Evolving Clinical Presentation and Assessment of Pheochromocytoma: A Review

Leilani B. Mercado-Asis, Ria Mari S. Siao, Neil Francis A. Amba

Sep 2017 DOI 10.35460/2546-1621.2017-0050     Access   

Abstract

Pheochromocytoma (PHEO) is a neuroendocrine lesion in the adrenal medulla composed of chromaffin cells producing excess amount of catecholamines. These tumoral cells have the property to synthesize, metabolize, store, and secrete catecholamines and their metabolites. The clinical symptomatology is derived from the peripheral tissue effect of norepinephrine, epinephrine, and their by-products. Morbidity and mortality is increased due to the delay in the diagnosis and treatment. A high index of suspicion leads to testing for PHEO through biochemical, imaging, and genetic studies. Dilemma in its assessment comes about when the clinical picture is beset by too much catecholamine secretory periodicity, too little catecholamine secretion, in lesions less than 1 cm, in exclusively dopamine-secreting tumors, and in the unavailability of biochemical tests and imaging.

The aim of this review is to focus on the progress in the approach of early diagnosis of pheochromocytoma through improved clinical, biochemical, and imaging modalities. Emphasis is made on the early recognition of evolving clinical presentations, with the introduction of cardiovascular imaging, 2D echocardiogram, and cardiac MRI in the early diagnosis of patients with no risk factors and with equivocal biochemical and imaging results yet present with cardiovascular events. From the data reviewed and presented, several algorithms are proposed by the authors as an easy guide for clinicians in the diagnostic approach of pheochromocytoma.

  1. Sutton MG, Sheps SG & Lie Ll. Prevalence of clinically unsuspected pheochromocytoma. Mayo Clinic Proceedings. 1981; 56 354-60.
  2. Sinclair AM, Isles CG, Brown I, Cameron H, Murray GD, & Robertson JW. Secondary hypertension in a blood pressure clinic. Archives of Internal Medicine. 1987; 147 1289-1293.
  3. Anderson GH, Jr., Blakeman N, Streeten DH. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. Journal of Hypertension. 1994; 12 609-615.
  4. Eisenhofer G, JW Lenders, WM Linehan, MW Walther, DS Goldstein, & HR Keiser. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von hippel-lindau disease and multiple endocrine neoplasia type 2. New England Journal of Medicine. 1999; 340 1872-1879.
  5. Dluhy RG. Pheochromocytoma — death of an axiom. New England Journal of Medicine. 2002; 346 1486 -1488. doi: 10.1056/NEJM200205093461911.
  6. Eisenhofer G & Peitzsch M. Laboratory evaluation of pheochromocytoma and paraganglioma. Clinical Chemistry. 2014; 60 1486-1499; DOI: 10.1373/clinchem.2014.224832.
  7. Lance JW & Hinterberger H. The headached of pheochromocytoma. Proceedings of the Australian Association of Neurologists. 1975; 12 49-53.
  8. Manger WM & Gifford RW Clinical and experimental Pheochromocytoma. Second Edition.Blackwell Science; Cambridge1996.
  9. Young WF Jr & Maddox DE Spells:in search of cause. Mayo Clinic Proceedings 199570 757-765.
  10. Lenders JWM, Eisenhofer G, Mannelli M, & Pacak K. Phaeochromocytoma. Lancet .2005; 366 665–675.
  11. Lenders JWM & Eisenhofer G. Pathophysiology and diagnosis of disorders of the adrenal medulla: focus on pheochromocytoma. Comprehensive Physiology. 2014; 4 691-713. (10.1002/cphy.c130034).
  12. Gimenez-Roqueplo AP, Dahia PL & Robledo M. An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes. Hormone and Metabolic Research. 2012; 44 328-333.
  13. Zuber S, Kantorovich V, Pacak K. Hypertension in Pheochromocytoma: Characteristics and Treatment. Endocrinology Metabolism Clinics of North America. 2011; 40 295–311. (doi:10.1016/j.ecl.2011.02.002).
