Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that develop from chromaffin cells. These tumors produce and release excessive amounts of hormones, primarily catecholamines. Understanding these tumors is important for accurate diagnosis and effective management.
Understanding Pheochromocytoma and Paraganglioma
Pheochromocytomas originate within the adrenal glands, which are small glands located on top of each kidney. More precisely, they arise from chromaffin cells in the adrenal medulla, the inner part of the adrenal gland. Paragangliomas develop from similar chromaffin cells but are located outside the adrenal glands. These extra-adrenal tumors can form in various nerve ganglia throughout the body, including the neck, chest, abdomen, and pelvis.
Both types of tumors produce catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. These hormones regulate the body’s “fight or flight” response, influencing heart rate, blood pressure, and metabolism. The overproduction of these hormones leads to a variety of symptoms. These tumors are rare, affecting an estimated 2 to 8 people per million per year.
Recognizing the Signs
Excess catecholamines from pheochromocytomas and paragangliomas often lead to a distinct set of symptoms. A classic presentation includes headaches, profuse sweating (diaphoresis), and rapid heartbeats (palpitations or tachycardia). These symptoms can occur suddenly and intensely, often described as “spells”.
High blood pressure (hypertension) is a common and significant sign, frequently presenting as severe, sustained, or episodic elevations. Other symptoms include anxiety, sometimes mimicking panic attacks, tremors, and pallor. Patients may also experience abdominal pain, nausea, vomiting, unexplained weight loss, and difficulty controlling blood sugar levels, leading to glucose intolerance.
Symptom attacks can be triggered by factors like physical exertion, stress, or changes in body position. Certain foods containing tyramine, like red wine or chocolate, and some medications can also precipitate these episodes. The episodic nature of these symptoms, with periods of feeling well between “spells,” can make diagnosis challenging as they can mimic other conditions.
Diagnosis and Management
Diagnosing pheochromocytoma and paraganglioma involves biochemical and imaging tests. Biochemical tests detect excess hormone production, commonly using a 24-hour urine collection for fractionated metanephrines and catecholamines, or a blood test for plasma free metanephrines.
Once biochemical evidence suggests a tumor, imaging studies pinpoint its location. Computed tomography (CT) scans or magnetic resonance imaging (MRI) of the abdomen and pelvis frequently visualize the adrenal glands and surrounding areas. For more precise localization, especially for extra-adrenal tumors or to detect metastatic spread, functional imaging techniques are utilized. These include MIBG scintigraphy (Iobenguane scan) or Positron Emission Tomography (PET) scans using specific tracers like 18F-FDG, 18F-DOPA, or 68Ga-DOTATATE.
Surgical removal of the tumor is the primary and most effective treatment. For pheochromocytomas, a laparoscopic adrenalectomy is often performed. Before surgery, patients undergo crucial pre-operative preparation, typically involving alpha-blockade medications such as phenoxybenzamine or doxazosin, to control blood pressure and prevent hypertensive crises during surgery. Beta-blockers may also be added after adequate alpha-blockade to manage heart rate. For tumors that are metastatic or cannot be surgically removed, other treatment options may include targeted radiation therapy, chemotherapy, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, or high-dose 131I-MIBG therapy.
Genetic Links and Long-Term Outlook
A significant proportion of pheochromocytomas and paragangliomas, approximately 35% to 40%, are linked to hereditary genetic mutations. These tumors can run in families, with specific gene alterations increasing an individual’s predisposition. Several genetic syndromes are associated with an elevated risk, including Multiple Endocrine Neoplasia type 2 (MEN2), Von Hippel-Lindau (VHL) disease, Neurofibromatosis type 1 (NF1), and mutations in the Succinate Dehydrogenase (SDH) genes (SDHA, SDHB, SDHC, SDHD, SDHAF2).
Genetic testing is often recommended for patients diagnosed with these tumors, and sometimes for their family members, particularly if a hereditary syndrome is suspected. This testing can aid in early detection and screening for other associated conditions in affected individuals and at-risk relatives.
Most pheochromocytomas and paragangliomas are benign. However, a subset, especially paragangliomas and those with certain genetic mutations like SDHB, have a higher potential for malignancy and metastatic spread to distant sites such as lymph nodes, liver, lungs, and bone.
The prognosis after successful surgical removal is generally favorable, but lifelong follow-up is necessary due to the risk of recurrence or new tumors. Even for benign cases, continued monitoring with regular biochemical tests and imaging is recommended to detect any signs of disease return. This ongoing surveillance helps ensure long-term well-being and allows for prompt intervention if new tumors arise.