SDHB mutation carriers may develop benign or malignant phaeochromocytomas and paragangliomas, renal, gastrointestinal stromal and possibly thyroid tumours. SDHD is associated with phaeochromocytomas and paragangliomas. SDHC carriers often present with a single benign tumour only. The diagnosis requires genetic testing in all cases.
A family history may be diagnostic or suggestive of familial phaeochromocytomas, for example sudden unexpected deaths. This raises the possibility of any of the familial phaeochromocytoma syndromes such as those caused by SDHD or SDHC mutations.
However, a history of renal cell carcinoma, gastrointestinal stromal tumours or malignant extra-adrenal disease are all suggestive of SDHB. Renal and pancreatic cysts, epidydimal or broad ligament cystadenomas, and neurological problems all suggest Von Hippel Lindau. Skin and neurological lesions suggest neurofibromatosis, or the patient may have had positive genetic screening or a known family history of an SDH mutation.
Intermittent or severe hypertension in a young person demands investigation for possible phaeochromocytoma.
Although typically this occurs in acute attacks, some patients with phaeochromocytoma describe a more generalised increase in anxiety.
Typical attacks include rapid regular palpitations.
Patients with phaeochromocytoma may present with an apparent 'acute abdomen'.
Abdominal pain could also be due to complications of renal tumours and requires thorough investigation on its own merits.
Anorexia and weight loss are alarm symptoms for possible malignant disease.
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.
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.
Phaeochromocytoma attacks ten to be of sudden onset and stop suddenly, whereas anxiety attacks may build and tend to be triggered by circumstances.
Phaeochromocytoma attacks tend to start and stop abruptly. Epileptic seizures may be followed by a headache or exhaustion.
Typically the patient will look pale and may be clammy. Flushing or redness implies an alternative cause, for example menopausal flushing or carcinoid syndrome.
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.
Untreated obstructive sleep apnoea leads to chronic elevation of catecholamines and so false positive biochemical screening tests. Assess using Epworth sleepiness score.
Almost all antidepressants may lead to false positive urine metanephrine results.
Renal cancer is associated with phaeochromocytoma in patients carrying SDHB or Von Hippel Lindau mutations.
Epididymal and broad ligament cystadenomas are also associated with VHL.
Pituitary tumours have also been described in patients with SDHB mutations. Other visual or neurological problems suggest an alternative diagnosis such as VHL.