  14. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, Ploos van Amstel HK, Lips CJM, Nishisho I, Takai SI et al. The Relationship Between Specific RET Proto-oncogene Mutations and Disease Phenotype in Multiple Endocrine Neoplasia Type 2International RET Mutation Consortium Analysis. Journal of American Medical Association. 1996; 276 1575-1579. doi:10.1001/jama.1996.03540190047028.
  15. Hernandez FC, Sanchez M, Alvarez A, Diaz J, Pascual R, Perez M, Tovar I & Martinez P. A five-year report on experience in the detection of pheochromocytoma. Clinical Biochemistry. 2000; 33 649–55.
  16. Eisenhofer G, Ehrhart-Bornstein M & Bornstein S. The adrenal medulla. physiology and pathophysiology. In: Bolis CL LJ, Govoni S, editor. Handbook of the Autonomic Nervous System in Health and Disease. 2003; pp. 185-224. New York, Basel: Marcel Dekker Inc.
  17. Eisenhofer G, Lenders JW, Timmers HJLM, Mannelli M, Grebe SK, Hofbauer LC, Bornstein SR, Tiebel O, Adams K, Bratslavsky G. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clinical Chemistry. 2011; 57 411-420.
  18. Kudva YC, Sawka AM & Young WF Jr. The Laboratory Diagnosis of Adrenal Pheochromocytoma: The Mayo Clinic. Journal of Clinical Endocrinology & Metabolism. 2003; 88.
  19. Boyle JG, Davidson DF, Perry CG & Connell JM. Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. Journal of Clinical Endocrinology & Metabolism. 2007; 92 4602–4608.
  20. Erlic Z, Rybicki L, Peczkowska M, Golcher H, Kann PH, Brauckhoff M, Mussig K, Muresan M, Schaffler A, Reisch N et al. European-American Pheochromocytoma Study G. Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients. Clinical Cancer Research. 2009; 15 6378-6385.
  21. Zhuang Z, Yang C, Lorenzo F, Merino M, Fojo T, Kebebew E, PopovicV, Stratakis CA, Prchal JT & Pacak K. Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia. New England Journal of Medicine. 2012; 367 922-930.
  22. Dahia PLM. The genetic landscape of pheochromocytomas and paraganglioms: somatic mutations take center stage. Journal of Endocrinology & Metabolism. 2013; 98 2679-2681.
  23. Lorenzo FR, Yang C, Ng Tang Fui M, Vankayalapati H, Zhuang Z, Huynh T, Grossmann M, Pacak K & Prchal JT. A novel EPAS1/HIF2A germline mutation in a congenital polycythemia with paraganglioma. Journal of Molecular Medicine (Berl). 2013;91 507-512.
  24. Pacak K, Linehan WM, Eisenhofer G, Walther MW & Goldstein DS. Recent advances in genetics, diagnosis, localization and treatment of pheochromocytoma. Annals of Internal Medicine. 2001; 134 315-329.
  25. Timmers HJLM, Pacak K, Huynh TT, Abu-Asab M, Tsokos M, Merino MJ, Baysal BE, Adams KT & Eisenhofer G. Biochemically silent abdominal paragangliomas in patients with mutations in the succinate dehydrogenase subunit B gene. Journal of Clinical Endocrinology & Metabolism. 2008; 93 4826-4832.
  26. Eisenhofer G, Lenders JW, Timmers HJLM, Mannelli M, Grebe SK, Hofbauer LC, Bornstein SR, Tiebel O, Adams K, Bratslavsky G. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clinical Chemistry. 2011; 57 411-420.
  27. Eisenhofer G, Lenders JW, Siegert G, Bornstein SR, Friberg P, Milosevic D, Mannelli M, Linehan WM, Adams K, Timmers HJLM et al. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. European Journal of Cancer. 2012; 48 1739-1749. (doi:10.016/j.ejca .2011.07.016).
  28. Eisenhofer G Pathophysiology and diagnosis of disorders of the adrenal medulla: focus on pheochromocytoma. Comprehensive Physiology. 2014; 4 691-713. (10.1002/cphy.c130034)
  29. Eisenhofer G & Peitzsch M. Laboratory evaluation of pheochromocytoma and paraganglioma. Clinical Chemistry. 2014; 60 1486-1499; DOI: 10.1373/clinchem.2014.224832.
