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{{short description|Type of neuroendocrine tumor}}{{Multiple issues|{{MOS|date=August 2020}}{{More medical citations needed|date=August 2020}}}}

factoids

| deaths =| alt =ËŒiːˌrmsɪtmURL-STATUS=DEAD TITLE=PHAEOCHROMOCYTOMA | MEANING & DEFINITION FOR UK ENGLISH DATE=, 2022-08-24, (fee-oh-kroh-moh-sahy-toh-muh)}}Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes.JOURNAL, Lenders JW, Eisenhofer G, Mannelli M, Pacak K, 208788653, Phaeochromocytoma, Lancet, 366, 9486, 665–75, 20–26 August 2005, 16112304, 10.1016/S0140-6736(05)67139-5, When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred to as a paraganglioma.BOOK, What is the difference between pheochromocytoma and paraganglioma? What are the familial syndromes that have pheochromocytoma as a component? What are the pathologic features of pheochromocytoma indicating malignancy?, 2008, Questions in Daily Urologic Practice: Updates for Urologists and Diagnostic Pathologists, 280–284, Oyasu R, Yang XJ, Yoshida O, Tokyo, Springer Japan, 10.1007/978-4-431-72819-1_49, 978-4-431-72819-1, Questions in Daily Urologic Practice, These neuroendocrine tumors typically release massive amounts of catecholamines which result in the most common symptoms, including hypertension (high blood pressure), tachycardia (fast heart rate), and sweating.JOURNAL, Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G, 6, Biochemical diagnosis of pheochromocytoma: which test is best?, JAMA, 287, 11, 1427–34, March 2002, 11903030, 10.1001/jama.287.11.1427, free, JOURNAL, 2001-08-22, Internal Medicine,dx.doi.org/10.1001/jama.286.8.971-jbk0822-2-1, JAMA, 286, 8, 971, 10.1001/jama.286.8.971-jbk0822-2-1, 0098-7484, Rarely, some tumors (especially paragangliomas) may secrete little to no catecholamines, making diagnosis difficult. While tumors of the head and neck are parasympathetic, their sympathetic counterparts are predominantly located in the abdomen and pelvis, particularly concentrated at the organ of Zuckerkandl.BOOK, Kellerman RD, Rakel D, Conn’s Current Therapy, 2020, Elsevier–Health Science, 1145315791, 978-0-323-79006-2,

Etymology

1920s: from phaeochrome (another term for chromaffin), from Greek phaios ‘dusky’ + khrōma ‘color’, + -cyte.

Signs and symptoms

The symptoms of a pheochromocytoma are related to sympathetic nervous system hyperactivity.JOURNAL, Tevosian SG, Ghayee HK, Pheochromocytomas and Paragangliomas, Endocrinology and Metabolism Clinics of North America, 48, 4, 727–750, December 2019, 31655773, 10.1016/j.ecl.2019.08.006, 204947638, The classic triad includes headaches (likely related to elevated blood pressure, or hypertension), tachycardia/elevated heart rate, and diaphoresis (excessive sweating, particularly at night, also known as hyperhidrosis). However, patients are unlikely to experience continuous symptoms. Due to the paroxysmal nature of catecholamine synthesis and release, patients may experience “attacks” or “spells” where they are suddenly overwhelmed with signs and symptoms of their tumor.JOURNAL, Zuber SM, Kantorovich V, Pacak K, Hypertension in pheochromocytoma: characteristics and treatment, Endocrinology and Metabolism Clinics of North America, 40, 2, 295–311, vii, June 2011, 21565668, 3094542, 10.1016/j.ecl.2011.02.002, Attacks can occur spontaneously (without warning) or may be triggered by a variety of pharmaceutical agents (including histamine, metoclopramide, glucagonJOURNAL, Hosseinnezhad A, Black RM, Aeddula NR, Adhikari D, Trivedi N, 2011, Glucagon-induced pheochromocytoma crisis, Endocrine Practice, 17, 3, e51-4, 10.4158/EP10388.CR, 21324811, and adrenocorticotropic hormone), foods that contain tyramine (cheese and wine), intraoperative tumor manipulation, intubation, or during anesthetic induction.JOURNAL, Manger WM, August 2006, An overview of pheochromocytoma: history, current concepts, vagaries, and diagnostic challenges, Annals of the New York Academy of Sciences, 1073, 1, 1–20, 2006NYASA1073....1M, 10.1196/annals.1353.001, 17102067, 21423113, File:201405 adrenal medulla.png|thumb|alt=|180x180px|Adrenal gland; the medulla (center, red) is the origin of the pheochromocytoma.]](File:Gray1120-adrenal glands.png|thumb|There is an adrenal gland, highlighted in yellow, on top of each of the kidneys.)Other clinical manifestations that have been reported include (in no particular order):

