The inherited mutation is found in paragangliomas more frequently than any other cancer type(1).
Nearly 35% of paragangliomas are familial in origin with 20 known susceptibility genes(2).
Are Paragangliomas Hereditary?
Paragangliomas are rare tumors, which are mostly found sporadically. However, 35% of these tumors have a familial origin and are associated with 20 known susceptibility genes, which make them strongly hereditary when compared to all other tumors(2).
Out of the 20 known susceptibility genes, three genes for three well-known cancer susceptibility syndromes include NF1 for Neurofibromatosis Type 1 (NF1), VHL for von Hippel-Lindau disease (vHL) and RET for Multiple Endocrine Neoplasia Type 2 (MEN 2). Other known susceptibility genes include those from a germline mutation in Succinate dehydrogenase (SDH) complex subunit type A (SDHA), type B (SDHB), type C (SDHC), type D (SDHD), SDH complex cofactor (SDHAF2), fumarate hydratase (FH), malate dehydrogenase type 2 (MDH2), endothelial pas domain protein 1 (EPAS1) or hypoxia-inducible factor type 2A (HIF2A), transmembrane protein (TMEM127), and myc-associated factor X (MAX). All these mutations are mostly autosomal dominant(1),(2).
Lifestyle Changes For Paragangliomas
Since sympathetic paragangliomas are catecholamine producing tumors, which are produced in episodes, so the symptoms are also experienced in episodes or spells. Certain foods and beverages containing tyramine, such as beers, wines, and certain cheeses should be avoided as they may precipitate the attack. There are certain drugs, such as histamine, glucagon, tyramine, metoclopramide, phenothiazine, adrenocorticotropic hormone, which may also increase the likelihood of these attacks. Therefore, it is best to avoid medications containing these ingredients(2).
Some groups of patients may experience postural hypotension, so these patients should avoid abrupt standing from a sitting position and should immediately sit if they experience postural hypotension to avoid a fall. Extreme physical activity should also be avoided since spells may be triggered after exertion. Patients should eat a well-balanced diet to prevent unwanted weight loss(2).
The surgical resection of benign tumors has an excellent prognosis and patients go on to live a disease-free life. However, some patients may suffer from immediate post-operative hypotension and hypoglycemia. Hypotension can be cured by fluids and upright posture of sitting; whereas, hypoglycemia is prevented by dextrose infusion. They subside after a few days post-surgery. Patients can go on to live a normal life with proper diet and activity(2).
Paragangliomas are rare tumors of chromaffin cells paraganglia along with the autonomic nervous system that is found outside the adrenal glands. These neuroendocrine tumors inside the adrenal medulla are termed as pheochromocytomas. They are found in around 2-8 per million persons/year. These tumors are either derived from sympathetic tissue in the chest, abdominal and pelvic area or the parasympathetic tissue in the head and neck and thorax region. Tumors of the sympathetic origin produce catecholamines (epinephrine, norepinephrine, dopamine) while tumors of the parasympathetic origin do not produce epinephrine(1),(2).
Clinical Presentation Of Paragangliomas
The various signs and symptoms of paragangliomas are due to the increased secretion of catecholamines by these tumors. The common presenting symptoms include headache, palpitations, excessive sweating, paroxysmal/prolonged hypertension, anxiety, nervousness, weakness, nausea, vomiting, shortness of breath, panic attacks, unwanted weight loss, tremulousness, visual problems and fatigue during an attack, abdominal pain, fever, constipation, sepsis, hypotension, acute myocardial infarction, arrhythmias, pulmonary edema, shock, and heart failure.
The difference in symptoms of the patients may be due to different catecholamines (epinephrine, norepinephrine, and dopamine) along with other neuropeptides (vasoactive intestinal peptide, atrial natriuretic factor, corticotrophin, somatostatin, calcitonin, neuropeptides Y, and parathyroid hormone-related peptide) secreted by the tumor(2).
Biochemical Testing For Paragangliomas
Biochemical testing forms the basis of initial screening for paragangliomas, which includes measurement of plasma free metanephrines and/or urinary fractioned metanephrines and catecholamines. The biochemical profile depends on the location of the tumor, such as parasympathetic tumors of the head and neck (associated with SDHC, SDHD, SDHAF2 mutations) do not produce catecholamines, so their biochemical testing will be negative for catecholamines, if they show high amounts of catecholamines then imaging studies should be done to locate another tumor. SDHB mutated tumors will produce excessive amounts of normetanephrine and also methoxytyramine (O-methylated metabolite of dopamine)(1).