Improved safety of glucagon testing for pheochromocytoma by prior alpha-receptor blockade. A controlled trial in a patient with a mixed ganglioneuroma/pheochromocytoma

The glucagon stimulation test has been superseded in recent years by the clonidine suppression test because it can provoke dangerous increases in blood pressure in patients with pheochromocytomas. We describe the first patient in whom a pheochromocytoma was diagnosed by a glucagon test, after which the blood pressure (but not the plasma catecholamine) response to a second injection of glucagon was blocked by pretreatment with phenoxybenzamine. After the tumor (which contained both pheochromocytoma and ganglioneuroma tissue) was removed, a third glucagon test result was negative. This experience suggests that patients with normal plasma catecholamine levels who are suspected of harboring a pheochromocytoma may be accurately diagnosed, but potentially dangerous increases in blood pressure may be minimized, by performing the glucagon test after alpha-adrenergic blockade.     

Functional ‘composite’ pheochromocytoma–ganglioneuroma presenting as a pancreatic mass

Pheochromocytomas rarely have ‘composite’ forms in which they demonstrate histologic features of a typical paraganglioma in combination with those of a neural component. Extra-adrenal ‘composite’ pheochromocytomas are distinctly uncommon. We describe herein a unique case of a 34-year-old female patient with type 1 neurofibromatosis who presented with abdominal pain and paroxysmal hypertension. Imaging revealed a pancreatic mass with biliary and pancreatic ductal dilatation and a hormonal assay led to the diagnosis of functional pheochromocytoma. She underwent surgical resection and histopathology revealed a composite paraganglioma–ganglioneuroma. Clinical, biochemical and radiological aspects of this rare tumor and its association with neurofibromatosis and other hereditary cancer syndromes are discussed.     

Central pancreatectomy for a pancreatic ganglioneuroma in a patient with previous neuroblastoma

This is a case presentation of a 28-year-old woman with a mass at thejunction of the neck and the body of the pancreas and a childhood history of a resected adrenal neuroblastoma. A central pancreatectomy was performed in this patient. The pathology revealed a benign ganglio-neuroma. Ganglioneuromas and their association with a neuroblastoma are briefly reviewed. The indications and contraindications for, as well as the advantages and disadvantages of, a central pancreatic resection are discussed.     

A case of undiagnosed pheochromocytoma caused by negative metoclopramide test

Metoclopramide (MCP), a dopamine antagonist, was recently used as the pharmacological test for the diagnosis of pheochromocytoma. There have been no reports involving false negative cases in the MCP test. We experienced a rare case of pheochromocytoma which showed a negative MCP test, and it caused a failure of the diagnosis. A 51-year-old man visited our hospital with a sudden onset of headache and palpitation. Blood pressure was 218/98 mmHg at another hospital. When he came to our hospital, blood pressure returned to normal (120/80 mmHg), and both serum adrenaline (E) and noradrenaline (NE) were within normal limits. A computed tomography, magnetic resonance imaging, and angiography demonstrated a 1.8 x 1.8 cm right adrenal mass. No changes in blood pressure and plasma catecholamine were observed following the injection of 10 mg of MCP. The pathologically resected right adrenal gland contained a typical pheochromocytoma which was 1.0 x 1.0 cm in size and weighed 8 g. The detailed mechanism of the negative MCP test in this case was not known but might be related to the small size of the tumor.     

WDHA syndrome caused by pheochromocytoma: Report of a case

Summary A case in which a pheochromocytoma secreted vasoactive intestinal peptide, causing WDHA syndrome, is reported. The patient, a 43-year-old woman, was seen because of intractable watery diarrhea, hypokalemia and weight loss. She was found to have a mass in the right adrenal area. Preoperatively, vasoactive intestinal peptide levels were elevated, and the diagnosis of WDHA syndrome was entertained. Exploratory laparotomy revealed a tumor of the right adrenal gland, measuring 15×15 cm, which was resected. Histologic examination revealed it to be a pheochromocytoma. Postoperatively, vasoactive intestinal peptide returned to normal. The patient had complete remission of symptoms, and has remained well since. Division of General Surgery.     