  30. Richter S, Peitzsch M, Rapizzi E, Lenders JW, Qin N, de Cubas AA, Schiavi F, Rao JU, Beuschlein F, Quinkler M et al. Krebs cycle metabolite profiling for identification nd stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency. Journal of Endocrinology & Metabolism. 2014; 99 3903-3911.
  31. Janssen I, Blanchet EM, Adams K, Chen CC, Millo CM, Herscovitch P, Taieb D, Kebebew E, Lehnert H, Fojo AT et al Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clinical Cancer Research. 2015; 21 3888-3895.
  32. Yang C, Zhuang Z, Fliedner SMJ, Shankavaram U, Sun MG, Bullova P, Zhu R, Elkahloun AG, Kourlas PJ, Merino M et al. Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia. Journal of Molecular Medicine. 2015; 93 93-104.
  33. Toledo RA, Qin Y, Cheng Z, Gao Q, Iwata S, Silva GM, Prasad M, Ocal T, Rao S, Aronin N et al Recurrent mutations of chromatin-remodeling genes and kinase receptors in pheochromocytoma and paragangliomas. Clinical Cancer Research. 2016; OF1 – OF11.
  34. Rowbotham DA, Enfield KSS, Martinez VD, Thu KL, Vucic EA, Stewart GL, Bennewith KL & Lam WL . Multiple components of the VHL tumor suppressor complex are frequently affected by DNA copy number loss in pheochromocytoma. International Journal of Endocrinology .2014; 1-9.
  35. Gupta P, Khurana ML, Khadgaawat R, Kumar G & Tandon. Plasma metanephrine, normetanephrine, and 3-methoxytyramine for the diagnosis of pheochromocytoma. Indian Journal of Endocrinology and Metabolism. 2015; 19 663-638.
  36. LeDouarin & Kalcheim 2nd ed The Neural Crest Cambridge University Press, Cambridge1999.
  37. Shtukmaster S, Schier MC, Huber K, Krispin S, Kalchiem C & Unsicker Klaus Sympathetic neurons and chromaffin cells share a common progenitor in the neural crest in vivo. Neural Development .2003; 8 12.
  38. Huber K, Kalcheim C & Unsicker K. The development of the chromaffin cell lineage from the neural crest. Autonomic Neuroscience. 2009; 151 10-16.
  39. Rohrer H . Transcriptional control of differentiation and neurogenesis in autonomic ganglia. European Journal of Neuroscience. 2011; 34 1563-1573.
  40. Unsicker K, Huber K, Schober A & Kalcheim C. Resolved and open issues in chomaffin cell development. Mechanism of Development. 2013; 130 324-329.
  41. Konno H, Handa T & Alonzo D, Taylor. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. European Journal of Pharmaceutics and Biopharmaceutics. 2008;70 493-499.
  42. Unsicker K, Krisch B, Otten U & Thoenen H. Nerve growth factor-induced fiber outgrowth from isolated rat adrenal medullary cells: impairment by glucocorticoids. Proceedings of the National Academy of Sciences of the United States of America. 1978; 74 3498-3504.
  43. Anderson DJ. Molecular control of cell fate in the sympathoadrenal cell lineage. Annual Review of Neurology Science. 1993; 16 129-158.
  44. Michelson AM & Anderson DM. Changes in competence determine the timing of the two sequential glucocorticoid effects on sympathoadrenal progenitors. Neuron. 1993; 8 589-604.
  45. Unsicker K. The chromaffin cell: paradigm in cell, developmental and growth factor biology. Journal of Anatomy. 1993; 183 207-221.
  46. Unsicker K, Stahnke G, & Muller TH. Survival,morphology,and cathecolamine storage of chromaffin cells serum-free culture: evidence for a survival and differentiation promoting activity in medium conditioned by purified chromaffin cells. Neurochemistry Residence .1987; 12 995-1003.
  47. Finotto S, Krieglstein K, Schober A, Deimling F, Lindner K, Bruhl B, Beier K, Metz J, Garcia-Arraras JE, Roig-Lopez J et al. Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells. Development. 1999; 126: 2935-2944.
