Title: Pheochromocytoma in a Patient With End-Stage Renal Disease
Abstract: Pheochromocytoma is a rare tumor. To our knowledge only 15 cases have been reported in patients with end-stage renal disease (ESRD). We describe a 46-year-old woman with ESRD and a history of paroxysmal and difficult-to-control hypertension. During anesthesia for a surgical procedure, the patient experienced blood pressure lability with systolic blood pressures ranging from 76 to 360 mm Hg. Serum catecholamine concentrations were 2698 pg/mL (reference value, <750 pg/mL) for norepinephrine, 33 pg/mL (<110 pg/mL) for epinephrine, and 55 pg/mL (<30 pg/mL) for dopamine. The concentrations of plasma metanephrines were 6.84 nmol/L (<0.50 nmol/L) for metanephrine and 14.64 nmol/L (<0.90 nmol/L) for normetanephrine. Abdominal computed tomography showed a right-sided, 4-cm mass posterior to the infra-hepatic inferior vena cava. Following blood pressure control with a- and β-adrenergic blockade, the mass was removed. Pathologic examination demonstrated the mass was a pheochromocytoma. The maximum postoperative systolic blood pressure was 160 mm Hg. Postoperative plasma normetanephrine concentration was 2.80 nmol/L, and metanephrine was obscured by interfering substances. This case report and literature review emphasizes the difficulty in diagnosing pheochromocytomas in patients with ESRD despite the myriad of available diagnostic tests. Pheochromocytoma is a rare tumor. To our knowledge only 15 cases have been reported in patients with end-stage renal disease (ESRD). We describe a 46-year-old woman with ESRD and a history of paroxysmal and difficult-to-control hypertension. During anesthesia for a surgical procedure, the patient experienced blood pressure lability with systolic blood pressures ranging from 76 to 360 mm Hg. Serum catecholamine concentrations were 2698 pg/mL (reference value, <750 pg/mL) for norepinephrine, 33 pg/mL (<110 pg/mL) for epinephrine, and 55 pg/mL (<30 pg/mL) for dopamine. The concentrations of plasma metanephrines were 6.84 nmol/L (<0.50 nmol/L) for metanephrine and 14.64 nmol/L (<0.90 nmol/L) for normetanephrine. Abdominal computed tomography showed a right-sided, 4-cm mass posterior to the infra-hepatic inferior vena cava. Following blood pressure control with a- and β-adrenergic blockade, the mass was removed. Pathologic examination demonstrated the mass was a pheochromocytoma. The maximum postoperative systolic blood pressure was 160 mm Hg. Postoperative plasma normetanephrine concentration was 2.80 nmol/L, and metanephrine was obscured by interfering substances. This case report and literature review emphasizes the difficulty in diagnosing pheochromocytomas in patients with ESRD despite the myriad of available diagnostic tests. Pheochromocytoma is a rare tumor derived from chromaffin cells of the sympathetic nervous system. The annual incidence of this catecholamine-producing tumor is estimated at between 2 and 8 cases per 1 million people in the general population1Stenstrom G Svardsudd K Pheochromocytoma in Sweden 1958–1981: an analysis of the National Cancer Registry Data.Acta Med Scand. 1986; 220: 225-232Crossref PubMed Scopus (222) Google Scholar and 0.5 per 1000 hypertensive patients.2Beard CM Sheps SG Kurland LT Carney JA Lie JT Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979.Mayo Clin Proc. 1983; 58: 802-804PubMed Google Scholar Diagnosing these tumors is important because they represent a curable form of hypertension, 10% are malignant, and paroxysms can be associated with severe morbidity and mortality.3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar In patients with end-stage renal disease (ESRD), the diagnosis is complicated by the patient's anuric state, making traditional testing difficult or unreliable. We describe a patient with pheochromocytoma whose diagnosis was complicated by ESRD. A 46-year-old woman with ESRD was transferred to our hospital because of an infection at the site of a previously thrombosed polytetrafluoroethylene (PTFE) graft in her left brachial area. The infection persisted for 2 weeks prior to her transfer despite treatment with intravenous vancomycin. Her medical history was contributory. Hypertension was first noted when she was in her early 20s during a pregnancy in which she also had proteinuria. At the age of 25 years, she underwent a right nephrectomy for chronic pyelonephritis and sepsis in a congenitally small kidney. At the age of 35 years, she had a cerebrovascular accident (CVA), followed