Expression of melanin-concentrating hormone receptor messenger ribonucleic acid in tumor tissues of pheochromocytoma, ganglioneuroblastoma, and neuroblastoma

Expression of melanin-concentrating hormone (MCH) receptor messenger ribonucleic acid (mRNA) was studied by RT-PCR and Northern blot analysis in human brain; pituitary; adrenal glands; tumor tissues of adrenal tumors, ganglioneuroblastomas, and neuroblastomas; and various cultured tumor cell lines. RT-PCR analysis showed that MCH receptor mRNA was widely expressed in brain tissues, pituitary, normal portions of adrenal glands (cortex and medulla), tumor tissues of adrenocortical tumors (12 of 13 cases), pheochromocytoma (all 7 cases), ganglioneuroblastoma (1 case), neuroblastoma (all 5 cases), and various cultured tumor cell lines (6 of 7 cell lines), including 2 neuroblastoma cell lines. Northern blot analysis showed the expression of MCH receptor mRNA ( approximately 2.4 kb) only in the tumor tissues of 5 pheochromocytomas, 1 ganglioneuroblastoma, and 4 neuroblastomas, indicating that the expression levels of MCH receptor mRNA are much higher in these tumors than in the other tissues. These findings raised the possibility that MCH or MCH-like peptides may be related to the pathophysiology of these neural crest-derived tumors.     

Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma

We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A) associated with a rare skin disease primary cutaneous lichen amyloidosis and discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail, and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34-yr-old female. The presence of composite tumor of pheochromocytoma and ganglioneuroma arising in the adrenal glands has been described previously in MEN2A and in sporadic cases. The patient displayed classical signs and symptoms of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed tomography revealed multiple mass lesions in both adrenal glands. It also showed a large heterogeneous mass that clearly discriminated from right adrenal gland in retroperitoneal location. After surgical exploration, both adrenal glands and the suspicious mass in pancreatic tail were removed successfully together with subtotal resection of the retroperitoneal tumor. Histopathologic examinations confirmed the presence of pheochromocytoma in both adrenal glands as well as pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic and biochemical evidence of pheochromocytoma subsided after the operation. Further evaluation for medullary thyroid carcinoma and primary hyperparathyroidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene revealed a missense point mutation at position 634 in exon 11, which gives rise to the substitution of a cysteine codon with a tyrosine residue.     

Inverted Takotsubo contractile pattern caused by pheochromocytoma with tall upright T-waves, but not typical deep T-wave inversion

We describe a 36-year-old woman with inverted Takotsubo cardiomyopathy caused by pheochromocytoma crisis. In the acute phase, her electrocardiogram showed ST segment depression in lead II, III, aVF and V2 through V5. On day 14, tall upright T-waves were observed in leads V2 through V5 despite heart failure and basal to midventricular ballooning improved on day 4, and all electrocardiographic abnormalities finally normalized after surgical removal of the pheochromocytomas. This is the first report of electrocardiographic course of inverted Takotsubo cardiomyopathy, and these findings seem as if the inverted electrocardiographic findings are contrary to those of apical ballooning.     

Malignant pheochromocytoma.

We present an interesting case of paroxysmal hypertension in a young male caused by malignant pheochromocytoma. This patient, who had history of paroxysms of abdominal pain with severe hypertension, developed osseous metastasis in the first lumbar vertebra resulting in collapse of the vertebra and it caused paraplegia. The diagnosis of pheochromocytoma was confirmed on histopathology.     