  48. Nagatsu T, Levitt M & Udenfriend S. Tyrosine hydroxylase: The Initial step in norepinephrine biosynthesis. Journal of Biological Chemistry. 1964; 239:2910-2917.
  49. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR & Pacak K. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. Journal of Clinical Endocrinology & Metabolism. 2003b; 88 2656–2666. (doi:10.1210/ jc.2002-030005).
  50. Livett BG. Adrenal medullary chromaffin cells in vitro. Physiological Reviews. 1984; 64 1103-1161.
  51. Eisenhofer G, Rundquist B, Aneman A, Friberg P, Dakak N, Kopin IJ, Jacobs MC, & Lenders JW Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines. Journal of Clinical Endocrinology & Metabolism. 1995b; 80: 3009-3017.
  52. Eisenhofer G, Friberg P, Pacak K, Goldstein DS, Murphy DL, Tsigos C, Quyyumi AA, Brunner HG & Lenders JW. Plasma metadrenalines: Do they provide useful information about sympatho-adrenal function and catecholamine metabolism? Clinical Science (Lond). 1995a; 88: 533-542.
  53. Eisenhofer G, Pecorella W, Pacak K, Hooper D, Kopin I & Goldstein D. The neuronal and extraneuronal origins of plasma 3-methoxy-4-hydroxyphenylgycol in rats. The Journal of Auto-Nomic Nervous System. 1994; 50 93-107.
  54. Eisenhofer G, Huynh TT, Hiroi M & Pacak K. Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma. Reviews in Endocrine and Metabolic Disorders. 2001a; 2: 297-311.
  55. Sjoerdsma A, King WM, Leeper L & Udenfriend S. Demonstration ofthe 3-methoxy analog of norepinephrine in man. Science. 1957;127 876.
  56. Sjoerdsma A. Catecholamine metabolism in patients with pheochromocytoma. Pharmacological Reviews. 1959;11 :374-378.
  57. Crout JR & Sjoerdsma A. Turnover and metabolism of catecholamines in patients with pheochromocytoma. Journal of Clinical Investigation. 1964; 43: 94-102.
  58. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW. Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. Journal of Clinical Endocrinology & Metabolism. 1998; 83: 2175-2185.
  59. Eisenhofer G, Goldstein DS, Sullivan P, Csako G, Brouwers FM, Lai EW, Adams KT & Pacak K . Biochemical and clinical manifestations of dopamine-producing paragangliomas: utility of plasma methoxytyramine. Journal of Clinical Endocrinology & Metabolism. 2005; 90 2068-2075.
  60. Goldstein DS, Swoboda KJ, Miles JM, Coppack SW, Aneman A, Holmes C, Lamensdorf I & Eisenhofer G. Sources and physiological significance of plasma dopamine sulfate. Journal of Clinical Endocrinology & Metabolism. 1999; 87: 2523-2531.
  61. Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC, et al. Plasma metanephrines in the diagnosis of pheochromocytoma. Annals of Internal Medicine. 1995;123:101-109.
  62. Pamporaki C, Darr R, Bursztyn M, Glockner S, Bornstein SR, Lenders JWM, et al. Plasma-free vs deconjugated metanephrines for diagnosis of phaeochromocytoma. Clinical Endocrinology (Oxford). 2013;79:476-483.
  63. Khorram-Manesh A, Ahlman H, Nilsson O, Odén A & Jansson S. Mortality associated with pheochromocytoma in a large Swedish cohort. European Journal of Surgical Oncology. 2004; 30: 556-559.
  64. Pacak K. Pheochromocytoma: a catecholamine and oxidative stress disorder. Endocrine Regulations. 2011; 45: 65–90.
  65. Stolk RF, Bakx C, Mulder J, Timmers HJLM & Lenders JWM. Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines? Journal of Clinical Endocrinology & Metabolism. 2013; 98 1100-6 doi: 10.1210/jc.2012-3669.
  66. Pourian M, Mostafazadeh DB & Soltani A. Does ths patient have pheochromocytoma? A systematic review of clinical signs and symptoms. Journal of Diabetes & Metabolic Disorders .2016; 15:1-12.