at the age of 40 years by a CVA in the right middle cerebral artery distribution, resulting in left-sided hemiparalysis. At the age of 42 years type 2 diabetes mellitus developed. At 45 years, ESRD developed, requiring long-term hemodialysis (HD), and she was anuric. A PTFE graft was placed, but it quickly thrombosed. Her blood pressure (BP) was 200/110 mm Hg after thrombectomy. One month later she had a generalized tonic clonic seizure, after which her BP was 278/108 mm Hg. Treatment included amlodipine and metoprolol. Several weeks later she was admitted to the hospital for dyspnea. Her BP was 190/110 mm Hg at the time, and treatment with captopril was added. A computed tomographic (CT) scan, done because she complained of abdominal pain, revealed a right-sided, 4-cm mass posterior to the infrahepatic inferior vena cava (Figure 1). Anuria prevented routine urinary screening studies for pheochromocytoma. Serum cat-echolamine measurements revealed norepinephrine level of 2698 pg/mL (reference range, 70–750 pg/mL); epinephrine, 33 pg/mL (0–110 pg/mL); and dopamine, 55 pg/mL (<30 pg/mL). Iodine 123 meta-iodobenzylguanidine (123I-MIBG) scintigraphy was not performed because a family member who had power of attorney refused consent. Despite the mass noted on CT scanning, the abnormal serum catecholamine concentrations, and the attempt to perform 123I-MIBG scanning, pheochromocytoma was not recorded in the medical record as having been considered in the differential diagnosis. Additionally, the patient's medical record contained no mention of specific follow-up plans for these abnormal test results. On admission to our service, her BP was 220/110 mm Hg despite treatment with amlodipine, 10 mg twice a day; metoprolol, 100 mg twice a day; and hydralazine, 25 mg 3 times a day. Her left brachial area was infected as evidenced by purulent drainage. We diagnosed an abscess surrounding the PTFE graft, and vascular surgeons were consulted to urgently remove the graft. Intraoperative BPs were labile, ranging from 76 to 360 mm Hg systolic and 50 to 160 mm Hg diastolic. Postoperative treatment in the intensive care unit consisted of nitro-prusside sodium, labetalol, hydralazine, and phentolamine. Her BPs ranged from 105 to 205 mm Hg systolic and 55 to 95 mm Hg diastolic. This BP lability combined with her prior abnormal diagnostic test results brought the possibility of a pheochromocytoma to the forefront of the differential diagnosis. Consequently, plasma metanephrine concentrations were increased: metanephrine, 6.84 nmol/L (<0.50 nmol/L) and normetanephrine, 14.64 nmol/L (<0.90 nmol/L). Phenoxybenzamine was given for 10 days to achieve complete a-adrenergic blockade, after which a right adrenalectomy was performed without complications. The pathologic examination showed a multinodular pheochromocytoma measuring 4.8 × 4.5 × 2.7 cm. Her postoperative course was unremarkable, with a maximum systolic BP of 160 mm Hg. Repeat plasma metanephrine determination showed normetanephrine to be 2.80 nmol/L; the metanephrine level was obscured by interfering substances. Treatment with phenoxybenzamine was stopped, and the patient was discharged receiving a regimen of amlodipine, 10 mg twice a day; metoprolol, 100 mg every morning and 150 mg every evening; and hydralazine, 25 mg 3 times a day. Three months postoperatively she had persistent hypertension that required treatment with medication, although the hypertension was no longer paroxysmal. Repeat plasma normetanephrine determination showed a concentration of 2.28 nmol/L, and metanephrine was again obscured by an interfering substance. Pheochromocytomas are rare tumors, yet once suspected, diagnosis is relatively straightforward. However, in patients with ESRD, the diagnosis of pheochromocytoma may be difficult. A MEDLINE search (1966-mid 2000) resulted in 15 case reports of pheochromocytoma in ESRD.4Vila R Miguel E Martinez V Diaz MC Nieto J Potau N Anesthesia for pheochromocytoma in a surgically anephric child.Anesth Analg. 1997; 85: 1042-1044PubMed Google Scholar, 5Asaka S Takayama Y Tagawa S et al.Pheochromocytoma in a long-term hemodialysis patient, discovered as an adrenal incidentaloma.Intern Med. 1997; 36: 403-407Crossref PubMed Scopus (11) Google Scholar, 6Box JC Braithwaite MD Duncan T Lucas G Pheochromocytoma, chronic renal insufficiency, and hemodialysis: a combination leading to a diagnostic and therapeutic dilemma.Am Surg. 1997; 63: 314-316PubMed Google Scholar, 7Sagara M Arimura S Kammura Y Yoshimura N Anesthesia for a patient with pheochromocytoma associated with chronic renal failure [in Japanese].Masui. 