Ischemic Colitis: An Uncommon Manifestation of Pheochromocytoma

By Szmulowicz, Ursula M Savoie, Lisa M

Pheochromocytoma are rare neuroectodermal tumors, responsible for less than 1 per cent of cases of hypertension. The protean manifestations of pheochromocytomas arise from the effects of catecholamine hypersecretion upon alpha and beta receptors. The lesion may infrequently present with gastrointestinal complaints ranging from constipation and nausea to megacolon and ischemic colitis. Ischemic colitis in association with pheochromocytoma occurs from intense splanchnic vasoconstriction. A case of pheochromocytoma presenting as ischemic colitis is reported. WITH AN INCIDENCE of 0.3 per cent to 0.95 per cent, pheochromocytomas represent a rare neuroectodermal tumor of chromaffin cell origin, the treatment of which is entirely surgical.1 Most pheochromocytomas appear within the abdomen, with 85 per cent to 95 per cent of such lesions found in the adrenal medulla.1 These adrenal gland tumors produce norepinephrine and its by-product, epinephrine.2 The symptoms of pheochromocytomas are primarily attributable to catecholamine hypersecretion, with epinephrine and norepinephrine acting upon a and a receptors.3 The majority of these patients, 90 per cent to 100 per cent, suffer from hypertension; in one-third of cases, the elevated blood pressure is paroxysmal.2 The classic triad of symptoms includes severe headaches, diaphoresis, and palpitations.4 Yet, pheochromocytomas have a myriad of presentations ranging from anxiety to shock.2,5 The tumor may mimic other diseases, including diabetes mellitus and hyperthyroidism.6 Moreover, patients have reported abdominal complaints arising from the pheochromocytoma: nausea and vomiting (18.6%), abdominal pain (13.5%), and constipation (10.6%) were reported in one series.1 In addition, rare cases have been recounted of patients appearing with gastrointestinal bleeding, pseudo-obstruction, and ischemic colitis.6,8 In particular, colonie ischemia is ascribed to catecholamine-mediated vasospasm via a-1 receptors.9,10

Case Report

On July 12, 2005, a 66-year-old steroid-dependent woman presented with complaints of severe left upper quadrant pain and nausea. The patient had been treated for several days before her hospital visit for a urinary tract infection with oral antibiotics. An examination revealed an uncomfortable patient with a fever of 38.20C, a systolic blood pressure ranging from 105 to 150 mm Hg, and tachycardia. Palpation of her abdomen demonstrated left upper quadrant tenderness. Her white blood cell count was elevated at 19,640. A CT scan revealed a 10.3 ? 6.1-cm thick-walled structure containing air and fecal debris in the location of the splenic flexure with surrounding pericolonic inflammation, consistent with an area of ischemic colon (Fig. 1). Incidentally, a right-sided 3.8 x 2.7-cm majgs was noted posterior to the inferior vena cava at the level of the right renal hilum (Fig. 2). During an exploratory laparotomy, the colon at the splenic flexure was found to be completely gangrenous. A partial left colectomy, including the splenic flexure, was performed and a transverse colostomy was created. The patient experienced no lability in her blood pressure during the procedure. Ultimately, the pathologic examination demonstrated transmural ischemie necrosis without significant vascular changes. By postoperative Day 15, the patient was transferred to subacute care. Her blood pressure, which attained highs of 152 to 200/91 to 100 mm Hg, was well controlled by lisinopril and metoprolol.

