Pheochromocytomas (pheos) and paragangliomas (paras) are rare neuroendocrine tumours (NETs) that arise from chromaffin cells, primarily found in the adrenal glands and the paraganglia of the sympathetic and parasympathetic nervous systems.
These tumours are noteworthy for their ability to produce excessive catecholamines, such as adrenaline and noradrenaline, which can significantly disrupt normal physiological processes.
The human adrenal glands, located atop the kidneys, are crucial for hormone production and stress response. There are several important steps in order to make distinctions between pheochromocytomas and paragangliomas.
To begin, each gland is divided into an outer cortex and an inner medulla, where:
The sympathetic nervous system facilitates the “fight or flight” response, impacting heart rate, blood pressure, and energy mobilisation.
On the other hand, the parasympathetic nervous system helps to conserve energy and restore calm by slowing the heart rate and increasing intestinal and gland activity.
The location of these tumours dictates whether they are likely to produce hormones, with sympathetic paragangliomas typically being hormonally active and parasympathetic ones generally not.
The incidence of pheochromocytomas is estimated at 1–4 cases per million people per year. They can affect all ages but have a peak incidence in adults between 40 and 50 years, although about 20% of cases occur in children and adolescents.
While some tumours remain asymptomatic and undetected for years, some tumours can produce symptoms due to the excess hormones, including:
Paragangliomas, while similar to pheochromocytomas, can also be located in regions such as the head, neck, thorax, abdomen, and pelvis.
Depending on their location and genetic makeup, these tumours may secrete hormones that lead to symptomatic high blood pressure and other related symptoms.
The diagnosis of pheochromocytomas and paragangliomas involves a combination of biochemical tests and imaging studies. The most accurate biochemical test is the measurement of plasma free metanephrines.
Alternatively, 24-hour urine fractionated metanephrines can be used. To avoid false positives due to postural changes, the collection of blood samples must be done under specific conditions, such as after fasting and lying down.
Over the last decade, there has been a significant advancement in understanding the genetic basis of these tumours. More than 30% of patients have hereditary forms of the disease, with mutations in specific genes like SDHB being particularly important for predicting the risk of malignant disease. Genetic testing is recommended for patients and their families to guide management and surveillance strategies.
There are several options for the treatment of pheochromocytomas and paragangliomas, including:
Advances in targeted molecular therapies have also shown promise, particularly therapies targeting specific genetic mutations associated with these tumours. Mutations targeted can be familiar germline, or somatic in presentation.
Due to the complexity of these tumours and the sensitivity of diagnostic tests, it is crucial for patients to prepare adequately before testing. This includes:
Stress from exercise or caffeine can affect the results, so patients are often advised to avoid these before testing.
Pheochromocytomas and paragangliomas are complex diseases with significant implications for patients undergoing treatment. The effective management of these conditions involves a comprehensive approach that includes accurate diagnosis, understanding of the genetic background, and application of appropriate treatments. Continued research and development in genetic understanding and treatment modalities hold promise for improving outcomes for patients with these rare tumours.
Further information and support for people diagnosed with pheochromocytomas and paragangliomas is available by calling the NECA NET nurse line.
