尿去甲基肾上腺素/甲氧基肾上腺素测定对嗜铬细胞瘤的方法学比较

目的:通过对尿儿茶酚胺代谢产物去甲肾上腺素、甲氧基肾上腺素的测定,综合分析其对嗜铬细胞瘤的早期临床诊断价值。方法:利用酶联免疫分析法和传统柱层析法,对正常人和临床诊断为嗜铬细胞瘤及肾上腺占位病变并伴有阵发性高血压患者的24h尿去甲基肾上腺素/甲氧基肾上腺素和3-甲氧基-4-羟基苦杏仁酸(VMA)进行测定。结果:与VMA相比,24h尿去甲基肾上腺素/甲氧基肾上腺素在嗜铬细胞瘤患者中的测定值要显著高于其他肾上腺占位性病变伴高血压患者和正常人群,二者方法学有显著性差异。结论:酶联免疫分析法检测24h尿去甲基肾上腺素/甲氧基肾上腺素具有灵敏度高、特异性好的特点,为临床从肾上腺占位性病变并伴有阵发性高血压患者中筛查嗜铬细胞瘤提供了一种有价值的参考方法。     

Combined adrenal myelolipoma and medullary hyperplasia

OBJECTIVE: A patient is reported with hypertension due to combined medullary adrenal hyperplasia and myelolipoma. METHODS: A 52-year-old woman with long-standing hypertension was evaluated for an incidentally discovered large tumor of the left adrenal. Left adrenalectomy was performed for a presumptive clinical diagnosis of pheochromocytoma. RESULTS: Histopathologic examination revealed a mixed tumor consisting of a large myelolipoma with infiltrating foci of adrenal medulla. CONCLUSIONS: A patient is described with hypertension, myelolipoma and adrenal medullary hyperplasia; following adrenalectomy, however, blood pressure and biochemical abnormalities normalized.     

Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.     

Acute Myocardial Infarction Attributable to Adrenergic Crises in a Patient with Pheochromocytoma and Neurofibromatosis 1

ObjectiveTo describe a rare case of acute myocardial infarction in a patient with neurofibromatosis 1 and pheochromocytoma and to review the literature on the coexistence of these 2 diseases, the causes of myocardial injury in patients with pheochromocytoma, and the utility of genetic testing and pheochromocytoma screening for those patients and their families.MethodsWe present a case report, including the detailed clinical, laboratory, and radiographic data, results of adrenal mass pathology, and results of coronary angiography. We also survey other relevant reports available in the literature.ResultsA 43-year-old woman with a history of longstanding hypertension, neurofibromatosis 1, headaches, sweating, and palpitations presented to the hospital with chest pain and shortness of breath. She was found to have an acute myocardial infarction and pulmonary edema, as well as a right adrenal mass. A pheochromocytoma was suspected, and phenoxybenzamine was added to her treatment regimen. Cardiac catheterization showed nonobstructive coronary disease. The levels of plasma catecholamine metabolites were extremely high. The patient underwent uncomplicated laparoscopic right adrenalectomy 2 weeks after this admission. Surgical pathology confirmed the diagnosis of pheochromocytoma.ConclusionAdrenergic crisis attributable to pheochromocytoma can result in acute myocardial infarction even in the absence of obstructive coronary disease. Inclusion of pheochromocytoma in the differential diagnosis of hypertension in patients with neurofibromatosis is very important and helps avoid mistakes in the management of such patients. (Endocr Pract. 2007;13:269-273)     

Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.

A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure.     

Pheochromocytoma associated with adrenocortical adenoma: case report and literature review

The case of a 60-year-old woman with pheochromocytoma and concomitant adrenocortical adenoma in the same gland is presented. She complained of episodic headache, palpitation, nausea, vomiting and sweating. Physical examination revealed that the patient has generalized obesity, wet skin and paroxysmal hypertension, but no signs of Cushing's syndrome. Elevated levels of urinary noradrenaline, adrenaline and total metanephrine were sequentially observed. In addition, urinary 17-OHCS was also slightly elevated, but plasma cortisol was normal and suppressed after oral administration of 0.5 mg of dexamethasone. Abdominal echography and CT scanning demonstrated a left adrenal tumor, which took up both 131I-meta-iodobenzylguanidine and 75Se-scintadoren in the same region. A left adrenalectomy was performed and the tumor was found to consist of two parts, pheochromocytoma (2.5 X 2.5 X 2.5 cm) and cortical adenoma (2.5 X 3 X 5 cm). A total of 23 reported cases showing evidence of hyperfunction of the adrenal cortex and the medulla were noted. So far as we know, this patient was the second case of pheochromocytoma with adrenocortical adenoma in Japan.     