• Pallor
• Heat intolerance
• Weight loss
• Chest and/or abdominal discomfort
• Palpitations
• Nausea/vomiting
• Constipation
• Orthostatic hypotension – becoming light-headed or dizzy after swiftly changing positions
• Psychiatric manifestations
  • Anxiety, panic attacks, nervousness, tremors
• Hyperglycemia (high blood sugar)

Complications

While the symptoms of a pheochromocytoma are quite common, the disease has been referred to as “the great mimic”.{{psc|reason=Single case report|date=September 2020}} JOURNAL, Mitchell L, Bellis F, Phaeochromocytoma--“the great mimic”: an unusual presentation, Emergency Medicine Journal, 24, 9, 672–3, September 2007, 17711956, 2464664, 10.1136/emj.2007.049569, It is estimated that approximately 0.1% of patients with hypertension have a pheochromocytoma, and it is often misdiagnosed as essential hypertension. As symptoms are often paroxysmal (episodic/sporadic), patients may not immediately seek treatment as the problem “disappears on its own.” Furthermore, when pictured in the ideal clinical scenario (an older woman in her mid-50s), the spontaneous attacks of flushing, sweating, and a racing heart may be mistaken for pre-menopausal related hot flashes. Unmanaged pheochromocytoma is dangerous and can lead to serious complications, including death.JOURNAL, Zuber SM, Kantorovich V, Pacak K, Hypertension in pheochromocytoma: characteristics and treatment, Endocrinology and Metabolism Clinics of North America, 40, 2, 295–311, vii, June 2011, 21565668, 3094542, 10.1016/j.ecl.2011.02.002, JOURNAL, Riester A, Weismann D, Quinkler M, Lichtenauer UD, Sommerey S, Halbritter R, Penning R, Spitzweg C, Schopohl J, Beuschlein F, Reincke M, 6, Life-threatening events in patients with pheochromocytoma, European Journal of Endocrinology, 173, 6, 757–64, December 2015, 26346138, 10.1530/EJE-15-0483, free, The cardiovascular system is the most commonly involved.JOURNAL, Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A, 23444609, Cardiovascular manifestations of phaeochromocytoma, Journal of Hypertension, 29, 11, 2049–60, November 2011, 21826022, 10.1097/HJH.0b013e32834a4ce9, JOURNAL, Young WF, 6009557, Adrenal causes of hypertension: pheochromocytoma and primary aldosteronism, Reviews in Endocrine & Metabolic Disorders, 8, 4, 309–20, December 2007, 17914676, 10.1007/s11154-007-9055-z, JOURNAL, Liao WB, Liu CF, Chiang CW, Kung CT, Lee CW, Cardiovascular manifestations of pheochromocytoma, The American Journal of Emergency Medicine, 18, 5, 622–5, September 2000, 10999582, 10.1053/ajem.2000.7341, In pregnancy, pheochromocytoma is associated with significant maternal and fetal mortality, mainly due to hypertensive crisis in the mother and intrauterine growth restriction in the fetus.JOURNAL, Lenders JW, Pheochromocytoma and pregnancy: a deceptive connection, European Journal of Endocrinology, 166, 2, 143–50, February 2012, 21890650, 10.1530/EJE-11-0528, free, JOURNAL, Kattah AG, Garovic VD, The management of hypertension in pregnancy, Advances in Chronic Kidney Disease, 20, 3, 229–39, May 2013, 23928387, 3925675, 10.1053/j.ackd.2013.01.014,

