Understanding Pheochromocytomas and Paragangliomas

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.

Anatomy and physiology of pheochromocytomas and paragangliomas

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.

1. Outer cortex vs inner medulla

To begin, each gland is divided into an outer cortex and an inner medulla, where:

• The cortex is responsible for producing cortisol, aldosterone, and sex hormones
• The medulla contains chromaffin cells that secrete stress-related catecholamines

2. Sympathetic vs parasympathetic nervous systems

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.

3. Pheochromocytomas vs paragangliomas

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.

• Pheochromocytomas primarily originate in the adrenal medulla.
• Paragangliomas are typically found along the sympathetic and parasympathetic paraganglia outside the adrenal glands.

Epidemiology and clinical presentation

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.

Symptoms

While some tumours remain asymptomatic and undetected for years, some tumours can produce symptoms due to the excess hormones, including:

• High blood pressure
• Palpitations
• Sweating
• Severe headaches.

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.

Diagnosis

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.

Genetic and molecular aspects

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.

Treatment options

There are several options for the treatment of pheochromocytomas and paragangliomas, including:

• Surgical removal for localised tumours, which can be curative or used to debulk the tumour
• Radionuclide therapy with I131 MIBG or peptide receptor radionuclide therapy (PRRT) for metastatic conditions
• Chemotherapy in some cases, though its effectiveness varies

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.

Preparation for testing

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:

1. Following specific dietary restrictions
2. Making adjustments to medication
3. Adhering to fasting requirements.

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.