Three days after her discharge to subacute care, the patient was admitted to the intensive care unit with fever and hypotension. Although no source for this septic picture was identified, she improved with broad-spectrum antibiotics, stress-dose steroids, and intravenous hydration. The issue of the right paracaval mass was addressed during this hospitalization. Approximately 19 years ago, the patient had been evaluated for a pheochromocytoma because of symptoms of palpitations, panic attacks, headache, and diaphoresis in addition to hypertension. At the time, the diagnosis was discounted because no tumor was located despite thorough imaging. Thus, the adrenaline excess demonstrated on laboratory studies was ascribed to her medications. Over the years, the hypertension was well controlled with only the angiotensin-converting enzyme inhibitor, fosinopril. However, the symptoms did persist, requiring the use of effexor, clonazepam, and trazadone. Only during the initial hospital admission, with the CT finding of a right paracaval mass, was the diagnosis of pheochromocytoma again entertained and the patient reassessed for biochemical evidence of catecholamine excess. The plasma-free normetanephrine and the plasma norepinephrine were elevated at 4.24 nmol/L (normal < 1.09 nmoFL) and 3970 pg/mL (normal < 420 pg/mL), respectively. Also, a 24-hour urine study uncovered a metanephrine of 1541 [mu]g/g (normal < 600 [mu]g/g) and a vanillylmandelic acid of 8.8 mg (normal 1.8-6.7 mg). Additionally, a CT/positron emission tomography scan revealed moderately increased uptake of 18-fluorodeoxyglucose in the location of the right paracaval mass. The patient was placed on phenoxybenzamine in preparation for the resection of the suspected right-sided pheochromocytoma, scheduled at a university hospital for October 25, 2005.

FIG. 1. Noncontrasted abdominal CT scan demonstrating the left upper quadrant “abscess.”

FIG. 2. Noncontrasted abdominal CT scan with right paracaval mass.

On October 20, 2005, the patient returned to this facility from subacute care complaining of abdominal pain, nausea, and vomiting. Her vital signs were notable for a fever of 38.4[degrees]C, a blood pressure of 156/100 mm Hg, and tachycardia. Her abdomen was firm and diffusely tender with a mass palpable over the midepigastrum. The initial white blood cell count was 18,100. A plain radiograph of the abdomen revealed a markedly dilated, stool-filled proximal colon and no free air. Upon exploration, the right and transverse colon were found to be massively distended as well as frankly gangrenous. An extended right hemicolectomy and end ileostomy were completed. The patient experienced no hypertensive episodes during the procedure. The pathologic examination demonstrated transmural necrosis and a segmentai narrowing within the right colon; no vascular lesions were identified. Two months later, the patient was discharged to a rehabilitation facility. Without any antihypertensive medications, the patient maintained a systolic blood pressure of 130 to 160 mm Hg with occasional paroxysms of higher pressures associated with diaphoresis. Resection of the right-sided pheochromocytoma took place at the university center on March 13, 2006, via a laparoscopic right flank approach. Before the division of the right adrenal vein, the patient experienced markedly elevated blood pressures. The pathology report described a 4.3 x 3.4 x 1.6-cm well- circumscribed, yellow, focally hemorrhagic mass that, on microscopic examination, was a pheochromocytoma.

Discussion

Ischemic colitis in association with pheochromocytoma has rarely been reported in the literature. These cases were identified by a Medline search using the terms pheochromocytoma, ischemie colitis, ischemia, and colon. Eleven reports of colonie ischemia were identified in the English literature10-19 (Table 1). TThe combined mortality rate of the now 12 patients with these two simultaneous processes is 41.6 per cent, underscoring the dismal prognosis. Although ischemia precipitated by pheochromocytoma may affect the small and large bowel, the colon is more predisposed to such episodes.14 Brown and Borowsky10 reported the case of a 37-year-old woman with a history of right adrenalectomy for a pheochromocytoma who presented with chest pain, nausea, vomiting, and severe hypertension. During the resection of a segment of the massively dilated colon, metastatic deposits of pheochromocytoma were discovered. Five hours later, the distal colon, now ischemic, was removed at relaparotomy. An eventual autopsy uncovered ischemia of the right colon and rectosigmoid with patent mesenteric vessels. Microscopic examination of the colon demonstrated slightly thickened arteriolar walls without evidence of occlusive endarteritis. The authors proposed that the colonie ischemia arose from the hypersecretion of vasoconstrictor substances from the metastatic pheochromocytoma, resulting in an increase in mesenteric vascular resistance even in the absence of large vessel occlusive disease.10