Cardiovascular system

1. Hypertensive crisis: Pheochromocytoma-related hypertensive emergencies are one of the most feared clinical manifestations. Attacks are random and may occur secondary to a trigger (see Signs and Symptoms above) or spontaneously after a catecholamine surge. The prevailing symptom is elevated systolic blood pressure (> 200 mmHg) that is unresponsive to traditional treatment regimens and threatens end-organ damage. Patients require immediate, life-saving treatment to prevent further damage to other organs and/or death.
2. Myocardial Ischemia/Infarction: A heart attack is often caused by a significant build-up of plaque (atherosclerosis) in the coronary vessels. Patients with pheochromocytoma present with myocardial infarctions despite an overall lack of plaque build-up, indicating a different mechanism for the myocardial infarction. Current research hypothesizes that the tumor secretes massive amounts of catecholamines, which directly interact with myocardial (heart) tissue and exert negative effects including oxygen deprivation, leading to accelerated scarring and cell death.
3. Toxic Myocarditis: Even in patients without myocardial damage, excessive catecholamines can result in abnormal ST changes on an ECG. Norepinephrine (a catecholamine) is hypothesized to result in damaged cardiac tissue by inhibiting coronary blood flow and depriving cells of oxygen, thus resulting in ischemic tissue. Fortunately, following tumor excision and the subsequent quelling of catecholamines, the damage has been proven reversible.
4. Cardiomyopathy: Pheochromocytomas have been implicated in various types of cardiomyopathy, including (myocarditis, see above), dilated cardiomyopathy, and stress-induced or Takotsubo cardiomyopathy.JOURNAL, Zhang R, Gupta D, Albert SG, Pheochromocytoma as a reversible cause of cardiomyopathy: Analysis and review of the literature, International Journal of Cardiology, 249, 319–323, December 2017, 29121733, 10.1016/j.ijcard.2017.07.014, As with the other cardiovascular-related complications, excess catecholamines are responsible for the increased myocardial burden and significant physiologic stress.JOURNAL, Agrawal S, Shirani J, Garg L, Singh A, Longo S, Longo A, Fegley M, Stone L, Razavi M, Radoianu N, Nanda S, 6, Pheochromocytoma and stress cardiomyopathy: Insight into pathogenesis, World Journal of Cardiology, 9, 3, 255–260, March 2017, 28400922, 5368675, 10.4330/wjc.v9.i3.255, free, {{psc|reason=Single retrospective study of 18 individuals, basically a case report|date=September 2020}} Current literature indicates that most of the catecholamine-induced damage is reversible, thereby strengthening the argument for early and accurate diagnosis in order to allow for cardiac remodeling and prevent further destruction.
5. Arrhythmias: Sinus tachycardia is the most common abnormal heart rhythm associated with a pheochromocytoma and is experienced by patients as the feeling of a “fluttering heart” or palpitations. Many other tachyarrhythmias (fast heart rate) have also been reported.

