61. Disturbances of the adrenal medulla and the sympathetic system – pheochromocytoma

The most important disorders of the adrenal medulla are neoplasms, and the most important neoplasm is phaeochromocytoma.

Phaeochromocytoma

A phaeochromocytoma is a catecholamine-secreting tumor located in the adrenal medulla. It originates from the chromaffin cell which can produce catecholamines. This tumor is famous for following the “rules of ten”:

• 10% of cases of pheochromocytoma occur bilaterally (90% occur unilaterally)
• 10% of cases are familiar (90% are sporadic) – as part of genetic syndromes
• 10% of cases are malignant (90% are benign)
• 10% of cases are extra-adrenal, often in sympathetic ganglia (90% are in the adrenal medulla)
• 10% of cases occur in children (90% occur in adults)

Extra-adrenal phaeochromocytoma is also called paraganglioma and can be located anywhere where there is sympathetic nervous system. Common places involve around the big vessels and in the abdominal cavity.

In the majority of cases the tumor produces catecholamines in episodes rather than continuously.

Etiology

Most cases are sporadic, but phaeochromocytomas can also be hereditary and associated with:

• Multiple endocrine neoplasia type 2A and 2B
• Neurofibromatosis type 1
• Von Hippel-Lindau disease

Pathophysiology

Phaeochromocytomas secrete predominantly noradrenaline. This changes the noradrenaline:adrenaline ratio from the normal 1:5 to around 1:1. Noradrenaline acts more on alpha-receptors than adrenaline does. Alpha-receptors are the adrenergic receptors that cause vasoconstriction, which is why this tumor causes significant hypertension. Systolic pressure of even 300 mmHg can occur; the diastolic also increases but not as much.

The tumor most frequently releases catecholamines in episodes rather than continuously. These episodes often occur at random, but they can be triggered by physical exercise, Valsalva manoeuvre, and drugs.

Clinical features

• Episodes of:
  • Hypertensive crisis
  • Throbbing headache
  • Excessive sweating
  • Palpitations
  • Tachycardia
  • Pallor
  • Anxiety
• Persistent hypertension (less frequent)

The episodes can occur multiple times a day or with months in between, and they can last for seconds to hours. They tend to get worse as the tumor grows.

Complications

The complications are mostly related to the hypertensive crisis that may occur.

• Ischaemic or haemorrhagic stroke
  • Rupture of berry aneurysms
• Myocardial infarction
• Aortic dissection
• Hypertensive encephalopathy
• Pulmonary oedema
• Arrhythmias

Diagnosis

Metanephrines are breakdown-products of catecholamines that are excreted with urine. Most phaeochromocytomas continuously leak metanephrines and so diagnosis can be made even in the absence of an episode.

The best initial test is to test for metanephrines in the plasma, but to confirm the diagnosis a 24-hour urine collection should be obtained and the level of metanephrines and catecholamines should be measured.

Testing for vanillylmandelic acid (VMA), another breakdown product of catecholamines is mentioned in the book but is no longer preferred. This metabolite has a higher false-positive rate than metanephrine.

Treatment

Removal of the tumor is curative. Before the surgery, alpha-blockers like phenoxybenzamine should be given to prevent a hypertensive crisis during the surgery. Physically touching the tumor may trigger catecholamine release and so the tumor is often removed with the “no-touch” technique.

Hypofunction of the adrenal medulla

The most important clinical entity characterised by hypofunction of the adrenal medulla is idiopathic orthostatic hypotension. The name explains the condition, which is assumed to be associated with damage to the CNS. The adrenal medulla doesn’t respond to the orthostatic position correctly, causing orthostatic hypotension.

Some rare cases of hypoglycaemia in children may be attributed to a low secretion of catecholamines in response to hypoglycaemia. This is called “adrenal medullary unresponsiveness”.