  67. Maurice JB, Troke R, Win Z, Ramachandran R, Al-Nahhas A, Naji M, et al. A comparison of the performance of 68Ga-DOTATATE PET/CT and 123I-MIBG SPECT in the diagnosis and follow-up of phaeochromocytoma and paraganglioma. European Journal Nuclear Medicine and Molecular Imaging. 2012; 39:1266-1270.
  68. Taieb D, Neumann HP, Rubello D, Al-Nahhas A, Guillet B & Hindie E. Modern nuclear imaging for paragangliomas: Beyond SPECT. Journal of Nuclear Medicine. 2012; 53:264-274.
  69. Lenders JWM, Willemsen JJ, Eisenhofer G, Ross HA, Pacak K, Timmers HJLM & Sweep CG. Is supine rest necessary before blood sampling for plasma metanephrines? Clinical Chemistry.2007; 53: 352-354.
  70. Tulen JH, Boomsma F & Man In’t Veld AJ. Cardiovascular control and plasma catecholamines during rest and mental stress: effects of posture. Clinical Science (London).1999; 96: 567-576.
  71. de Jong W, Eisenhofer G, Post W, Muskiet F, de Vries E, & Kema I. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. Journal of Clinical Endocrinology & Metabolism. 2009; 94: 2841–2849.
  72. van Berkel A, Lenders J & Timmers HJLM. Biochemical diagnosis of phaeochromocytoma and paraganglioma. European Journal of Endocrinology. 2014; 170: R109–R119.
  73. Eisenhofer G, Peitzsch M & McWhinney B. Impact of LC-MS/MS on the laboratory diagnosis of catecholamine producing tumors. Trends in Analytical Chemistry. 2016; 1-11 (doi: 10.1016/j.trac.2016.01.027)
  74. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W & Lambert G. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988; 11: 3-20.
  75. Dobri G, Bravo E & Hamrahian A. Pheochromocytoma: pitfalls in the biochemical evaluation. Expert Review of Endocrinology &. Metabolism. 2014; 9:123–135.
  76. Sawka AM, Jaeschke R, Singh RJ & Young WF Jr. A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. Journal of Clinical Endocrinology & Metabolism. 2003; 88: 553-558.
  77. Eisenhofer G, Lenders JW, Siegert G, Bornstein SR, Friberg P, Milosevic D, et al. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. European Journal of Cancer. 2012; 48: 1739-1749. (doi:10.016/j.ejca .2011.07.016).
  78. Unger N, Pitt C, Schmidt IL, Walz MK, Schmid KW, Philipp T, Philipp T, et al. Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. European Journal of Endocrinology. 2006; 154: 409–17.
  79. Pussard E, Chaouch A, Said T. Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine-producing tumors. Clinical Chemistry and Laboratory Medicine. 2014; 52: 437–44.
  80. Pillai D, & Callen S. Pilot quality assurance programme for plasma metanephrines. Annals of Clinical Biochemistry. 2010; 47:137–42.
  81. Whiting MJ. Simultaneous measurement of urinary metanephrines and catecholamines by liquid chromatography with tandem mass spectrometric detection. Annals of Clinical Biochemistry. 2009; 46: 129–36.
  82. Peitzsch M, Pelzel D, Glockner S, Prejbisz A, Fassnacht M, Beuschlein F, et al. Simultaneous liquid chromatography tandem mass spectrometric determination of urinary free metanephrines and catecholamines, with comparisons of free and deconjugated metabolites. Clinica Chimica Acta. 2013 ; 418: 50–8a.
  83. Peitzsch M, Prejbisz A, Kroiss M, Beuschlein F, Arlt W, Januszewicz A, et al. Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma. Annals of Clinical Biochemistry. 2013; 50: 147–55b.
  84. Lagerstedt SA, O’Kane DJ & Singh RJ. Measurement of plasma free metanephrine and normetanephrine by liquid chromatography-tandem mass spectrometry for diagnosis of pheochromocytoma. Clinical Chemistry.2004; 50: 603–11.
  85. Lendvai N, Pawlosky R, Bullova P, et al. Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: initial experimental and ex vivo findings. Endocrinology. 2014;155:27-32.