1996; 45: 1256-1259PubMed Google Scholar, 8Ferrante A Bellantone R Barbarino A et al.Paroxystic hypertension in a long-term hemodialyzed patient: successful adrenalectomy for a dopamine-producing pheochromocytoma.J Endocrinol Invest. 1995; 18: 656-662PubMed Google Scholar, 9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar, 10Sollazzi L Perilli V Crea MA et al.Anesthetic management of pheochromocytoma in a long term hemodialysed patient.Acta Anaesthesiol Belg. 1994; 45: 13-17PubMed Google Scholar, 11Ligtenberg G Blankestijn PJ Koomans HA Phaeochromocytoma in a long-term haemodialysis patient: diagnosis and management.Nephrol Dial Transplant. 1993; 8: 1172-1173PubMed Google Scholar, 12Misawa T Shibasaki T Toshima R et al.A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient.Nephron. 1993; 64: 443-446Crossref PubMed Scopus (18) Google Scholar, 13Chauveau D Martinez F Houhou S Grünfeld JP Malignant hypertension secondary to pheochromocytoma in a hemodialyzed patient.Am J Kidney Dis. 1993; 21: 52-53PubMed Scopus (15) Google Scholar, 14Yuasa S Bandai H Yura T et al.Successful resection of pheochromocytoma in a hemodialysis patient.Am J Nephrol. 1992; 12: 111-115Crossref PubMed Scopus (13) Google Scholar, 15Fillastre JP Godin M Moulin B et al.Pheochromocytoma in a renal failure patient treated by hemodialysis [letter].Am J Kidney Dis. 1992; 19: 94-95PubMed Scopus (7) Google Scholar, 16Yver L Jaulin JP Nanhuck H Rivet P Pheochromocytoma in a long-term hemodialysis patient.Am J Kidney Dis. 1991; 18: 276-277Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 17Yamamoto T Iizima K Mizuguchi T Anesthesia for a patient with pheochromocytoma associated with chronic renal failure [in Japanese].Masui. 1989; 38: 805-808PubMed Google Scholar, 18Bommer J Unexplained hypertension in a previously normotensive dialysis patient: diagnosis: pheochromocytoma.Nephrol Dial Transplant. 2000; 15: 1705-1706Crossref PubMed Scopus (6) Google Scholar The usual screening test involving a 24-hour urinary collection for metanephrines and catecholamines is useless in anuric/oliguric patients. Clouding the issue is the fact that many patients with ESRD are hypertensive due to their renal disease. Although measurement of serum catecholamine concentrations would seem logical, patients undergoing long-term HD have increased levels compared with the controls. Furthermore, no definitive reference ranges for serum catecholamine concentrations have been established for patients receiving long-term HD.9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar Given these obstacles, the diagnosis must still begin with a thorough history and physical examination. A classic presentation can be remembered as “the 5 P's”-pressure, pain, perspiration, palpitation, and pallor. Other symptoms and signs seen in patients with pheochromocytoma include nausea, dyspnea, anxiety, tremor, weakness, exhaustion, constipation, retinopathy, weight loss, orthostatic hypotension, congestive heart failure, hyperglycemia, and painless hematuria.3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar A thorough review of medications is required. Drugs known to give false-positive results in catecholamine and catecholamine metabolite testing include labetalol, sotalol, tricyclic antidepressants, benzodiazepines, buspirone, amphetamines, ethanol, methyldopa, levodopa, and catecholamine-containing drugs (over-the-counter cold remedies and decongestants).19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar, 20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Physical stress and obstructive sleep apnea also cause false-positive results. Laboratory and radiographic diagnostic tests are used to confirm the diagnosis of pheochromocytoma before any tissue is obtained. Urinary screening is impossible in patients receiving long-term HD, unlike patients with normal kidney function. Serum catecholamine determinations provide the only useful diagnostic information in ESRD patients. One report9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar evaluated the literature comparing cat-echolamine levels in controls and in patients receiving long-term HD. The authors found the norepinephrine concentration was consistently elevated in the long-term HD group, but never more than 3-fold. The dopamine level was increased approximately 2-fold in the long-term HD group. Epinephrine, however, was not significantly