Nervous system

1. Cerebrovascular Accident (Stroke): Multiple reports have detailed transient ischemic attacks or strokes in patients with a pheochromocytoma.JOURNAL, Van YH, Wang HS, Lai CH, Lin JN, Lo FS, 37955071, Pheochromocytoma presenting as stroke in two Taiwanese children, Journal of Pediatric Endocrinology & Metabolism, 15, 9, 1563–7, November 2002, 12503867, 10.1515/jpem.2002.15.9.1563, {{psc|reason=Case report|date=September 2020}}JOURNAL, Abourazzak S, Atmani S, Arqam LE, Chaouki S, Labib S, Harrandou M, Tizniti S, Bouabdellah Y, Bouharrou A, Hida M, 6, Cerebral ischaemic stroke and bilateral pheochromocytoma, BMJ Case Reports, 2010, May 2010, bcr1220092535, 22736758, 3047554, 10.1136/bcr.12.2009.2535, JOURNAL, Dagartzikas MI, Sprague K, Carter G, Tobias JD, 44533238, Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma, Pediatric Emergency Care, 18, 1, 33–5, February 2002, 11862137, 10.1097/00006565-200202000-00011, free, JOURNAL, Cohen JK, Cisco RM, Scholten A, Mitmaker E, Duh QY, Pheochromocytoma crisis resulting in acute heart failure and cardioembolic stroke in a 37-year-old man, Surgery, 155, 4, 726–7, April 2014, 23305592, 10.1016/j.surg.2012.11.013, JOURNAL, Lin PC, Hsu JT, Chung CM, Chang ST, Pheochromocytoma Underlying Hypertension, Stroke, and Dilated Cardiomyopathy, Texas Heart Institute Journal, 2007, 34, 2, 244–6, 17622380, 1894695, 679006463, JOURNAL, Buchbinder NA, Yu R, Rosenbloom BE, Sherman CT, Silberman AW, Left ventricular thrombus and embolic stroke caused by a functional paraganglioma, Journal of Clinical Hypertension, 11, 12, 734–7, December 2009, 20021531, 10.1111/j.1751-7176.2009.00182.x, 8673247, 30275458, free, JOURNAL, Luiz HV, da Silva TN, Pereira BD, Santos JG, Gonçalves D, Manita I, Portugal J, 7618637, Malignant paraganglioma presenting with hemorrhagic stroke in a child, Pediatrics, 132, 6, e1709-14, December 2013, 24276837, 10.1542/peds.2013-0492, {{psc|reason=Multiple case reports are the only citations here.|date=September 2020}} In a study of 130 patients with pheochromocytoma, 7 patients were diagnosed with a transient ischemic attack (the neurologic deficit completely resolved) and 3 patients experienced a stroke with persistent symptoms.JOURNAL, Potapova G, Chazova I, Kuznetsov N, Sitina V, Popov E, Gavrilov I, Pheochromocytoma and Stroke, Journal of Hypertension, June 2011, 29, e505, 10.1097/00004872-201106001-01534,
2. Headache: Headaches are one of the core clinical manifestations of a pheochromocytoma and can result in debilitating pain. The majority of studied patients report their pain began and ended abruptly without warning and described the pain as a severe, bilateral throbbing (although the scale of severity was not published). While 71% of the studied patients reported headaches, just over 20% of the affected patients endorsed associated nausea, vomiting, photophobia, or phonophobia, which are typically associated with migraines.JOURNAL, Anderson NE, Chung K, Willoughby E, Croxson MS, 207005321, Neurological manifestations of phaeochromocytomas and secretory paragangliomas: a reappraisal, Journal of Neurology, Neurosurgery, and Psychiatry, 84, 4, 452–7, April 2013, 23204473, 10.1136/jnnp-2012-303028, {{psc|reason=Case report|date=September 2020}}

Urinary system

1. Acute Renal Failure: Several reports have detailed rhabdomyolysis (rapid skeletal muscle breakdown) leading to acute kidney injury and the need for transient dialysis in the undiagnosed pheochromocytoma patient as their primary presenting symptom.JOURNAL, Shemin D, Cohn PS, Zipin SB, Pheochromocytoma presenting as rhabdomyolysis and acute myoglobinuric renal failure, Archives of Internal Medicine, 150, 11, 2384–5, November 1990, 2241450, 10.1001/archinte.1990.00390220118024, JOURNAL, Hamada N, Akamatsu A, Joh T, A case of pheochromocytoma complicated with acute renal failure and cardiomyopathy, Japanese Circulation Journal, 57, 1, 84–90, January 1993, 8437346, 10.1253/jcj.57.84, free, JOURNAL, Celik H, Celik O, Guldiken S, Inal V, Puyan FO, Tugrul A, 2062065, Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report, Renal Failure, 36, 1, 104–7, February 2014, 24059440, 10.3109/0886022X.2013.832856, JOURNAL, Takabatake T, Kawabata M, Ohta H, Yamamoto Y, Ishida Y, Hara H, Hattori N, Acute renal failure and transient, massive proteinuria in a case of pheochromocytoma, Clinical Nephrology, 24, 1, 47–9, July 1985, 4017298, {{psc|reason=Multiple case reports cited as case reports, but a review would be better|date=September 2020}} Kidney failure is brought about by catecholamine-induced muscle injury. Norepinephrine causes vessels to narrow, thereby limiting blood flow and inducing ischemia.