  86. Rao JU, Engelke UF, Sweep FC, et al. Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics. J Clin Endocrinol Metab. 2015;100:E214-222.
  87. Imperiale A, Moussallieh FM, Roche P, et al. Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications. Neoplasia. 2015;17:55-65.
  88. Guimarães S & Moura D. Vascular adrenoceptors: an update. Pharmacological Reviews. 2001; 53 :319-356.
  89. Ruffolo RR, Jr. and Hieble JP. Adrenoceptor pharmacology: Urogenital applications. European Urology . 1999 ;36: 17-22.
  90. Zhong H & Minneman K. α1-Adrenoceptor subtypes. European Journal of Pharmacology . 1999; 37: 5261-276.
  91. Agryle SA& McGrath JC . An α1A/α1L-Adrenoceptor Mediates Contraction of Canine Subcutaneous Resistance Arteries. Journal of Pharmacology And Experimental Therapeutics . 2000 ; 295: 627-633.
  92. Guimaraes S, Brandao F, & Paiva MQ. A study of the adrenoceptor-mediated feedback mechanisms by using adrenaline as a false transmitter. Naunyn-Schmiedeberg's Archives of Pharmacology. 1978; 305: 185-188.
  93. Begonha R, Moura D & Gemaraes S. Vascular β-Adrenoceptor-mediated Relaxation and the Tone of the Tissue in Canine Arteries. Journal of Pharmacy and Pharmacology. 1995; 510-513. (doi: 10.1111/j.2042-7158.1995tb05840).
  94. Gardner D & Shoback D. Pheochromocytoma and paraganglioma. Basic Clinical Endocrinology edn 9. Greenspans. Lange 2011.
  95. de Miguel Vl, Arias A, Paissan A,Pérez de Arenaza D, Pietrani M, Jurado A, Jaén A & Fainstein Day P. Catecholamine-Induced Myocarditis in Pheochromocytoma. Circulation. 2014; 129: 1348-1349. (doi: 10.1161/CIRCULATIONAHA.113.002762).
  96. Sanchez-Recalde A, Costero O, Oliver JM, Iborra C, Ruiz E & Sobrino JA. Pheochromocytoma-related cardiomyopathy inverted Takotsubo contractile pattern. Circulation. 2006; 113 e738-e739.doi 10.1161/CIRCULATIONAHA.105.581108.
  97. Mercado-Asis LB, Tingcungco AG, Bolong DT, Lopez RA, Caguioa EV, Yamamoto ME, et al. Diagnosis of small adrenal pheochromocytoma by adrenal venous sampling with glucagon stimulation test. International Journal of Endocrinology and Metabolism. 2011; 9 :323-329.
  98. Malong CHP, Tanchee-Ngo MJ, Torres-Salvador P, Pacak K & Mercado-Asis LB. Removal of dominant adrenal lateralized by glucagon-stimulated adrenal venous sampling alleviates hypertension in bilateral pheochromocytoma. Journal of Life Sciences. 2013; 7: 586-591.
  99. Zhou G, et al. Diagnosis and surgical treatment of multiple endocrine neoplasia. Chinese Medical Journal.2009;122(13):1495-1500.
  100. Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad SJ et al. Cardiovascular magnetic resonance in myocarditis: a JACC white paper. Journal of the American College of Cardiology 2009.53: 1475-1487.
  101. Dubois LA & Gray DK Dopamine-secreting pheochromocytomas: in search of a syndrome. World Journal of Surgery. 2005;29: 909-913.
  102. Amar L, Peyrard S, Rossignol P, Zinzindohoue F, Gimenez-Roqueplo AP, et al. Changes in urinary total metanephrine excretion in recurrent and malignant pheochromocytomas and secreting paragangliomas. Annals of the New York Academy of Sciences. 2006; 1073: 383-391. (doi:10.1196/annals.1353.042).
  103. Feldman JM. Phenylethanolamine-N-methyltransferase activity determines the epinephrine concentration of pheochromocytomas. Research Communications in Chemical Pathology and Pharmacology Journal. 1981 ; 34: 389–398.
  104. Yasunari K, Kohno M, Yoshikawa J. A dopamine-secreting pheochromocytoma. American Journal of Medicine. 1999; 106: 599-600.