different in the 2 groups. Looking at pheochromocytoma in patients receiving long-term HD, this same review noted epinephrine and norepinephrine concentrations to be at least 3.3-fold higher than normal values in 4 of 7 and 5 of 7 case reports, respectively.9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar Any rise in catecholamine concentrations higher than 3-fold above normal in patients receiving long-term HD suggests pheochromocytoma.19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar Our patient's catecholamine levels were consistent with these findings; notably, the norepinephrine level was 3.6-fold higher than our laboratory's upper limit of normal. Lenders et al21Lenders JW Keiser HR Goldstein DS et al.Plasma metanephrines in the diagnosis of pheochromocytoma.Ann Intern Med. 1995; 123: 101-109Crossref PubMed Scopus (219) Google Scholar evaluated the plasma metanephrines in 52 patients with pheochromocytoma and found the test to have 100% sensitivity and 100% negative predictive value for this diagnosis. However, none of these patients had ESRD. A group of Swiss investigators22Marini M Fathi M Vallotton M Dosage des métanéphrines sériques pour le diagnostic du phéochromocytome [Serummetanephrines determination for the diagnosis of pheochromocytoma].Ann Endocrinol (Paris). 1994; 54: 337-342PubMed Google Scholar had comparable results with similar groups of patients. However, their study also compared pheochromocytoma patients with ESRD patients receiving long-term HD but without pheochromocytoma. They found that plasma metanephrine levels did not distinguish between pheochromocytoma patients and ESRD patients requiring long-term HD. Therefore, elevated plasma metanephrine concentrations in our patient were most likely a result of both long-term HD and pheochromocytoma. Consequently, it is impossible to determine whether this patient's persistently elevated normetanephrine level after surgery was due to continued HD or persistence of pheochromocytoma. Other biochemical modalities are not useful in the diagnosis of pheochromocytoma in patients receiving long-term HD. Investigators studied serum chromogranin A in the diagnosis of pheochromocytoma but demonstrated its low diagnostic specificity for this disease in patients with impaired renal function.23Canale MP Bravo EL Diagnostic specificity of serum chromogranin-A for pheochromocytoma in patients with renal dysfunction.J Clin Endocrinol Metab. 1994; 78: 1139-1144Crossref PubMed Scopus (58) Google Scholar Plasma neuropeptide Y levels are higher only in pheochromocytoma patients with intra-adrenal disease. However, this test is not useful because no study has demonstrated its role in diagnosing tumors undetectable with conventional methods.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Although used only rarely, various pharmacologic studies can assist with the diagnosis of pheochromocytoma. Clonidine or pentolinium (a ganglionic-blocking agent) suppression testing decreases catecholamine levels in patients with essential hypertension but not in those with pheochromocytoma; however, some patients without either condition also do not suppress.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar It is unclear how long-term HD affects this test. a-Adrenergic blockade with phentolamine testing is often suggestive of pheochromocytoma, but false-positive results are frequently seen in patients with renal failure. Provocative testing with glucagon, histamine, or tyramine is rarely used, given the risks of hypertensive crises and high rates of false-negative results.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Confirming the diagnosis of pheochromocytoma with biochemical testing should always precede radiographic localization of the tumor. A study that compared various imaging modalities to help localize pheochromocytomas demonstrated an overall sensitivity of 98% for magnetic resonance imaging (MRI), 89% for CT, and 81% for 131IMIBG.24Jalil ND Pattou FN Combemale F French Association of Surgery (AFC), French Association of Endocrine Surgeons (AFCE). et al.Effectiveness and limits of preoperative imaging studies for the localisation of pheochromocytomas and paragangliomas: a review of 282 cases.Eur J Surg. 1998; 164: 23-28Crossref PubMed Scopus (135) Google Scholar This study demonstrates that MRI of the adrenals and abdomen is the test of choice, but CT is acceptable. An extra-adrenal location occurs in approximately 10% of all patients with pheochromocytoma. Therefore, a