Management of pheochromocytoma during pregnancy.

To reduce the high maternal and fetal mortality in pheochromocytoma of pregnancy, therapy is advocated with phenoxybenzamine and propranolol to obtain adequate alpha- and beta-adrenergic receptor blockade. In early pregnancy control of symptoms may be difficult, but the patient may be carried to term with such medical therapy. Delivery should be by cesarean section before the onset of labour, with, if possible, simultaneous removal of the tumour. Additional preoperative preparation with phenoxybenzamine and propranolol and careful intraoperative management are essential. During her third pregnancy a 29-year-old woman was found to have a pheochromocytoma of the left adrenal gland. After the medical therapy and preparation described, the infant was delivered by cesarean section and the mother''s left adrenal gland excised. Eight-year follow-up, including during a fourth pregnancy, showed no recurrence of tumour in the mother and only mild hypertension. The infant developed normally.     

Glucagon-Induced Pheochromocytoma Crisis

ObjectiveTo describe a previously asymptomatic woman who developed a glucagon-induced pheochromocytoma crisis during preparation for screening colonoscopy.MethodsWe present the patient’s clinical features, laboratory and imaging findings, and outcome and review the related literature.ResultsA 76-year-old woman received glucagon to inhibit intestinal motility before routine colonoscopy. She immediately developed severe hypertension, cardiac arrhythmia, and altered mental status. Her hospital course was complicated by encephalopathy and cardiac, respiratory, renal, and hepatic failure. Computed tomography of the abdomen showed a 6.5 × 4.8-cm mass in the left adrenal gland. Biochemical testing for pheochromocytoma revealed markedly elevated plasma catecholamines and metanephrines and urinary vanillylmandelic acid and metanephrine. She underwent a successful laparoscopic left adrenalectomy. Findings from histopathologic and immunohistochemical examination of the adrenal mass were diagnostic of pheochromocytoma.ConclusionsGlucagon administration induced catecholamine release from an occult pheochromocytoma, which caused multiorgan injury. Health care providers using glucagon must consider this rare, but life-threatening, complication. (Endocr Pract. 2011;17:e51-e54)     

Serum chromogranin-alpha immunoradiometric assay in the diagnosis of pheochromocytoma

BACKGROUND: The diagnosis of pheochromocytoma is based on laboratory tests that demonstrate an increase in urinary excretion of catecholamines or their metabolites. Chromogranin A (CgA) is a member of the granin family and is widely distributed in neuroendocrine cells and particularly in chromaffin adrenal cells. Consequently, serum CgA increases in patients affected by pheochromocytoma and other diseases of the chromaffin system. AIM: This study investigated the performance of serum CgA assay in the diagnosis of pheochromocytoma and compared serum CgA with 24-hour urinary epinephrine (E), norepinephrine (NE), vanillylmandelic acid (VMA) and metanephrines (MNs). METHODS: We enrolled 15 patients with histologically proven pheochromocytoma; 100 healthy blood donors and 148 patients with essential hypertension were enrolled as controls. Serum CgA was assayed by a specific immunoradiometric method (IRMA). Urinary tests were done with high performance liquid chromatography (HPLC). RESULTS: Circulating CgA showed a higher sensitivity (1.00), specificity (0.96) and accuracy (0.96) than all other tests. Serum levels of CgA clearly increased from blood donors and patients with essential hypertension to patients with pheochromocytoma (p<0.0001). Furthermore, a strong relationship between serum CgA and tumor mass was found (p<0.0001). In conclusion, our data suggest that the CgA assay might be used as a single test for the diagnosis of pheochromocytoma.     

