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.
Urine metanephrine strongly positive or plasma metanephrine positive
Ensure full investigation has been performed at baseline
At diagnosis of a phaeochromocytoma, a thorough assessment is required. This should include the following in all patients: thorough family history and documented family tree; 1x plasma metanephrine; chest radiograph; CT or MRI adrenals; MIBG scan; and further cross sectional imaging depending on results of MIBG scan.
Explain results and treatment options
Patients need to understand their diagnosis and the importance of adhering to medical treatment.
This is particularly important because the medication may not be well tolerated, but non compliance can have fatal consequences.
Initiate medical treatment with alpha blockade
Usual treatment starts with phenoxybenzamine 40mg in four divided doses daily if tolerated, and with BP monitoring.
This may have unpleasant side effects, for example dizziness, malaise and swollen ankles.
Sustained release doxazosin may be used if phenoxybenzamine is unavailable or not tolerated. Dose should be titrated to the maximum tolerated.
Add beta blockade
Once a patient is fully alpha blocked, typically after two weeks in an out patient setting, initiate beta blockade, for example with propranolol.
Close BP monitoring is again required and the dose should be increased to the maximum tolerated or 240mg in divided doses.
Arrange surgery
Ideally patients will have been fully alpha and beta blocked over a period of approximately six weeks prior to surgery.
Peri-operative management
Admit patients for intravenous alpha blockade prior to surgery.
If the patient is already on full oral treatment, administer intravenous phenoxybenzamine over three days prior to surgery. This aims to ensure absolute alpha blockade, and hence to reduce the risk of BP fluctuations during surgery.
Monitor postural blood pressure and haemoglobin over successive days. Patients frequently require intravenous fluid support for dramatic falls in blood pressure. Patients may also require pre-operative blood transfusions if haemoglobin falls, due to haemodilution as the vascular bed dilates and the intravascular volume expands. This preparation should prevent dramatic changes in blood pressure peri-operatively, although an anaesthetist experienced in this procedure is essential.
Emergency management
In the acutely unwell patient, or one presenting with a crisis, the first priority should be fluid resuscitation. This should prevent a catastrophic fall in blood pressure occurring when alpha blockade is initiated.
Beta blockade is added only after the patient appears to be fully alpha blocked which may take several days.
Post operative management
All medication may be stopped routinely.
Blood pressure should be closely monitored.
Arrange for urinary metanephrines to be repeated at six to 12 weeks.
Genetic counselling and screening
Counselling and screening of patients and family members for phaeochromocytomas, neurological, retinal, renal, pancreatic and epididymal and broad ligament tumours must be discussed.
Baseline investigations at diagnosis
At diagnosis, perform an MRI of the whole brain, spinal cord and abdomen and arrange audiological and ophthalmoligical reviews.
Annual follow up
There is no internationally agreed guideline on the follow up of VHL. However, the VHL family alliance recommends an annual screening programme.
Annual follow up must include a review of symptoms, blood pressure and family history. It should also include full blood count, urea and electrolytes, liver function test, glucose, 2x24hr urine metanephrines, urine microscopy, and ultrasound adrenal/kidney. An annual ophthalmology review with fluorescein angioscopy should also be arranged.
Further imaging
Chest radiograph, MRI brain and spine, and CT or MRI abdomen to image the adrenals, kidneys and pancreas should all be repeated at least every three years to age 50, then every five years.
Imaging should be repeated more frequently if clinically indicated, or after lesions have been identified.
Audiology
Audiometry assessment should be performed at diagnosis and repeated if hearing loss is suspected.
Screening of family members
All first degree relatives require the same annual follow ups until the disease has been genetically excluded.
Screening should start as early as age five in asymptomatic family members, as retinal lesions and phaeochromocytoma have been reported from this age.