directed investigation of areas where extra-adrenal pheochromocytomas commonly occur should be done when the adrenals appear normal on radiologic testing (Figure 2). Scintigraphy with 123I-MIBG, a radiolabeled agent that localizes in catecholamine-secreting tumors,3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar has excellent specificity (95%-100%).26Pacak K Linhan WM Eisenhofer G Walther MM Goldstein DS Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma.Ann Intern Med. 2001; 134: 315-329Crossref PubMed Scopus (482) Google Scholar This test is indicated if MRI and CT are negative or if the tumor is extra-adrenal.3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar Other localization tools can also be used. Newbould et al27Newbould EC Ross GA Dacie JE Bouloux PM Besser GM Grossman A The use of venous catheterization in the diagnosis and localization of bilateral phaeochromocytomas.Clin Endocrinol (Oxf). 1991; 35: 55-59Crossref PubMed Scopus (27) Google Scholar demonstrated that selective venous sampling of catecholamines gave a sensitivity of 100% and suggested a similar specificity. All their positive findings were confirmed histologically. Shulkin et al28Shulkin BL Wieland DM Schwaiger M et al.PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma.J Nucl Med. 1992; 33: 1125-1131PubMed Google Scholar studied positron emission tomography in conjunction with carbon 11 hydroxyephedrine. They demonstrated this imaging modality to be positive in 9 of 10 patients with known or suspected pheochromocytoma, for a sensitivity of 90%. Initial results with 6-[18F]fluorodopamine positron emission tomography are also promising.29Pacak K Eisenhofer G Carrasquillo JA Chen CC Li ST Goldstein DS 6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma.Hypertension. 2001; 38: 6-8Crossref PubMed Scopus (181) Google Scholar Somatostatin receptor scintigraphy with indium 111-labeled octreotide detected 12 of 14 adrenal pheochromocytomas in a study by Krenning et al.30Krenning EP Kwekkeboom DJ Bakker WH et al.Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients.Eur J Nucl Med. 1993; 20: 716-731Crossref PubMed Scopus (1425) Google Scholar Even though this imaging method has 86% sensitivity, it gives no information about whether the pheochromocytoma is benign or malignant.31Tenenbaum F Lumbroso J Schlumberger M et al.Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma.J Nucl Med. 1995; 36: 1-6PubMed Google Scholar Biochemical and radiographic diagnosis should always precede any tissue diagnosis. With an unsuspected pheochromocytoma, percutaneous biopsy can lead to a hypertensive crisis or death.32McCorkell SJ Niles NL Fine-needle aspiration of catecholamine-producing adrenal masses: a possibly fatal mistake.AJR Am J Roentgenol. 1985; 145: 113-114Crossref PubMed Scopus (114) Google Scholar, 33Casola G Nicolet V vanSonnenberg E et al.Unsuspected pheochromocytoma: risk of blood-pressure alterations during percutaneous adrenal biopsy.Radiology. 1986; 159: 733-735PubMed Google Scholar, 34Baguet JP Hammer L Tremel F Mangin L Mallion JM Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation.J Hum Hypertens. 2001; 15: 209-211Crossref PubMed Scopus (23) Google Scholar Complication rates range from 8% to 12.7% overall. These include bleeding, pneumothorax, pain, abdominal discomfort, acute pancreatitis, fever, bacteremia, and nausea. However, when just major complications are analyzed (ie, those requiring hospitalization or therapeutic intervention), the rate is approximately 3%.35Korobkin M Francis IR Imaging of adrenal masses.Urol Clin North Am. 1997; 24: 603-622Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Treatment of pheochromocytomas in patients with ESRD follows the same principles as that for patients with normal renal function. Complete a-adrenergic blockade is the cornerstone of preoperative medical management. Phenoxybenzamine, a nonselective a-adrenergic blocking agent, is the treatment of choice. Treatment is initiated with 10 mg every 12 hours, increasing the dose by 10 mg every 2 to 3 days until BP is controlled. Usual daily doses range from 40 to 80 mg but can be as high as 200 mg.