嗜铬细胞瘤23例临床特征分析

目的通过总结嗜铬细胞瘤的临床表现,提高该病的诊治水平。方法回顾性分析23例嗜铬细胞瘤患者的临床表现、生化检查、影像学检查及辅助检查。结果 23例病例的主要临床表现为高血压伴头痛、心悸,其中阵发性高血压18例,占78.3%;持续性高血压5例,占21.7%。24小时尿儿茶酚胺均高于正常值。追踪观察手术治疗效果,疗效明显。结论对有高血压并伴有头痛、心悸的患者,应考虑嗜铬细胞瘤的诊断,以减少漏诊误诊。     

以少见表现为首发症状的9例嗜铬细胞瘤临床分析

目的：探讨以少见表现为首发症状的的嗜铬细胞瘤的临床特点.方法：回顾性分析经手术病理证实为嗜铬细胞瘤并具有特殊临床表现的9例患者的临床资料结果：2例患者术前诊断为急性冠脉综合征;2例患者术前诊断休克;1例患者术前诊断为糖尿病酮症酸中毒;4例患者术前诊断为视神经炎.所有患者均有高血压.影像学检查均发现肾上腺占位病变,均经手术病理证实为肾上腺嗜铬细胞瘤,术后症状好转.结论：嗜铬细胞瘤表现多样化,高血压是重要的诊断线索,实验室及影像学检查对明确诊断有重要意义.     

肾上腺外嗜铬细胞瘤11例临床分析

回顾性分析新疆维吾尔自治区人民医院1998年至2008年11例经手术后病理证实为肾上腺外嗜铬细胞瘤的临床表现、定性和定位检查资料.肾上腺外嗜铬细胞瘤的定性诊断与肾上腺内嗜铬细胞瘤者相同,但定位诊断常较困难,即使131I-MIBG阳性率比较低,结合病史、临床特点以及B超、CT、MRI等检查可提高诊断的阳性率.一旦确诊,手术治疗是最佳选择.     

再论鉴别高血压病因的重要意义

继发性高血压占高血压人群5％(3．7％-11％),其病因至少有50多种,以肾实质性高血压最为多见,其次为肾血管性高血压、原醛、嗜铬细胞瘤、睡眠呼吸暂停综合征,妊娠期高血压疾患等,通过病史、临床表现、实验室与影像学检查及肾脏活检明确病因诊断,具有介入或手术指征者,可以获得痊愈。     

嗜铬细胞瘤的诊治策略

嗜铬细胞瘤是一种少见的疾病,其在高血压人群中的患病率为0.5%～1%,其所致恶性高血压是导致心力衰竭、心肌梗死、脑卒中和肾功能受损的重要危险因素,因此对嗜铬细胞瘤的早期诊断、早期治疗显得尤为重要.现就嗜铬细胞瘤的临床特征、生化诊断、定位诊断、处理、基因筛查等进行探讨.     

恶性嗜铬组织肿瘤的诊断进展

嗜铬组织肿瘤主要包括嗜铬细胞瘤及副神经节瘤,其中10%的嗜铬细胞瘤为恶性,而副神经节瘤的恶性发生率更高.目前临床表现、生化指标及组织病理学结果并不能完全区分肿瘤的良恶性.一些影像学方法对于肿瘤的定性、定位诊断有特殊的意义.近年来根据基因表达谱来鉴别嗜铬组织肿瘤的良、恶性已成为日后研究的方向.     

肾上腺外嗜铬细胞瘤25例临床分析

目的 分析肾上腺外嗜铬细胞瘤的发病情况，病理特征及诊断方法，探讨治疗措施。方法 通过对81例经手术与病理证实的嗜铬细胞瘤进行回顾性分析。结果 81例嗜铬细胞瘤患者中，经手术与病理证实的肾上腺外嗜铬细胞瘤25例，占同期收治嗜铬细胞瘤的30．9％。病人的临床表现除特殊部位肿瘤外与肾上腺髓质嗜铬细胞瘤相似。结论 肾上腺外嗜铬细胞瘤临床表现与生化诊断与肾上腺髓质嗜铬细胞瘤相似，其恶性者较肾上腺髓质嗜铬细胞瘤明显增多，定位诊断以^131I-MIBG为特异，治疗以手术最佳。     

肝嗜铬细胞瘤1例报告

正嗜铬细胞瘤是一种起源于肾上腺嗜铬细胞的神经内分泌肿瘤,它可以持续或间断分泌儿茶酚胺,包括去甲肾上腺素、多巴胺及肾上腺素。肾上腺外来源的嗜铬细胞瘤称为转移性嗜铬细胞瘤。嗜铬细胞瘤典型的临床表现有血压异常波动、心悸、头疼等,严重者可导致高血压危象,危及生命。本文报道了1例位于肝右后叶的嗜铬细胞瘤的青年患者,并讨论了临床表现、影像学表现、组织学病理和治疗方法。1病例资料     

