Phaeochromocytoma - Adrenal axis

Phaeochromocytoma

Definition

An APUD (amine precursor uptake and decarboxyla-tion) tumour of the adrenal medulla which produces adrenaline and noradrenaline.

Incidence

Uncommon. The cause of 0.2–0.5% of cases of adult hypertension.

Age

Peak age 40–60 years.

Sex

M = F

Aetiology

Associated with the Multiple Endocrine Neoplasia (MEN) type II. Also may be associated with von Hippel-Lindau syndrome, neurofibromatosis, tuberose sclerosis and the Sturge-Weber syndrome.

Pathophysiology

10% of cases are malignant, 10% are extraadrenal and 10% are bilateral. The adrenal medulla is functionally related to the sympathetic nervous system, secreting adrenaline and noradrenaline in response to sympathetic stimulation. High levels of sympathetic stimulation result in increased heart rate, blood pressure, and sweating. There is decreased blood supply to the gut, increased sphincter activity and metabolic effects, such as diabetes and thyrotoxicosis.

Clinical features

Patients normally present with episodic headache, sweating, and palpitations. They are found to be hypertensive which may be paroxysmal or continuous. Other signs include pallor, dilated pupils and tachycardia. There may be a postural hypotension secondary to volume depletion. Phaeochromocytoma may present in pregnancy, or with sudden death following trauma or surgery.

Macroscopy

Usually up to 5 cm spherical tumour with a pale cut surface that oxidises to brown when exposed to air. Extramedullary tumours are usually found in the sympathetic chain, alongside the abdominal aorta.

Complications

Cardiovascular disease or cerebral haemorrhage. Persistent hypertension causes hypertensive retinopathy.

Investigations

Diagnosis is by measuring plasma levels of noradrenaline, and urinary adrenaline and noradrenaline or their metabolites vanillylmandelic acid (VMA) and homovanilyic acid (HVA). The paroxysmal secretion of the hormones may mean repeated measurements are needed. Adrenal CT scan is used to locate the tumour, scanning with a radiolabelled catecholamine precursor (MIBG) can identify extraadrenal tumours.

Management

Surgical excision where possible is the treatment of choice. Surgery has a high perioperative risk and requires expert anaesthetic supervision. The blood pressure must be carefully monitored and any rise countered with i.v. phentolamine (α-receptor antagonist) or nitroprusside. Intensive care postoperatively is preferred.

Adrenergic blockade is necessary to oppose the catecholamine effects before surgery. Phenoxybenzamine (an Î±-receptor antagonist) is used initially, followed by Î²-blockade with propanolol.

In cases where surgery is not possible combined long term Î±- and Î²-blockers are used.

Prognosis

10% of phaechromocytomas are malignant these have a 5 year survival of less than 50%. Overall recurrence rate of 10–15%.