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Treatment should extend at least 7 to 10 days preoperatively.3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar, 20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Selective a1-antagonists (doxazosin, prazosin, and terazosin) are not routinely used preoperatively because of incomplete a-adrenergic blockade. However, if long-term treatment is needed (ie, for metastatic pheochromocytoma), these may be more advantageous given their decreased adverse effect profile.19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar If further antihypertensive medication is required, β-adrenergic antagonists, calcium channel blockers, and nitrates are useful. β-Blockade should be used only after 7 days of a-blockade to prevent paradoxical hypertension caused by any unopposed a-adrenergic stimulation.3Young Jr, WF Pheochromocytoma: issues in diagnosis and treatment.Compr Ther. 1997; 23: 319-326PubMed Google Scholar The calcium channel antagonist nicardipine can be given orally or intravenously. Sodium nitroprusside is also effective,19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar but its use is limited to a few days' duration by the development of cyanide toxicity. Definitive therapy for pheochromocytoma is resection by a surgeon and anesthesiologist who have experience with this high-risk procedure.19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar Intraoperative and postoperative hypotension can be minimized if a liberal salt and fluid intake is allowed for several days preoperatively.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Hemodynamic monitoring (arterial and central venous pressures) is essential, and measuring the pulmonary capillary wedge pressure is indicated in patients with heart disease.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Rarely are vasopressors required, especially with adequate a-adrenergic blockade prior to surgery. To confirm complete resection of a pheochromocytoma, urinary catecholamine concentrations and their metabolite levels should be measured 1 to 2 weeks postoperatively and yearly for at least 10 years.19Young Jr, WF Pheochromocytoma and primary aldosteronism: diagnostic approaches.Endocrinol Metab Clin North Am. 1997; 26: 801-827Abstract Full Text Full Text PDF PubMed Google Scholar, 20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Complete resection is indicated by normalization of these values.20Young JB Landsberg L Catecholamines and the adrenal medulla.in: Wilson JD Foster DW Kronenberg HM Larsen PR Williams Textbook of Endocrinology. 9th ed. WB Saunders Co, Philadelphia, Pa1998: 705-716Google Scholar Again, anuria/oliguria complicates this testing in ESRD patients. Four case reports indicate that serum catecholamine concentrations decreased to normal postoperatively in patients with ESRD who were receiving long-term HD.6Box JC Braithwaite MD Duncan T Lucas G Pheochromocytoma, chronic renal insufficiency, and hemodialysis: a combination leading to a diagnostic and therapeutic dilemma.Am Surg. 1997; 63: 314-316PubMed Google Scholar, 8Ferrante A Bellantone R Barbarino A et al.Paroxystic hypertension in a long-term hemodialyzed patient: successful adrenalectomy for a dopamine-producing pheochromocytoma.J Endocrinol Invest. 1995; 18: 656-662PubMed Google Scholar, 9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar, 13Chauveau D Martinez F Houhou S Grünfeld JP Malignant hypertension secondary to pheochromocytoma in a hemodialyzed patient.Am J Kidney Dis. 1993; 21: 52-53PubMed Scopus (15) Google Scholar In 2 of these reports,6Box JC Braithwaite MD Duncan T Lucas G Pheochromocytoma, chronic renal insufficiency, and hemodialysis: a combination leading to a diagnostic and therapeutic dilemma.Am Surg. 1997; 63: 314-316PubMed Google Scholar, 9Stumvoll M Radjaipour M Seif F Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.Am J Nephrol. 1995; 15: 147-151Crossref PubMed Scopus (36) Google Scholar postoperative catecholamine levels were measured at least 7 days after removal of the pheochromocytoma, while it is unclear in the other 2 articles,8Ferrante A Bellantone R Barbarino A et al.Paroxystic hypertension in a long-term hemodialyzed patient: successful adrenalectomy for a dopamine-producing pheochromocytoma.J Endocrinol Invest. 1995; 18: 656-662PubMed Google Scholar, 13Chauveau D Martinez F Houhou S Grünfeld JP Malignant hypertension secondary to pheochromocytoma in a hemodialyzed patient.Am J Kidney Dis. 1993; 21: 52-53PubMed Scopus (15) Google Scholar when the catecholamine levels were measured. In summary, diagnosis of pheochromocytoma is difficult in patients with ESRD who are receiving long-term HD. However, knowing how to make an accurate diagnosis allows adequate treatment and prevention of long-term complications from poorly controlled hypertension.