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.
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.
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.
Usual treatment starts with phenoxybenzamine. This may be started at a low dose eg 10mg daily, and should be gradually uptitrated to a usual maximum of 40-60mg in divided doses daily. Close BP monitoring is required and patients must be advised to keep up a high fluid intake.
This may have unpleasant side effects, for example dizziness, malaise and swollen ankles.
Doxazosin, usually in a sustained release preparation, may be used if phenoxybenzamine is unavailable or not tolerated. Dose should be titrated to the maximum tolerated.
Once a date is set for surgery, the dose of phenoxybenzamine should be uptitrated further until the patient develops significant hypotension and nasal congestion. This may require hospital admission, intravenous fluids or even blood transfusion for haemodilution and postural hypotension.
Once a patient is fully alpha blocked, typically after about several weeks in an out patient setting, initiate beta blockade, for example with propranolol if they develop significant and symptomatic tachycardia.
This is not always necessary and must only be given after the patient is fully alpha blocked. Close BP monitoring is again required and the dose should be increased to the maximum tolerated or 240mg in divided doses.
Ideally patients will have been fully alpha and beta blocked over a period of at least six weeks prior to surgery.
Ideally, patients should be admitted preoperatively 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.
Monitor postural blood pressure and haemoglobin over successive days.
Patients frequently require intravenous fluid support for dramatic falls in blood pressure. Full blood count should be checked daily, as a dramatic fall in haemoglobin may occur, which should be treated with pre operative blood transfusions if necessary. This occurs 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.
If iv phenoxybenzamine is unavailable, the patient will require uptitration of their oral phenoxybenzamine in the week prior to surgery. This may also require admission and the dose should be increased by 10mg every 24hours until significant hypotension and nasal stuffiness occur. Patients may require intravenous fluid support as above, and ALL patients should start on iv fluids overnight before planned surgery to minimise the chance of significant perioperative hypotension.
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.
All medication may be stopped routinely.
Blood pressure should be closely monitored.
Arrange for urinary metanephrines to be repeated at six to 12 weeks.
Counselling and screening of patients and family members for phaeochromocytomas, neurological, retinal, renal, pancreatic and epididymal and broad ligament tumours must be discussed.
At diagnosis, perform an MRI of the whole brain, spinal cord and abdomen and arrange audiological and ophthalmoligical reviews.
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.
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.
Audiometry assessment should be performed at diagnosis and repeated if hearing loss is suspected.
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.