The Protean Manifestations of Pheochromocytoma

Abstract

The treacherous and deceptive nature of pheochromocytoma makes it crucial to detect and treat it promptly; otherwise it will almost certainly be fatal from cardiovascular complications or metastases. Hypertension occurring in patients with pheochromocytomas is sustained in about 50% and paroxysmal in the remainder; however, many patients remain normotensive. Hypertension attacks may be precipitated by physical activity, postural changes, anxiety, certain foods or wine, some drugs, operative procedures, etc. Cardinal manifestations are paroxysmal hypertension, headache, palpitations ± tachycardia, inappropriate sweating; anxiety, tremulousness, pallor (rarely flushing), chest and abdominal pains; nausea and vomiting often occur. Hypercatecholaminemia manifestations are more common and pronounced when paroxysmal hypertension occurs, but persons with familial pheochromocytoma may be asymptomatic. Protean manifestations of pheochromocytoma may simulate many conditions, some of which may have elevated plasma and urine catecholamines and their metabolites. Baro-reflex failure, postural tachycardia syndrome, sleep apnea, carcinoid, renal failure, and pseudopheochromocytoma may be diagnostic challenges. The history, physical examination, biochemical testing (after eliminating interfering drugs, when possible) for plasma and urinary metanephrines can usually establish or exclude presence of pheochromocytomas. Occasionally a clonidine suppression test is needed to differentiate neurogenic from pheochromocytic hypertension. Manifestations suggesting hypercatecholaminemia without hypertension are highly atypical of pheochromocytoma. Pheochromocytoma may present as panic attacks, pre-eclampsia, cardiomyopathy, infection with fever and leucocytosis, diabetes, migraine, shock, Cushing's syndrome, multiple organ failure with lactic acidosis, neurological manifestations, transitory electrocardiogram abnormalities, constipation, intestinal obstruction, visual impairment, convulsions, etc. The key to diagnosis is always to think of pheochromocytoma in the differential diagnosis of hypertension.

Key words

adrenal tumor - catecholamines - multiple endocrine neoplasia type 2 - pheochromocytoma - hypertension - medullary thyroid carcinoma

References

• 1 Manger WM, Gifford  Jr  RW. Clinical and Experimental Pheochromocytoma. Cambridge, MA: Blackwell Science 1996
• 2 Bausch B, Boedeker CC, Berlis A, Brink I, Cybulla M, Walz MK, Januszewicz A, Letizia C, Opocher G, Eng C, Neumann HP. Genetic and clinical inverstigation of pheochromocytoma: a 22-year experience, from Freiburg, Germany to international effort.  Ann NY Acad Sci. 2006;  1073 122-137
• 3 Eisenhofer G, Rivers G, Rosas AL, Quezado Z, Manger WM, Pacak K. Adverse drug reactions in patients with phaechromocytoma: incidence, prevention and management.  Drug Saf. 2007;  30 1030-1062
• 4 Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma.  J Urol. 1992;  147 1-10
• 5 Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.  J Clin Endocrinol Metab. 2000;  85 637-644
• 6 Manger WM. An overview of pheochromocytoma: history, current concepts, vagaries, and diagnostic challenges.  Ann N Y Acad Sci. 2006;  1073 1-20
• 7 Wilkinson DJ, Thompson JM, Lambert GW, Jennings GL, Schwarz RG, Jefferys D, Turner AG, Esler MD. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.  Arch Gen Psychiatry. 1998;  55 511-520
• 8 Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM. The diagnosis and treatment of baroreflex failure.  N Engl J Med. 1993;  329 1449-1455
• 9 Manger WM. Baroreflex failure – a diagnostic challenge.  N Engl J Med. 1993;  329 1494-1495
• 10 Whitman  3rd  HH, Fishman EK, Oberg K, Wildman JM, Long AL. Catecholamine-secreting metastatic carcinoid as differential diagnosis in pheochromocytoma: clinical, laboratory, and imaging clues in the search for the lurking neuroendocrine tumor (NET).  Ann N Y Acad Sci. 2006;  1073 59-78
• 11 Stewart JM. Chronic orthostatic intolerance and the postural tachycardia syndrome (POTS).  J Pediatr. 2004;  145 725-730
• 12 Hoy LJ, Emery M, Wedzicha JA, Davison AG, Chew SL, Monson JP, Metcalfe KA. Obstructive sleep apnea presenting as pseudopheochromocytoma: a case report.  J Clin Endocrinol Metab. 2004;  89 2033-2038
• 13 Bergland BE. Pheochromocytoma presenting as shock.  Am J Emerg Med. 1989;  7 44-48
• 14 Newell KA, Prinz RA, Pickleman J, Braithwaite S, Brooks M, Karson TH, Glisson S. Pheochromocytoma multisystem crisis: a surgical emergency.  Arch Surg. 1988;  123 956-959
• 15 Pochedly C. Neuroblastoma. Acton, Massachusetts: Publishing Sciences Group 1976: 314
• 16 Eisenhofer G, Huysmans F, Pacak K, Walther MM, Sweep FCGT, Lenders JWM. Plasma metanephrines in renal failure.  Kidney Int. 2005;  67 668-677
• 17 Sharabi Y, Goldstein DS, Bentho O, Saleem A, Pechnik S, Geraci MF, Holmes C, Pacak K, Eisenhofer G. Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma.  J Hyperten. 2007;  25 2286-2295
• 18 Harper MA, Murnaghan GA, Kennedy L, Hadden DR, Atkinson AB. Phaeochromocytoma in pregnancy. Five cases and a review of the literature.  Br J Obstet Gynaecol. 1989;  96 594-606
• 19 Ahlawat SK, Jain S, Kumari S, Varma S, Sharma BK. Pheochromocytoma associated with pregnancy: case report and review of the literature.  Obstet Gynecol Surv. 1999;  54 728-737
• 20 Manger WM. The vagaries of pheochromocytoma.  Am J Hyperten. 2005;  18 1266-1270

Correspondence