Systemic inflammatory syndrome and hepatic inflammatory cell infiltration caused by an interleukin-6 producing pheochromocytoma

Pheochromocytoma is a tumor that produces a variety of biologically active substances in addition to catecholamines. We report here a patient with a pheochromocytoma, who presented with acute inflammatory symptoms and marked abnormalities in liver function and hematological tests. A 31-year-old man, who had experienced intermittent fever, chills and weight loss during the previous several months, was referred to our hospital for further evaluation. Laboratory examination revealed anemia, leukocytosis with elevated inflammatory markers, and abnormalities in coagulation and liver function tests. Histological examination revealed a marked plasmacytosis in the bone marrow and lymphocyte infiltration into the portal area of the liver. Along with increases in serum catecholamine and urine catecholamine metabolites, his serum interleukin (IL)-6 level was increased to 300 pg/ml, compared with a normal range of 3-12 pg/ml. Left adrenalectomy was performed. The adrenal tumor was densely immunostained with antibody to IL-6. After resection of his adrenal tumor, his serum IL-6 level returned to normal (11 pg/ml) and all symptoms subsided with normalization of laboratory findings.     

Unique association of non-functioning pheochromocytoma, ganglioneuroma, adrenal cortical adenoma, hepatic and vertebral hemangiomas in a patient with a new intronic variant in the VHL gene

We analyzed the clinical, hormonal, immunohistochemical and genetic features in a 69-yr-old Caucasian woman with a very rare "composite and mixed pheochromocytoma". This was characterized by right adrenal pheochromocytoma associated with homolateral ganglioneuroma and controlateral adrenal cortical adenoma. The three tumors, incidentally discovered, proved to be non-functioning (normal secretion of catecholamines and of other neuroendocrine peptides, glucocorticoids, mineralcorticoids and androgens). Accordingly, the patient showed no sign or symptom of endocrine disease. Computed tomography (CT) and magnetic resonance (MR) demonstrated a typical adenomatous lesion on the left adrenal gland with precocious uptake of the radiotracer on radioidine (131I)-norcholesterol adrenal scintigraphy, while the controlateral gland showed hyperdensity on CT, hyperintensity on MR and no uptake at adrenal scintigraphy. In addition, CT and MR revealed a vertebral and two hepatic hemangiomas. The right adrenal gland was surgically removed and, microscopically, pheochromocytoma and ganglioneuroma areas appeared intermixed without a predominant component. The former showed strong immunoreactivity for chromogranin, synaptophysin, vascular endothelial growth factor (VEGF) and CD34, while the latter appeared positive for neuron-specific enolase (NSE) and S-100. Peripheral blood genomic DNA analysis revealed a new intronic variant (5557A > G) in the von Hippel-Lindau gene (VHL) not observed in our control population.     

Fever in pheochromocytoma.

BACKGROUND--Fever is an infrequently reported finding in patients with pheochromocytoma. Fever in patients with pheochromocytoma may be caused by the tumor, an infection or other factors, each of which will dictate different treatment strategies. METHODS--To determine the incidence, cause, and significance of fever in patients with pheochromocytoma, we reviewed the medical records of 50 hospitalizations of 48 patients. Patients were categorized by the presence or absence of fever. Body temperature elevation, duration of hospitalization in the period prior to surgery or death, age, sex, race, other conditions that could have been responsible for the febrile episode (comorbid events), location, gross and microscopic features of the tumors, and plasma and urine hormone levels were tabulated. The results were compared between the two groups of patients. RESULTS--Fever was present in 14 (28%) of 50 hospitalizations, seven patients (50%) of whom had pheochromocytoma multisystem crisis. Patients with fever and pheochromocytoma were significantly more likely to have a comorbid event, larger tumor, necrosis within the tumor, higher urinary metanephrine levels, longer duration of hospitalization prior to surgery, and to be non-white. Comorbid events included both infectious and noninfectious potential causes of fever. CONCLUSIONS--Fever is common in patients with pheochromocytoma. The causes may be multifactorial and often include an associated illness. A thorough search for coexisting disease is indicated. While fever may prolong hospitalization, it does not portend a disastrous outcome.