Pheochromocytoma and Paraganglioma

Pheochromocytomas are catecholamine-secreting tumours of the adrenal medulla, and paragangliomas are closely related tumours arising from extra-adrenal paraganglia. Both derive from chromaffin cells and can secrete adrenaline, noradrenaline, or their precursors, producing episodic or sustained effects driven by catecholamine excess. A striking feature of this tumour group is its strong hereditary component, with a large fraction linked to germline mutations in susceptibility genes.

Definition

Pheochromocytoma is a catecholamine-producing tumour of adrenal medullary chromaffin cells, and paraganglioma is a related tumour arising from extra-adrenal sympathetic or parasympathetic paraganglia; together they form a group of chromaffin-cell neoplasms.

Scope

This entry covers the chromaffin-cell origin of pheochromocytoma and paraganglioma, the consequences of catecholamine excess, the biochemical basis of diagnosis through metabolite measurement, and the prominent role of inherited susceptibility genes. It is a reference topic and does not provide perioperative or pharmacological management instructions.

Core questions

• Does a chromaffin-cell tumour secrete catecholamines, and how is that excess detected biochemically?
• Is the tumour adrenal (pheochromocytoma) or extra-adrenal (paraganglioma), and what does its location imply?
• Does the tumour reflect an inherited susceptibility syndrome that has implications for the patient and relatives?

Key concepts

• Chromaffin cells and the adrenal medulla
• Catecholamine (adrenaline and noradrenaline) excess
• Plasma and urinary metanephrines as diagnostic markers
• Pheochromocytoma versus extra-adrenal paraganglioma
• Hereditary susceptibility genes
• Functional imaging for localisation
• Catecholamine-related cardiovascular effects

Mechanisms

These tumours secrete catecholamines and their precursors, and the resulting excess produces the cardiovascular and metabolic effects associated with sustained or episodic adrenergic stimulation. Because catecholamines are continuously metabolised to metanephrines within tumour cells, measurement of plasma or urinary metanephrines is the biochemical foundation of diagnosis, capturing ongoing tumoural metabolism more reliably than the parent catecholamines alone. Pheochromocytomas arise in the adrenal medulla, while paragangliomas arise from extra-adrenal paraganglia and can secrete differently depending on their sympathetic or parasympathetic origin. A substantial proportion of cases are associated with germline mutations in susceptibility genes, making the group a paradigm of hereditary endocrine neoplasia.

Clinical relevance

Pheochromocytoma and paraganglioma matter because unrecognised catecholamine excess can have serious cardiovascular consequences and because their strong heritability has implications extending to family members. This entry explains the diagnostic concept and the genetic dimension; it is not a basis for diagnosis or for any pharmacological or surgical management, which require specialist care.

Epidemiology

Pheochromocytomas and paragangliomas are uncommon tumours and are an infrequent but important cause of secondary hypertension. A notably large proportion, often cited as around a third or more, carry an identifiable germline susceptibility mutation, the highest hereditary fraction among human tumours, which is why genetic evaluation is emphasised in guidelines.

Evidence & guidelines

The Endocrine Society clinical practice guideline on pheochromocytoma and paraganglioma (Lenders and colleagues, 2014) sets out the framework for biochemical diagnosis, localisation, and genetic evaluation, and these tumours are also addressed within guidance on adrenal masses.

History

Chromaffin-cell tumours of the adrenal medulla were recognised and named in the early twentieth century from the chromaffin staining reaction of their cells. The later identification of catecholamine metabolites as diagnostic markers and the discovery of numerous hereditary susceptibility genes transformed understanding of the tumour group and established its place as a model of inherited endocrine cancer.

Key figures

• Jacques W. M. Lenders
• Graeme Eisenhofer

Seminal works

• lenders-2014

Frequently asked questions

What is the difference between a pheochromocytoma and a paraganglioma?

A pheochromocytoma arises in the adrenal medulla, while a paraganglioma arises from related chromaffin tissue outside the adrenal gland (extra-adrenal paraganglia). Both come from chromaffin cells and can secrete catecholamines.

Why is genetic evaluation emphasised for these tumours?

An unusually large share of pheochromocytomas and paragangliomas are linked to inherited mutations in susceptibility genes, among the highest of any tumour type, so identifying a germline cause has implications for the patient and for relatives. Genetic testing decisions are made with specialist guidance.