Pathophysiology
Summary
The adrenal medulla is primarily composed of chromaffin cells that originate from the neural crest. These cells are activated by preganglionic sympathetic fibers and release catecholamines such as norepinephrine and epinephrine. A main pathology of the adrenal medulla is pheochromocytoma, a neoplastic chromaffin cell tumor. 10% of these tumors are malignant, 10% are bilateral, and 10% are extra-adrenal, termed paragangliomas, often found near spinal sympathetic chain ganglia.
Familial pheochromocytomas are more likely to be and are associated with syndromes like multiple endocrine neoplasia Type 2 (MEN2) and Von Hippel Lindau (VHL) syndrome, both with autosomal dominant inheritance. MEN2 results from RET proto-oncogene mutations and is associated with various other endocrine tumors. VHL syndrome arises due to mutations in the VHL gene, and are also associated with paragangliomas, hemangioblastomas and renal cell carcinoma. Neurofibromatosis 1 (NF-1), another related syndrome, typically causes unilateral pheochromocytomas and arises from NF1 gene mutations. NF1 is associated with cafe au lait spots and neurofibromas
Clinically, pheochromocytomas present with episodic headaches, tachycardia, sweating, & hypertension. Morphologically, they are yellow-tan with well-defined edges, and may show signs of hemorrhage and necrosis. Microscopically, they display patterns of spindle-shaped chromaffin cells with granular cytoplasm.
Diagnosis involves measurement of urinary or plasma the catecholamine metabolites metanephrine, normetanephrine, vanillylmandelic acid can be measured. Standard treatment is surgical removal, Preoperatively, phenoxybenzamine, a non-selective alpha blocker, is often administered. Alpha blockers must be administered before beta blockers to prevent severe hypertension due to unopposed alpha-1 activity.
Neuroblastoma is the predominant adrenal medulla tumor in children, also originating from neural crest cells. Typically found in the adrenal medulla, these tumors may exhibit N-MYC oncogene amplification. Clinical symptoms include an abdominal mass, fever & weight loss, opsoclonus-myoclonus syndrome, and bone pain from metastasis in advanced cases. is another characteristic presentation. Histologically, neuroblastomas feature small blue cells forming "Homer-Wright" rosettes. Treatment often involves surgical resection and chemotherapy, depending on staging and other clinical factors.
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FAQs
Pheochromocytoma can present with a variety of symptoms such as headaches, sweating, tachycardia, and hypertension, often presenting episodically. Diagnosis is done by measuring urinary or plasma metanephrines, which are the metabolites of the catecholamines secreted by the tumor.
Pheochromocytomas are common in multiple endocrine neoplasia type 2 (MEN2) and Von Hippel Lindau (VHL) syndromes, both of which are autosomal dominant. MEN2 is caused by mutations in the RET protooncogene, while VHL is caused by mutations in the VHL tumor suppressor gene. Both syndromes are associated with multiple endocrine tumors, including pheochromocytomas and, in the case of VHL, with paragangliomas as well.
Pheochromocytomas are typically treated with surgical removal. Preoperatively, a non-selective ALPHA blocker such as phenoxybenzamine is used to minimize surgery-related morbidity. It's important to note that BETA blockers should only be administered after alpha-blockade to prevent severe hypertension due to unopposed alpha-1 activity.
Neuroblastoma, like pheochromocytoma, is most commonly a tumor of the adrenal medulla. It also arises from neural crest cells, which populate the adrenal medulla and sympathetic ganglia. However, neuroblastomas can develop anywhere along the sympathetic chain ganglia in addition to the adrenal medulla, and often contain amplification of the oncogene N-MYC. Neuroblastomas are more common in children, and display different symptoms such as abdominal pain or mass, fever, weight loss, and sometimes bone pain due to bone metastasis.
Pheochromocytomas are composed of neoplastic chromaffin cells, which appear yellow-tan with well-defined margins and nests of spindle-like cells (‘Zellballen’). Over time they can develop areas of hemorrhage, necrosis, and cyst formation. In contrast, neuroblastomas display small round blue cells organized in a specific pattern around a central space, forming ‘Homer-Wright' rosettes.
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