  105. Schlumberger M, Gicquel C, Lumbroso J, Tenenbaum F, Comoy E, Bosq J, et al. Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. Journal of Endocrinogical Investigation 2002; 15: 631-642.
  106. Timmers HJ, Kozupa A, Eisenhofer G, et al. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. Journal of Clinical Endocrinology & Metabolism. 2007; 92: 779-786.
  107. Kimura N, Miura Y, Nagatsu I & Nagura H. Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma. Virchows Arch. A Pathology Anatomy and Histopathology. 1992; 421: 25–32.
  108. Turkova H, Prodanov T, Maly M, Martucci V, Adams K, Widimsky J Jr, et al. Characteristic and outcomes of metastatic SDHB and sporadic pheochromocytoma/paraganglioma: A National Institutes of Health study. Endocrine Practice. 2016; 22: 302-312.
  109. Palmar I, Vircburger M, Manojlovic D, Radevic B, Andjelkovic Z, Buric B, et al. [The von Hippel-Lindau syndrome with pheochromocytoma]. Srpski Arhiv Celokupno Lekarstvo . 2002 ; 2: 43-46.
  110. Figueroa SC, Khan U, Kurukulasuriya LR, Gardner D & Sowers JR. Surgical cure of hypertension in a patient with MEN 2A syndrome and mixed dopamine, metanephrine pheochromocytoma. Journal of Clinical Hypertension (Greenwich) 2010 ; 12: 439- 443.
  111. Dubey RK, Verma N & Pandey CK. Anaesthetic management of a dopamine-secreting phaeochromocytoma in multiple endocrine neoplasia 2B syndrome. Indian Journal of Anaesthesia. 2014; 58: 217-219.
  112. Teasdale S, & Reda E. Neurofibromatosis-related phaeochromocytoma: two cases with large tumours and elevated plasma methoxytyramine. Endocrinology Diabetes & Metabolism Case Reports .2015; 150-159.
  113. Ilias I, Sahdev A, Reznek RH, Grossman AB & Pacak K. The optimal imaging of adrenal tumours: a comparison of different methods. Endocrine- Related Cancer. 2007;14: 587-599. (doi: 10.1677/ERC-07-0045).
  114. Jalil ND, Pattou FN, Combemale F, Chapuis Y, Henry JF, Peix JL & Proye CA. Effectiveness and limits of preoperative imaging studies for the localisation of pheochromocytomas and paragangliomas: A review of 282 cases. French Association of Surgery (AFC), and The French Association of Endocrine Surgeons (AFCE). European Journal of Surgery.1998; 164: 23-28.
  115. Sahdev A, Sohaib A, Monson JP, Grossma AB, Chew SL, & Reznek RH. CT and MR imaging of unusual locations of extra-adrenal paragangliomas (pheochromocytomas). European Radiology.2005;15: 85-92.
  116. Leung K, Stamm M, Raja A & Low G. Pheochromocytoma: the range of appearances on ultrasound, CT, MRI, and functional imaging. AJR American Journal of Roentgenology . 2013; 200: 370–378. (doi: 10.2214/AJR.12.9126).
  117. Cistaro A, Niccoli Asabella A, Coppolino P, Quartuccio N, Altini C, Cucinotta M, et al. Diagnostic and prognostic value of ¹8F-FDG PET/CT in comparison with morphological imaging in primary adrenal gland malignancies - a multicenter experience. Hellenic Journal of Nuclear Medicine. 2015; 18: 97-102.
  118. Fiebrich HB, Brouwers AH, Kerstens MN, Pijl ME, Kema IP, de Jong JR, et al. 6-F-18Fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to conventional imaging with ¹²³I-metaiodobenzylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess. Journal of Clinical Endocrinology & Metabolism. 2009; 94: 922-30. doi: 10.1210/jc.2009-1054. Epub 2009 Jul 21.
  119. Timmers HJLM, Chen CC, Carrasquillo JA, Whatley M, Ling A, Eisenhofer G, et al. Staging and functional characterization of pheochromocytoma and paraganglioma by ¹8F-fluorodeoxyglucose (¹8F-FDG) positron emission tomography. Journal of National Cancer Institute . 2012 ;104: 700-8. (doi: 10.1093/jnci/djs188). Epub 2012 Apr 18.
