Pheochromocytoma Tutorial Notes

Pheochromocytom a Etiology Pheochromocytomas arise from chromaffin cells, which are neuroendocrine cells derived from the neural crest. While most pheochromocytomas occur sporadically, approximately 1020% are associated with hereditary syndromes such as multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau (VHL) disease, neurofibromatosis type 1 (NF1), or familial paraganglioma syndromes. Genetic mutations in genes such as RET, VHL, NF1, SDHx, and MAX have been implicated in the development of hereditary pheochromocytomas. Clinical Features 1. Hypertension: The hallmark feature of pheochromocytoma is hypertension, which can be paroxysmal or sustained. Hypertensive crises are often characterized by severe, episodic elevations in blood pressure, accompanied by symptoms such as headache, palpitations, sweating, and anxiety. 2. Palpitations and Tachycardia: Pheochromocytoma-induced catecholamine release can cause palpitations, tachycardia, and arrhythmias due to adrenergic stimulation of the heart. Patients may experience sensations of rapid or irregular heartbeat, chest discomfort, or syncope during hypertensive episodes. 3. Diaphoresis: Excessive sweating (diaphoresis) is a common symptom of pheochromocytoma, particularly during hypertensive crises. Profuse sweating may occur suddenly and be accompanied by feelings of warmth, flushing, or anxiety. 4. Headache and Pallor: Patients with pheochromocytoma may experience severe headaches, often described as throbbing or pulsatile, during hypertensive crises. Pallor, or paleness of the skin, may also be observed due to peripheral vasoconstriction and reduced blood flow to the skin. 5. Other Symptoms: Additional symptoms of pheochromocytoma may include nausea, vomiting, abdominal pain, weight loss, tremor, visual disturbances, and psychological symptoms such as anxiety, panic attacks, or depression. Diagnosis 1. Biochemical Testing: Diagnosis of pheochromocytoma begins with biochemical testing to measure levels of catecholamines (epinephrine, norepinephrine) and their metabolites (metanephrines) in plasma or urine during baseline and provocative testing. Elevated levels of catecholamines or metanephrines support the diagnosis of pheochromocytoma. 2. Imaging Studies: Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), or metaiodobenzylguanidine (MIBG) scintigraphy are used to localize pheochromocytomas, assess tumor size, and evaluate for metastatic disease. CT or MRI of the abdomen is the preferred initial imaging modality. 3. Genetic Testing: Patients with suspected pheochromocytoma may undergo genetic testing to identify underlying hereditary syndromes associated with the tumor. Genetic testing can help guide management and screening recommendations for patients and their family members. Management 1. Alpha-Blockade: Pharmacological management of pheochromocytoma typically begins with alpha-adrenergic blockade using medications such as phenoxybenzamine or doxazosin to control hypertension and prevent hypertensive crises. Alpha-blockade should be initiated before beta-blockade to prevent unopposed alpha-adrenergic stimulation. 2. Beta-Blockade: Beta-adrenergic blockade with medications such as propranolol or metoprolol may be added to control tachycardia and palpitations once alpha-blockade has been established. Beta-blockade is usually initiated after adequate alpha-blockade to prevent exacerbation of hypertension. 3. Surgical Resection: The definitive treatment for pheochromocytoma is surgical resection of the tumor. Preoperative alpha-blockade and volume expansion are essential to minimize the risk of intraoperative hypertensive crisis and hemodynamic instability. Laparoscopic adrenalectomy is the preferred approach for most adrenal pheochromocytomas. 4. Follow-up and Surveillance: Patients with pheochromocytoma require long-term follow-up and surveillance to monitor for recurrence, metastasis, and associated hereditary syndromes. Regular biochemical testing and imaging studies may be performed to assess tumor markers, evaluate adrenal function, and detect recurrent or metastatic disease. Prognosis The prognosis for patients with pheochromocytoma is generally favorable with early detection, appropriate management, and surgical resection of the tumor. The majority of pheochromocytomas are benign, and surgical resection can lead to complete resolution of symptoms and normalization of blood pressure. However, delayed diagnosis or inadequate management can result in severe complications such as hypertensive crisis, myocardial infarction, stroke, or death. Patients with hereditary syndromes associated with pheochromocytoma may require lifelong surveillance for recurrent or metastatic disease. With prompt diagnosis, multidisciplinary management, and comprehensive follow-up, most patients with pheochromocytoma can achieve good outcomes and long-term survival.