Multiple organ dysfunction syndrome (MODS)JOURNAL, Lorz W, Cottier C, Imhof E, Gyr N, Multiple organ failure and coma as initial presentation of pheochromocytoma in a patient with multiple endocrine neoplasia (MEN) type II A, Intensive Care Medicine, 19, 4, 235–8, 1993, 8103532, 7095150, 10.1007/BF01694777, : Caused by an elevated inflammatory response, multiple organ dysfunction is a severe, life-threatening emergency with increasing mortality based on the number of systems involved.BOOK, Marshall JC,www.ncbi.nlm.nih.gov/books/NBK6868/, Holzheimer RG, Mannick JA, The multiple organ dysfunction syndrome, Surgical Treatment: Evidence-Based and Problem-Oriented, 2001, Munich, Zuckschwerdt, 978-3-88603-714-8, Pheochromocytoma-related MODS is associated with multiple organ failure, hyperthermia > 40 degrees Celsius, neurologic manifestations, and cardiovascular instability resulting in either hypo or hypertension.JOURNAL, Newell KA, Prinz RA, Pickleman J, Braithwaite S, Brooks M, Karson TH, Glisson S, Pheochromocytoma multisystem crisis. A surgical emergency, Archives of Surgery, 123, 8, 956–9, August 1988, 2899426, 10.1001/archsurg.1988.01400320042007, In contrast to a hypertensive crisis, pheochromocytoma-associated MODS may not respond to traditional alpha-receptor agents and may require emergent surgical excision if clinical stability is not achieved.Whitelaw BC, Prague JK, Mustafa OG, Schulte KM, Hopkins PA, Gilbert JA, McGregor AM, Aylwin SJ. Phaeochromocytoma [corrected] crisis. Clin Endocrinol (Oxf). 2014 Jan;80(1):13-22. doi: 10.1111/cen.12324. Epub 2013 Oct 17. Erratum in: Clin Endocrinol (Oxf). 2013 Mar;80(3):468. PMID: 24102156.

Genetics

Current estimates predict that upwards of 40% of all pheochromocytomas are related to an inherited germline susceptibility mutation.JOURNAL, Fishbein L, Pheochromocytoma and Paraganglioma: Genetics, Diagnosis, and Treatment, Hematology/Oncology Clinics of North America, 30, 1, 135–50, February 2016, 26614373, 10.1016/j.hoc.2015.09.006, Of the remaining 60% of tumors, more than 30% are associated with a somatic mutation.JOURNAL, Mercado-Asis LB, Wolf KI, Jochmanova I, Taïeb D, Pheochromocytoma: A Genetic and Diagnostic Update, Endocrine Practice, 24, 1, 78–90, January 2018, 29144820, 10.4158/EP-2017-0057, 45860930,hal.archives-ouvertes.fr/hal-01789514/file/Taieb%20Final%20Jun%2012%20submitted%20to%20Endocrine%20Practice.pdf, Given the high association with genetic inheritance, the United States Endocrine Society recommends that all patients diagnosed with a pheochromocytoma undergo an evaluation with a genetic counselor to consider genetic testing.JOURNAL, Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF, 6, Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline, The Journal of Clinical Endocrinology and Metabolism, 99, 6, 1915–42, June 2014, 24893135, 10.1210/jc.2014-1498, free, In the UK eligibility for NHS funded genetic testing is determined by criteria set by NHS England Genomics servicewww.england.nhs.uk/wp-content/uploads/2018/08/Rare-and-inherited-disease-eligibility-criteria-version-5.2.pdf The criteria in 2023 included all patients with paraganglioma and all patients with unilateral pheochromocytoma aged under 60www.england.nhs.uk/wp-content/uploads/2018/08/Rare-and-inherited-disease-eligibility-criteria-version-5.2.pdf The most recent data indicates that there are 25 pheochromocytoma susceptibility genes; however, just 12 are recognized as part of a well-known syndrome. Determining the genetic status of a pheochromocytoma patient is crucial – each gene is inherited in a different pattern, associated with specific disease characteristics, and may respond more favorably to certain treatment options. Furthermore, early identification can guide physicians on screening recommendations for first degree relatives of patients with pheochromocytoma.JOURNAL, Kavinga Gunawardane PT, Grossman A, The clinical genetics of phaeochromocytoma and paraganglioma, Archives of Endocrinology and Metabolism, 61, 5, 490–500, October 2017, 29166454, 10.1590/2359-3997000000299, free, 10522248, There is no current consensus for how and when asymptomatic carriers (individual who has a genetic variant associated with pheochromocytoma, but no current evidence of disease) should be evaluated. Conversations should occur at an individual level with the patient and their provider to develop a personalized screening plan that alternates between a biochemical (blood work) evaluation and whole-body imaging to monitor disease progression.JOURNAL, Jochmanova I, Wolf KI, King KS, Nambuba J, Wesley R, Martucci V, Raygada M, Adams KT, Prodanov T, Fojo AT, Lazurova I, Pacak K, 6, SDHB-related pheochromocytoma and paraganglioma penetrance and genotype–phenotype correlations, Journal of Cancer Research and Clinical Oncology, 143, 8, 1421–1435, August 2017, 28374168, 5505780, 10.1007/s00432-017-2397-3, {{psc|reason=This is a study - likely can replace this source/sentence with the treatment guidelines referenced above|date=September 2020}}

