Paraganglioma

• Paraganglioma is a rare neuroendocrine tumor originating outside the adrenal glands.
• Symptoms vary widely depending on the tumor’s location and whether it produces hormones, often including hypertension and headaches.
• Diagnosis involves biochemical tests for hormone levels, advanced imaging, and genetic testing due to its frequent hereditary nature.
• Treatment typically includes surgery, with radiation therapy or medical management considered for unresectable or metastatic cases.
• A multidisciplinary approach is crucial for effective management of this complex condition.

What is Paraganglioma?

Paraganglioma is a rare type of tumor that arises from paraganglia, clusters of neuroendocrine cells distributed throughout the body. These tumors are closely related to pheochromocytomas, which originate specifically in the adrenal glands. Unlike pheochromocytomas, paragangliomas develop in extra-adrenal locations. They can be found in the head and neck (often non-secretory), chest, or abdomen (frequently secretory, meaning they produce hormones).

The presence of a Paraganglioma disease can significantly impact a patient’s health, particularly if the tumor secretes catecholamines such as adrenaline and noradrenaline. These hormone-secreting tumors can lead to a range of systemic effects, while non-secreting tumors primarily cause symptoms due to their mass effect on surrounding tissues.

Paraganglioma Symptoms, Causes, and Diagnosis

The manifestation of Paraganglioma symptoms and signs can vary widely, largely depending on the tumor’s location and whether it produces hormones. Functional (hormone-secreting) paragangliomas often present with symptoms related to excessive catecholamine release, while non-functional tumors may only cause symptoms when they grow large enough to compress nearby structures.

• Hypertension: Often severe and fluctuating, sometimes resistant to standard medications.
• Headaches: Typically sudden, severe, and throbbing.
• Palpitations: A sensation of a rapid or irregular heartbeat.
• Sweating: Profuse and often generalized.
• Anxiety or Panic Attacks: Sudden feelings of fear or apprehension.
• Mass Effect: For tumors in the head and neck, symptoms might include hearing loss, tinnitus, hoarseness, or difficulty swallowing.

The Causes and diagnosis of paraganglioma involve a combination of clinical evaluation, biochemical testing, and advanced imaging. Approximately 30-50% of paragangliomas are hereditary, linked to germline mutations in specific genes, most commonly those in the succinate dehydrogenase (SDH) gene family (SDHA, SDHB, SDHC, SDHD, SDHAF2). Genetic testing is therefore a crucial component of the diagnostic process, especially for younger patients or those with a family history.

Diagnosis typically begins with biochemical tests to measure catecholamines and their metabolites (metanephrines and normetanephrines) in plasma or 24-hour urine samples. Elevated levels strongly suggest a functional tumor. Imaging studies are then used to locate the tumor and assess its extent. These may include:

• Computed Tomography (CT) scans
• Magnetic Resonance Imaging (MRI)
• Nuclear medicine scans, such as MIBG (metaiodobenzylguanidine) scintigraphy or PET (positron emission tomography) scans, which can identify tumors based on their metabolic activity or specific uptake of tracers.

Paraganglioma Treatment Options

The approach to Paraganglioma treatment options explained depends on several factors, including the tumor’s location, size, whether it is functional, and if it has spread. A multidisciplinary team, often including endocrinologists, surgeons, oncologists, and genetic counselors, is essential for optimal patient care.

For localized tumors, surgical resection is generally the primary treatment. Prior to surgery for functional tumors, patients typically receive alpha-blocker medication to control blood pressure and prevent hypertensive crises during the procedure. This medical preparation is critical for patient safety. If complete surgical removal is not feasible or if the tumor is unresectable, other treatment modalities may be considered.

Radiation therapy can be used for local control, especially for head and neck paragangliomas that are difficult to remove surgically or for recurrent disease. For metastatic or advanced paragangliomas, systemic therapies such as chemotherapy, targeted therapies (e.g., tyrosine kinase inhibitors), or radionuclide therapy (e.g., 131I-MIBG therapy) may be employed to manage symptoms and slow disease progression. In some cases of small, asymptomatic, non-functional tumors, active surveillance with regular monitoring might be an appropriate strategy.