Disorders Of The Adrenal Medulla
Phaeochromocytoma and paraganglioma
Phaeochromocytomas are catecholamine-secreting tumours which occur in about 0.1% of patients with hypertension. In about 90% of cases they arise from the adrenal medulla. The remaining 10%, which arise from extra-adrenal chromaffin tissue, are termed paragangliomas (Figure 22.1).
Most phaeochromocytomas are sporadic but a genetic basis is recognised in up to 30% of patients (Table 22.1), especially in bilateral, extra-adrenal or malignant tumours (<10%).
Symptoms and signs
Common presenting symptoms include one or more of headache, sweating, pallor and palpitations. Less commonly, patients describe anxiety, panic attacks and pyrexia. Hypertension, whether sustained or episodic, is present in at least 90% of patients. Left untreated, phaeochromocytomas can occasionally lead to hypertensive crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias or even death. Patients with undiagnosed phaeochromocytomas having routine surgery can develop severe hypertension or sudden death.
Diagnosis relies on the biochemical confirmation of elevated catecholamines or their metabolites (metanephrines), followed by radiological localisation of the tumour.
The biochemical screening investigation of choice is usually 24-hour urinary fractionated metanephrines with or without free catecholamines. Two or more collections may be needed if the index of suspicion is high because of the episodic nature of tumour secretion. Measurement of plasma metanephrines has replaced urine collection in many centres, and is especially useful if measured during symptoms or crisis. Serum chromogranin A levels, a marker of neuro-endocrine hypersecretion, can be elevated in phaeochromocytoma or paraganglioma.
CT (Figure 22.2) or MRI of the abdomen are the initial imaging modalities of choice, followed by whole-body MRI if the tumour is not localised. 123I-meta-iodobenzylguanidine (MIBG) can locate tumours not seen on MRI and is useful pre-operatively to exclude multiple tumours (Figure 22.3).
Genetic testing is indicated in patients with syndromic presentations but also in many apparently sporadic tumours, because up to 30% harbour germline mutations in susceptibility genes. Mutations are more likely in patients presenting at a young age, or in those with multifocal, malignant or extra-adrenal disease. Identification of a predisposing mutation should lead to annual screening for new or recurrent disease in index cases, and cascade genetic testing of first degree relatives.
The definitive treatment is surgical excision, which is performed laparoscopically or through an open procedure. In advance of surgery, it is mandatory that all patients are protected from the effects of catecholamine excess by pharmacological alpha with or without beta-blockade. Alpha-blockade, conventionally administered as oral phenoxybenzamine, should be commenced before beta-blockade in order to avoid unopposed alpha-adrenergic stimulation and the risk of hypertensive crisis. Beta-blockers can be introduced subsequently to control reflex tachycardia.
Five-year survival for apparently benign tumours is 96% and the recurrence rate is less than 10%. Successful surgical removal leads to cure of hypertension in most patients. Malignant disease can be treated with 131-I MIBG therapy or chemotherapy. There is increasing interest in the use of newer radionuclides in both the diagnosis and treatment of metastatic disease.