Pediatric considerations

Additional practices may help maintain the emotional and psychological well-being of the minor. Screening includes a multidisciplinary team (endocrinologist, oncologist, psychologist, geneticist, parent, and child) where the primary focus is supporting the child.{{primary source inline|date=August 2020}}JOURNAL, Lahlou-Laforêt K, Consoli SM, Jeunemaitre X, Gimenez-Roqueplo AP, Presymptomatic genetic testing in minors at risk of paraganglioma and pheochromocytoma: our experience of oncogenetic multidisciplinary consultation, Hormone and Metabolic Research, 44, 5, 354–8, May 2012, 22517555, 10.1055/s-0032-1311568, 28354220,

• A positive result from testing during family-observed days of celebration may mask the happiness associated with these events in the future.
• Testing one pediatric sibling at a time allows the family to narrow their focus when results are returned and support each sibling individually.
• A negative result may be upsetting to a child if their sibling was positive; an opportunity to ask questions and process results may be helpful.

Hereditary syndromes

The following table(s) detail the clinical characteristics of the well-known hereditary pheochromocytoma gene variantsJOURNAL, Neumann HP, Young WF, Krauss T, Bayley JP, Schiavi F, Opocher G, Boedeker CC, Tirosh A, Castinetti F, Ruf J, Beltsevich D, Walz M, Groeben HT, von Dobschuetz E, Gimm O, Wohllk N, Pfeifer M, Lourenço DM, Peczkowska M, Patocs A, Ngeow J, Makay Ö, Shah NS, Tischler A, Leijon H, Pennelli G, Villar Gómez de Las Heras K, Links TP, Bausch B, Eng C, 6, 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma, Endocrine-Related Cancer, 25, 8, T201–T219, August 2018, 29794110, 10.1530/ERC-18-0085, free, 11577/3302932, free, JOURNAL, Favier J, Amar L, Gimenez-Roqueplo AP, 26205361, Paraganglioma and phaeochromocytoma: from genetics to personalized medicine, Nature Reviews. Endocrinology, 11, 2, 101–11, February 2015, 25385035, 10.1038/nrendo.2014.188, JOURNAL, Dahia PL, 31457232, Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity, Nature Reviews. Cancer, 14, 2, 108–19, February 2014, 24442145, 10.1038/nrc3648, free, JOURNAL, Jochmanova I, Pacak K, Genomic Landscape of Pheochromocytoma and Paraganglioma, Trends in Cancer, 4, 1, 6–9, January 2018, 29413423, 5819363, 10.1016/j.trecan.2017.11.001, {| class=“wikitable“|+Classic Pheochromocytoma Tumor Syndromes!!Gene!Inheritance!Penetrance!Metastatic Potential!1o Disease Characteristics!MEN2|RETAutosomal Dominant|40–50%|

• Hypoxia-inducible factor 2 alpha (HIF2A)
• Polycythemia
• Duodenal somatostatinoma
• Retinal and choroidal vascular changes
• Paraganglioma/Pheochromocytoma
1. Pheochromocytoma and Giant Cell Tumor of Bone