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.

Is there any relevant family or personal history? 

A family history may be suggestive of familial phaeochromocytoma, for example of sudden unexpected deaths, or diagnostic of VHL if haemangiomas, renal cancer and phaeochromocytomas are reported.

Renal and pancreatic cysts, and epididymal and broad ligament cystadenomas also occur in VHL.

Have they ever been found to have high blood pressure? 

Intermittent or severe hypertension in a young person demands investigation for possible phaeochromocytoma.

Do they complain of generalised anxiety or fear? 

Although typically this occurs in acute attacks, some patients with phaeochromocytoma describe a more generalised increase in anxiety.

Do they complain of palpitations? 

Typical attacks include rapid regular palpitations.

Do they complain of abdominal pain or other abdominal symptoms? 

Patients with phaeochromocytoma may present with an apparent 'acute abdomen'. However, in VHL, renal and pancreatic cysts and renal cell carcinoma are also common and so any suspicious abdominal symptoms should be thoroughly investigated.

Has there been any change in appetite or weight or other features suggesting malignancy? 

Anorexia and weight loss are alarm symptoms for possible malignant disease.

Take a detailed history of their attacks

Ask the patient to describe exactly what happens.

Typically people with a phaeochromocytoma will describe episodes of sudden intense fear, with palpitations, anxiety, looking pale and clammy and sometimes collapsing.

Are there any triggers to the attacks? 

Precipitants may suggest an alternative cause. For example, if they occur after fasting they may be due to hypoglycaemia; postural attacks may be due to orthostatic hypotension of any cause; and, sleep deprivation may trigger epileptiform attacks.  

Phaeochromocytoma attacks tend to occur at any time although specific triggers may provide a clue to the anatomical location of an extra-adrenal lesion, for example attacks following micturition occur with bladder paragangliomas.

Is the onset and end of an attack sudden? 

Phaeochromocytoma attacks tend to be of sudden onset and stop suddenly, whereas anxiety attacks may build and tend to be triggered by circumstances.

What happens at the end of an attack? 

Phaeochromocytoma attacks tend to start and stop abruptly. Epileptic seizures may be followed by a headache or exhaustion.

Do they look pale or flushed during an attack? 

Typically the patient will look pale and may be clammy. Flushing or redness implies an alternative cause, for example menopausal flushing or carcinoid syndrome.

Are there any other associated features? 

Breathlessness, wheeze or diarrhoea may indicate an alternative pathology, for example carcinoid syndrome, incontinence may suggest epilepsy, the immediate need to pass urning may suggest a supraventricular tachycardia.

Do they have any symptoms suggestive of snoring or sleep apnoea? 

Untreated obstructive sleep apnoea leads to chronic elevation of catecholamines and so false positive biochemical screening tests. Assess using Epworth sleepiness score.

Are they taking any prescribed or non prescribed medications? 

Almost all antidepressants may lead to false positive urine metanephrine results.

Are there any features suggestive of hypercalcaemia? 

Nocturia, thirst, renal colic, depression, constipation, or depression may be symptoms of hypercalcaemia which may occur with associated malignancy.

Are there any features to suggest renal or gonadal tumours: haematuria, flank or pelvic pain, or polycythaemia? 

Renal cancer is strongly associated with phaeochromocytoma in patients carrying VHL mutations. Epididymal and broad ligament cystadenomas are also associated with VHL.

Are there any features to suggest neurological or retinal disease, for example headache, loss of balance,  or visual disturbance? 

As well as phaeochromocytomas, various neurological problems may occur in VHL. Retinal haemangioblastomas may lead to visual loss and haemangioblastomas may arise anywhere within the central nervous system typically affecting the posterior fossa leading to poor co-ordination.