Pheochromocytoma in Patients Suspected of Harboring Adrenal Meta stasis: Management and Clinical Predictors

ObjectiveTo study clinical management of patients with suspected adrenal metastasis and to assess whether there are clinical predictors of pheochromocytoma in this patient population.MethodsIn this retrospective cross-sectional study, we reviewed medical records of patients who had adrenalectomy for adrenal lesions or had adrenal biopsy performed between January 1997 and July 2007 in a large academic hospital. Patients who harbored adrenal masses that were suspected of being metastases were identified on clinical findings. Pathologic diagnosis, demographic data, clinical history, imaging studies, and laboratory test results were reviewed and compared among patients whose adrenal mass was determined to be metastasis, adenoma, or pheochromocytoma.ResultsOne-hundred sixty-three patients had adrenalectomy or had adrenal biopsy during the study period. Thirty patients (18%) had adrenal masses that were suspected of being metastases. Of the adrenal masses, 18 (60%) were metastases, 8 (27%) were benign adenomas, and 4 (13%) were pheochromocytomas. Eleven patients (37%) had biochemical testing for pheochromocytoma. Adrenal biopsy was performed without biochemical testing for pheochromocytoma in 9 patients (30%), including 2 subsequently found to have this tumor. Adrenalectomy was performed in 10 patients (33%) without biochemical testing for pheochromocytoma. Clinical parameters were similar among patients with metastasis, adenoma, or pheochromocytoma. There were no clinical predictors to suggest pheochromocytoma.ConclusionsPheochromocytoma occurs frequently in patients suspected of harboring adrenal metastasis, but this tumor is often not considered in clinical practice. The size and imaging characteristics of the adrenal mass and history of known metastasis may help clinicians in decision-making. Biochemical testing for pheochromocytoma should ideally be performed in all patients suspected of having adrenal metastasis. (Endocr Pract. 2008;14:967-972)     

A case of pheochromocytoma with renal artery stenosis and post-surgical watery diarrhea

A 35-year-old woman was admitted to our hospital with the following complaints, headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension. The technical images (abdominal CT, scintigraphic octreotide scan and renal arteriography) revealed the presence of a left adrenal pheochromocytoma and stenosis of the renal artery. Ten days following adrenalectomy, watery diarrhea appeared. The long-acting somatostatin analogue octreotide (LAR, 30 mg/month, i.m.), was started, and after 2 weeks diarrhea decreased and gradually disappeared. In conclusion, we were confronted with an unusual case of pheochromocytoma associated with renal artery stenosis and the appearance of watery diarrhea some days after surgical treatment. Treatment with octreotide brought about the remission of diarrhea in this patient.     

Late diagnosis of type 2B multiple endocrine neoplasia (MEN 2B) in a 23 year-old patient

We present a case of MEN 2B diagnosed in a 23 year-old patient on the basis of bilateral pheochromocytoma and medullary thyroid carcinoma. This young male patient also had multiple paragangliomas located along the spine, marfanoid features of body habitus and numerous mucosal neuromas of the oral cavity and intestinal ganglioneuromatosis. The patient was hospitalised several times between the ages of 11 and 14 due to heart rhythm disorders (tachycardia, multiple supraventricular beats) and pain in the precardiac area. Elevated blood pressure was not observed at that time. In 2010, the patient was admitted to hospital due to abdominal pain, nausea, vomiting and hypertension; bilateral adrenal tumours were then detected. The patient was referred to the Department of Endocrinology in Szczecin, with suspected pheochromocytoma in order to continue the diagnostic process. This resulted in the diagnosis of bilateral pheochromocytoma and medullary thyroid carcinoma. On the basis of the whole clinical picture, the diagnosis of MEN 2B was established and subsequently confirmed with genetic test results. Following the removal of adrenal tumours and thyroidectomy, the patient was referred to the Cancer Centre and Institute of Oncology in Gliwice for further treatment (X-ray therapy and further surgery due to recurrence of medullary carcinoma). This article presents a case of late MEN 2B diagnosis despite the presence of clinical symptoms suggestive of Multiple Endocrine Neoplasia observed from early childhood.     

Pheochromocytoma mimicking an acute myocardial infarction

We report a 42-year-old female who presented with retrosternal pain, dyspnoea and nausea. Electrocardiography suggested a recent anterior myocardial infarction. However, emergency coronary angiography showed normal blood flow through all the coronary arteries. Paroxysmal hypertension raised the suspicion of a pheochromocytoma. Indeed, abdominal ultrasonography and computed tomography revealed a mass in the left adrenal gland. Elevated levels of plasma and urine catecholamines supported the diagnosis of pheochromocytoma. Left adrenalectomy was performed without complications and pathological examination revealed a 5.5 cm pheochromocytoma. After surgery, all antihypertensive medication was discontinued and the blood pressure returned to normal within several days. Currently, the patient is asymptomatic, has normal catecholamine levels and the electrocardiographic signs of ischaemia have resolved entirely. This case illustrates that a rare clinical entity such as pheochromocytoma should be considered in the differential diagnosis of acute coronary syndrome. (Neth Heart J 2007; 15:248-51.)     

