may occur with renal tumours.
Useful indicator of general health and underlying disease.
Hypercalcaemia may occur with malignant disease.
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 baselne to document and confirm any arrhythmias or other changes.
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
This test has a high incidence of false negatives and so has been superceded by metanephrines.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.
Urinary VMA testing has a very high incidence of false positives and so has been superceded by urinary metanephrines.
This is a simple screen for metastatic or malignant disease.
This is frequently indicated in the assessment of a patient with a confirmed phaeochromocytoma to aid cardiac assessment.
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.
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.
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.
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.
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.