  120. Timmers HJLM, TaiebD & Pacak K. Current and future anatomical and functional imaging approaches to pheochromocytoma and paraganglioma. Hormone and Metabolic Research. 2012 ; 44: 367-372.
  121. King KS, Prodanov T, Kantorovich V, Fojo T, Hewitt JK, Zacharin M, et al. Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: Significant link to SDHB mutations. Journal of Clinical Oncology. 2011; 29: 4137-4142.
  122. Martucci VL, Pacak K. Pheochromocytoma and paraganglioma: diagnosis, genetics, management, and treatment. Current Problems in Cancer. 2014; 38: 7-41. doi: 10.1016/j.currproblcancer.2014.01.001.
  123. Furuta N, Kiyota H, Yoshigoe F, Hasegawa N, & Ohishi Y. Diagnosis of pheochromocytoma using ¹²³I-compared with ¹³¹I-metaiodobenzylguanidine scintigraphy. International Journal of Urology . 1999 ; 6:119–124.
  124. Chen CC & Carrasquillo JA . Molecular imaging of adrenal neoplasms. Journal of Surgical Oncology. 2012; 106: 532–542.
  125. Derlin T, Busch JD, Wisotzki C, Schoennagel BP, Bannas P, Papp L, & Habermann CR. Intraindividual comparison of ¹²³I-mIBG SPECT/MRI,¹²³I-mIBG SPECT/CT, and MRI for the detection of adrenal pheochromocytoma in patients with elevated urine or plasma catecholamines. Clinical Nuclear Medicine 2013 ; 38: e1–6.
  126. Fonte J, Robles J, Chen C, Reynolds J, Whatley M, Ling A, Mercado-Asis LB, et al. False-negative ¹²³I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease. Endocrine-Related Cancer. 2012; 13: 83-93.
  127. Hartung-Knemeyer V, Rosenbaum-Krumme S, Buchbender C, Pöppel T, Brandau W, Jentzen W, et al. Malignant pheochromocytoma imaging with 124IMBG PET/MR. Journal of Clinical Endocrinology & Metabolism . 2012; 97: 3833-4. (doi: 10.1210/jc.2012-1958. Epub 2012 Sep 7).
  128. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma. Thyroid . 2010; 20:527-33. doi: 10.1089/thy.2009.0342.
  129. Zelinka T, Timmers HJLM, Kozupall A, Chen CC, Carrasquillo JA, Reynolds JC, et al. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocrine-Related Cancer. 2008; 15:311-323.
  130. Timmers HJLM, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, et al. Comparison of 18F-fluoro-L-DOPA, 18Ffluoro-deoxyglucose, and 18F-fluorodopamine PET and ¹²³I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. Journal of Clinical Endocrinology & Metabolism. 2009 ;94: 4757– 4767.
  131. Timmers HJLM, Eisenhofer G, Carrasquillo JA, Chen CC, Whatley M, Ling A, et al. Use of 18F]-fluorodopamine positronemission tomography (PET) as first-line investigation for the diagnosis and localization of nonmetastatic and metastatic phaeochromocytoma (PHEO). Clinical Endocrinology (Oxford). 2009; 71: 11–17.
  132. Peitzsch M, Prejbisz A, Kroiss M, Beuschlein F, Arlt W, Januszewicz A, et al. Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma. Annals of Clinical Biochemistry .2013 ;50 :147–55b.
  133. Gimenez-Roqueplo AP, Caumont-Prim A, Houzard C, Hignette C, Hernigou A, Halimi P, et al. Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: A multicenter prospective study from the PGL.EVA Investigators. Journal of Clinical Endocrinology & Metabolism. 2013 ; 98: E162-173.
  134. Eisenhofer G, Lattke P, Herberg M, Siegert G, Qin N, Da¨rr R, et al. Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma. Ann Clin Biochem. 2013; 50: 62–69.

Articles related to the one you are viewing

There are currently no results to show, please try again later

CC BY: Open Access Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/