Cardiac Abnormalities Associated with Pheochromocytoma and other Adrenal Tumors

ObjectiveTo study the specific cardiac abnormalities associated with pheochromocytoma and to suggest a strategy for evaluating cardiac function in patients with pheochromocytoma.MethodsIn this case-control study, we reviewed pathology records of patients seen at Cedars-Sinai Medical Center between 1997 and 2007; patients with adrenal or extra-adrenal pheochromocytoma and those with nonfunctioning benign or malignant adrenal tumors were identified. Patients with functioning adrenal adenomas that secreted cortisol or aldosterone were excluded. Clinical history, imaging, pathology, biochemical test results, electrocardiographic findings, and echocardiographic findings were compared between patients with pheochromocytoma and patients with nonfunctioning adrenal tumors.ResultsThe charts of 22 patients with pheochromocytoma and 35 patients with nonfunctioning adrenal tumors were included. No perioperative mortality was observed. The average age of patients with pheochromocytoma was similar to that of control patients (51.9 ± 3.9 years vs 60.2 ± 2.5 years, respectively), as was the number of patients with known cardiovascular diseases (2 [9%] in the pheochromocytoma group vs 5 [14%] in the control group). Two patients with pheochromocytoma (9%) exhibited myocardial damage. Abnormal electrocardiographic findings were present in 16 patients with pheochromocytoma (73%) and in 17 control patients (49%) (P = .1). QTc was prolonged in patients with pheochromocytoma compared with control patients (448.3 ± 9.7 ms vs 424.7 ± 4.5 ms, respectively; P = .02) and was correlated with levels of norepinephrine and normetanephrine, but not with levels of epinephrine and metanephrine or tumor size. ST-T abnormalities were present in 11 patients with pheochromocytoma (50%) and in 8 control patients (23%) (P = .04). Echocardiographic findings were normal in most patients with pheochromocytoma; abnormal left ventricular wall motion was documented in 3 patients with long QTc.ConclusionsThe specific electrocardiographic findings in patients with pheochromocytoma are prolonged QTc and ST-T abnormalities. Performing an electrocardiogram in patients with pheochromocytoma would be prudent. Echocardiography would be useful to examine LV wall motion in patients with long QTc. Coronary artery disease should be excluded in patients with significant ST- T changes. (Endocr Pract. 2009;15:10-16)     

In vivo evidence of regulation by pituitary-adrenal axis of urinary epinephrine excretion in men

The effect of the pituitary-adrenal axis on epinephrine synthesis in the human adrenal medulla was examined by the estimation of the 24-h urinary epinephrine level after treatment with glucocorticoids in four patients with systemic lupus erythematodes (SLE), one patient with rheumatoid arthritis (RA) and one patient with adrenal pheochromocytoma. 24-h urinary catecholamines (CAs) were measured by HPLC before and after glucocorticoid treatment, dexamethasone or prednisolone was orally given for more than seven days to patients with SLE, RA or isolated ACTH deficiency and five days to a patient with adrenal pheochromocytoma. In patients with isolated ACTH deficiency, the 24-h urinary epinephrine level was significantly lower than the normal range. In patients with SLE or RA, the 24-h urinary epinephrine level was normal and it was significantly suppressed by therapeutic doses of prednisolone 30-40 mg/day. In a patient with adrenal pheochromocytoma, 24-h urinary epinephrine was extremely high and it was significantly increased after dexamethasone 0.5 mg/day. These results suggest that epinephrine synthesis in the human adrenal medulla may be dependent on the pituitary-adrenal axis. But the increase in epinephrine synthesis due to dexamethasone in a patient with pheochromocytoma may reflect the direct effect via the feeding artery to the tumor, as previously shown in an in vitro culture system.     

Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management.

There is evidence for a close interrelation between the adrenomedullary and adrenocortical tissues, and there are well-characterized models of their paracrine interaction. To contribute to the studies of systemic interactions between these tissues, we studied a 52-year-old female patient with a pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a misunderstanding, she presented to her family doctor to have an inherited kidney disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A computerized tomography of the abdomen revealed bilateral adrenal masses. Due to excess catecholamine secretion, bilateral pheochromocytomas based on multiple endocrine neoplasia syndrome were suspected. Laboratory work-up, selective adrenal venous sampling and magnetic resonance imaging studies established the diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol-producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal adrenalectomy was performed. Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right-hand adrenal gland, while the left was negative; the left-hand adrenal gland stained positive against the ACTH receptor (MC2R) while the right was negative. Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in certain inherited disorders are possible, this rare case of an adrenal pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma may further underline the wide range of complex interactions between the two endocrine systems.     