以特殊临床表现为首发症状的10例嗜铬细胞瘤临床诊治分析

目的探讨特殊临床表现的嗜铬细胞瘤的诊治。方法回顾性分析西安交通大学医学院第一附属医院1995—2005年10例经手术后病理证实为嗜铬细胞瘤的临床特点。结果10例患者术前24h尿3-甲氧基-4-羟苦杏仁酸(VMA)87.6～175.5μmol、24h尿儿茶酚胺(CA)611.1～5421.0nmol、24h尿肾上腺素(E)168.2～2402.0nmol和24h尿去甲肾上腺素(NE)422.9～3019.0nmol,均明显高于正常,CT或B超检查均发现肾上腺占位病变。2例术前表现为急性冠脉综合征的患者,术后随访无心绞痛发作;4例有高血糖诊断为糖尿病的患者,术后血糖逐渐恢复正常;另外,4例以腹痛为首发症状的患者,术后症状未再反复。结论临床表现不典型的嗜铬细胞瘤患者,生化检查及影像学检查对明确诊断很有意义。     

嗜铬细胞瘤28例诊断分析

目的总结嗜铬细胞瘤的临床特点,探讨各种检查方法对嗜铬细胞瘤诊断的价值。方法对北京协和医院2004-01~2005-03的28例经手术和病理证实的嗜铬细胞瘤进行回顾分析。结果定性检查结果:24h尿儿茶酚胺(尿CA)检测结果为多巴胺升高占7例,去甲肾上腺素升高占24例,肾上腺素升高占15例,三者均正常2例。定位检查:各种检查阳性率分别为B超77%(17/22),CT96%(26/27),MIBG显像78%(22/28),奥曲肽显像73%(11/15)。结论尿儿茶酚胺对嗜铬细胞瘤的定性诊断有较高的诊断价值,而CT在定位方面有较高的敏感性,MIBG和奥曲肽显像可作为嗜铬细胞瘤定性和定位的可靠依据。     

58例儿茶酚胺增多症代谢状况分析

目的：分析儿茶酚胺增多症的代谢状况,提高其临床诊治水平和认识。方法：收集分析1998年1月至2008年4月新疆维吾尔自治区人民医院收治的58例儿茶酚胺增多症的临床资料。结果：58例儿茶酚胺增多症患者中肾上腺嗜铬细胞瘤46例（79．3％）,肾上腺外嗜铬细胞瘤11例（19．0％）,肾上腺增生1例（1．7％）;临床有典型“三联征”8例（13．8％）,表现为“三联征”症状之一的有48例（82．8％）,血压升高的48例（82．8％）,伴有糖代谢异常的共19例（32．8％）,高脂血症16例（27．6％）,低钾血症7例（12．1％）;CT检查阳性58例（100％）。结论：儿茶酚胺增多症可表现为血糖、血脂、钾离子代谢紊乱,这对于其诊断具有一定价值。     

Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma

In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.     

Malignant pheochromocytoma: predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center

Metastases appear in approximately 10% of patients with pheochromocytoma. There is no predictive marker of malignancy. The aim is to describe clinical course of patients with malignant pheochromocytoma and to identify predictive features of malignancy. The method involves retrospective analysis of patients files diagnosed with malignant pheochromocytoma at our institution between January 1, 1980 and December 31, 2008. We identified 16 patients with malignant pheochromocytoma. There were more men than women (10/6). Mean age of patients at time of diagnosis was 37.75-year-old. Time of occurrence of metastases ranged from 0 to 22 years after first diagnosis of pheochromocytoma. The mean size of the primary tumor was 12.1 cm. High levels of chromogranin A at the time of diagnosis were associated with the presence of metastases. The pheochromocytoma of the adrenal gland scoring scale (PASS) histological evaluation in adrenal primary tumors was above four in all cases but one. All patients had initial surgery, followed in most cases by palliative therapy: chemotherapy (streptozocin, cyclophosphamide-vincristine-dacarbazine, thalidomide, imatinib, everolimus) or (131)I-MIBG; only the latter had replicable encouraging response evaluation criteria in solid tumor response rates. We observed a 10-year survival rate of 50% after initial diagnosis of pheochromocytoma, and 25% after diagnosis of metastasis. Metastasis can occur very late after the initial diagnosis of pheochromocytoma. High chromogranin A levels may be associated with the presence of metastases and poor prognosis. Histological adrenal PASS higher than 4 appears to be suggestive of malignancy. The best therapeutic approach remains to be established.     

Reversible cerebral ischemia in patients with pheochromocytoma

Cerebral ischemia and symptoms of stroke can occur as a rare manifestation in patients with pheochromocytoma. We describe a 45-year-old woman who was admitted because of a right-sided hemiparesis due to an ischemic lesion in the left hypothalamus. The clinical diagnosis of a pheochromocytoma was proven by highly elevated urinary catecholamines and confirmed histologically after operation. The successful removal of the tumor led to the almost complete recovery of the neurological deficiencies. It is of vital importance to know this atypical presentation of pheochromocytoma. The diagnosis of pheochromocytoma should be suspected in patients with focal cerebral symptoms, particularly in the presence of intermittent hypertension or other paroxysmal symptoms suggestive of pheochromocytoma.     