An early report of two cases of pheochromocytoma in association with small intestinal ischemia from Brown et al.8 implicated a proliferative and occlusive endarteritis of the small mesenteric vessels in the ischemie process. To investigate this phenomenon further, Brown and colleagues administered varying doses of 1- norepinephrine to dogs to reproduce the intestinal lesions. Only the dogs that received the continuous infusion for the longest periods exhibited intimai proliferation with narrowing and even obliteration of the arterioles.8 Thus, the finding of occlusive small vessel endarteritis was ascribed to changes consistent with chronic hypertension. Such lesions are also evident in 9 per cent to 15 per cent of patients with severe chronic hypertension upon postmortem examination.20 It was concluded that gastrointestinal ischemia secondary to pheochromocytoma may occur in the presence or absence of such small vessel changes.10- 13> 16 TABLE 1. Summary of cases of Ischemic Colitis in Association with Pheochromocytoma

Several series have addressed the tumor characteristics that may contribute to colonie ischemia. Grossman et al.11 recorded the case of a 58-year-old woman with a history of labile hypertension who presented with severe abdominal pain. The diaphoretic patient was hypotensive and tachycardie, with a rigid abdomen. A left adrenal mass was located on angiography; the study also showed mesenteric arterial spasm. At laparotomy, a hemorrhagic adrenal mass was resected, as was the infarcted right colon. The authors indicated that hemorrhage within the pheochromocytoma may have induced a greater release of catecholamines than normal, resulting in the colonie ischemia.11″13 In addition, several other studies have correlated larger masses (over 70 g) with the development of the gastrointestinal symptoms of pheochromocytomas.7’20

Similar to the patients in the previous studies, the patient detailed in the present report developed ischemie colitis in association with a newly discovered pheochromocytoma. Upon her presentation to this hospital, the patient was initially believed to have developed colonie ischemia from hypotension arising from adrenal insufficiency and a urinary tract infection. However, in light of the later diagnosis of pheochromocytoma, an underlying catecholamine-induced mesenteric vasoconstriction may have been further compounded by these factors. Morris and McDevitt14 suggest that a chronic state of mesenteric vasoconstriction may exist in these patients with pheochromocytoma; an added factor such as relative hypotension may precipitate ischemia in the susceptible colon. The treatment of pheochromocytoma rests on surgical resection. Several authors recommend prompt excision of such tumors in the presence of gastrointestinal symptoms because of the possibility of developing coIonic ischemia.10, 12 As such, a timelier resection of the tumor in this patient may have obviated the need for the second laparotomy.

Conclusion

Although rare, pheochromocytoma are potentially lethal tumors with a myriad of presentations attributable to catecholamine hypersecretion. Although hypertension is the typical manifestation, the tumor may produce such abdominal complaints as constipation, pain, and vomiting. Infrequently, patients demonstrate gastrointestinal complications such as ischemie colitis. This complication of pheochromocytoma is ascribed to catecholamine- induced splanchnic vasoconstriction in the absence of large vessel occlusion. This may be especially precipitated by a large or hemorrhagic tumor. Small vessel lesions may occasionally be present but merely reflect chronic hypertensive changes. Ultimately, the management of gangrenous ischemie colitis as well as pheochromocytoma requires surgery. The presence of gastrointestinal symptoms in a patient with a known pheochromocytoma should suggest the possibility of colonie ischemia and compel a prompt resection of the tumor. Despite timely intervention, the mortality for colonie ischemia in association with pheochromocytoma remains high.

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URSULA M. SZMULOWICZ, M.D., LISA M. SAVOIE, M.D.

From the Greater Baltimore Medical Center, Towson, Maryland

Address correspondence and reprint requests to Ursula M. Szmulowiez, 30800 SiJktree Lane, Westlake, OH 44145.

Copyright Southeastern Surgical Congress Apr 2007

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