Sunitinib treatment for refractory malignant pheochromocytoma

We report the clinical response and adverse events of a female patient treated for recurrent malignant pheochromocytoma using the tyrosine kinase inhibitor sunitinib. A 41-year-old woman underwent adrenectomy and nephrectomy forpotentially malignant adrenal pheochromocytoma. Fifty-four months after surgery, abdominal computed tomography (CT) and Iodine-131 metaiodobenzylguanidine((131)I-MIBG) scintigraphy revealed multiple tumors in the liver. Two chemotherapy protocols were administered in succession (first line: cyclophosphamide/vinblastine/dacarbazine; second line: cisplatin/docetaxel/ifomide). Despite these treatments, however, the tumors continued to progress. Treatment with sunitinib was initiated, but the patient quickly developed critical hypertension caused by tumor lysis syndrome. The sunitinib dose was reduced, and a partial response, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), was observed after 6 treatment cycles. Moreover, no severe adverse events occurred during this lower-dose sunitinib treatment. Unfortunately, sunitinib treatment became unaffordable for the patient, who eventually resorted to palliative care and died 37 months later. This case study is consistent with previous reports indicating that appropriate doses of sunitinib can induce a partial antitumor response in patients with refractory pheochromocytoma.     

Pheochromocytoma manifesting with shock presents a clinical paradox: a case report

A 46-year-old man presented with shock and adult respiratory distress syndrome. Investigations revealed an adrenal mass that was diagnosed, by fine-needle aspiration biopsy, as pheochromocytoma. Because biopsy is contraindicated in patients with pheochromocytoma, this confusing presentation underscores the value of excluding this diagnosis by biochemical means before performing fine-needle aspiration of adrenal tumours.     

Nonclassic Presentation of Pheochromocytoma: Difficulties in Diagnosis and Management of the Normotensive Patient

ObjectiveTo report an unusual presentation of pheochromocytoma along with challenges in diagnosis and management.MethodsWe report a clinical case history and describe diagnostic methods and pitfalls. The preoperative medical preparation in a normotensive patient is described.ResultsA 33-year-old man fell off a ladder, resulting in C6 paraplegia. After C7-T1 laminectomy, he was transferred to a rehabilitation center where he reported lightheadedness, shortness of breath, and chest pain during therapy sessions. A left adrenal mass was incidentally discovered during the workup to rule out a pulmonary embolism. He reported no history of hypertension, and no elevated blood pressure readings had been documented. Magnetic resonance imaging of the adrenal glands showed a well-defined left adrenal mass measuring 3.9 × 3.2 × 3.3 cm, which was hyperintense on T2-weighted images. Twenty-four hour urinary catecholamine concentrations were unremarkable; urinary metanephrines were markedly elevated. During hospital admission, blood pressure was in the low to normotensive range, requiring a cautious approach to α-adrenergic blockade and surgical preparation. He underwent uneventful laparoscopic left adrenalectomy; surgical pathology was consistent with pheochromocytoma.ConclusionsThis case illustrates a nonclassic presentation of pheochromocytoma and demonstrates that urinary catecholamines alone are not sufficient for a biochemical diagnosis of large pheochromocytomas. Preoperative preparation in normotensive patients can be achieved with α-adrenergic blockade, hydration, and liberal salt intake.     

Operations on the adrenal glands

Various conditions of the adrenal gland are amenable to surgical treatment. Removal of a pheochromocytoma is almost always indicated when the tumor is diagnosed. The results of extirpation have been excellent in cases in which patients were operated upon before the onset of chronic hypertension. Removal of the "nerve cell" tumors of the adrenal is indicated if metastasis cannot be demonstrated. Hypofunction of the adrenal cortex may be partially alleviated by the repeated implantation of pellets of desoxycorticosterone acetate. Hyperfunction of the adrenal cortex causes a variety of clinical manifestations depending upon which of the numerous hormones are affected. Removal of a cortical tumor alleviates these symptoms. These tumors are malignant in more than 50 per cent of cases, and recurrence is frequent. Bilateral hyperplasia of the glands rather than a tumor may be present. In such circumstances, resection of 95 per cent of the adrenal tissue is effective in controlling the symptoms of the disease. Total bilateral excision of the adrenals is, at present, under investigation as a means of treatment for a variety of conditions.