Epinephrine producing pheochromocytoma. Is the secretory pattern decisive for the clinical manifestation?

Adrenal incidentalomas are becoming a major clinical problem, due to increasingly frequent radiological examinations. We present two cases of patients referred to our department with a finding of an unsuspected adrenal mass. Both of them were normotensive and without symptomatology typical for pheochromocytoma. In one patient we found 20-times higher levels of epinephrine and 3-times higher levels of dopamine in 24-h urine, in the second patient there were 8-times higher levels of epinephrine alone. Norepinephrine in urine, as well as values of all adrenal cortical hormones were normal. The diagnosis of pheochromocytoma was confirmed in both cases by a 123I-metaiodobenzylguanidine (MIBG) scintigraphy. The patients underwent adrenalectomy, which was performed without complications. We conclude that levels of single catecholamines excreted are decisive for the clinical presentation of pheochromocytoma. Epinephrine producing pheochromocytoma is more often oligo- or asymptomatic. We stress the importance of a complete hormonal screening in every case of adrenal incidentaloma, with measuring levels of catecholamines and/or metanephrines.     

Endomyocardial biopsy in a patient with hemorrhagic pheochromocytoma presenting as inverted Takotsubo cardiomyopathy

A 29-year-old female patient presented with shock and dyspnea due to heart failure and pulmonary edema. Echocardiography indicated excessive contraction limited to the left ventricular apex and akinesis of the basal and middle ventricle, which were confirmed by emergency left ventriculography. The finding was diagnostic of inverted Takotsubo cardiomyopathy. An abdominal computed tomography scan showed a tumor in the left adrenal gland with a central low-density area, and the plasma and urinary catecholamines were strikingly elevated. Taken together, these findings suggested the presence of a hemorrhagic pheochromocytoma. A myocardial biopsy in the very acute stage on the day of admission revealed neutrophilic infiltration and contraction-band necrosis, which was indistinguishable from the previously reported pathology in the acute phase of idiopathic Takotsubo cardiomyopathy without pheochromocytoma. The diagnosis of pheochromocytoma in this case was confirmed 7 weeks later by surgical removal of the left adrenal gland with massive hemorrhage at the center of the pheochromocytoma. The marked similarity of the endomyocardial pathology between this case and cases with idiopathic Takotsubo cardiomyopathy strongly points to catecholamine excess as a common causality for Takotsubo cardiomyopathy with or without pheochromocytoma.     

Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results

Measurements of plasma normetanephrine and metanephrine provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44-45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results.     

Free plasma metanephrines as a screening test for pheochromocytoma in low-risk patients

OBJECTIVES: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated. METHODS: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma. RESULTS: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%. CONCLUSION: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.     

Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma

Chromogranin A, co-stored and co-released with catecholamines from adrenal medullary and sympathetic neuronal vesicles, is elevated in the plasma of patients with pheochromocytoma. The usefulness of the hormone in the differential diagnosis of hypertension is examined. An elevated level of chromogranin A had comparable diagnostic sensitivity (83%, 24/29) to, but greater diagnostic specificity (96%, 86/90) than the level of plasma catecholamines when subjects with pheochromocytoma (n = 29) were evaluated in comparison to several reference groups, including normotensive controls (n = 49), subjects with essential hypertension (n = 28), subjects with renovascular hypertension (n = 5), and subjects with primary aldosteronism (n = 3). Subjects with signs or symptoms suggesting pheochromocytoma, but in whom the diagnosis was ultimately ruled out (n = 5) had normal plasma levels of chromogranin A. A modest rise in chromogranin A in those with essential hypertension, and correlation of chromogranin A with diastolic blood pressure in normotensive patients and patients with essential hypertension did not impair the diagnostic usefulness of chromogranin A for pheochromocytoma. Renal failure was associated with an elevated plasma chromogranin A independently of blood pressure. Plasma chromogranin A correlated with tumor mass, tumor chromogranin A content, tumor norepinephrine content, and urinary vanillylmandelic acid excretion; it did not correlate with plasma or urinary catecholamines, nor with blood pressure in patients with pheochromocytoma. Plasma chromogranin A levels did not differ in subjects with pheochromocytoma when stratified by age, sex, tumor location, or tumor pathology. Several drugs used in the diagnosis or treatment of pheochromocytoma (clonidine, metoprolol, phentolamine, and tyramine) had little effect on plasma chromogranin A concentration. Within the pheochromocytoma, chromogranin A was localized along with catecholamines to the soluble core of chromaffin granules, where it accounted for 18 +/- 5% of vesicle soluble protein. We conclude that 1) chromogranin A emerges along with catecholamines from pheochromocytoma chromaffin granules; 2) plasma chromogranin A is a sensitive and specific diagnostic tool in evaluation of actual or suspected pheochromocytoma; 3) plasma chromogranin A predicts pheochromocytoma tumor size and overall catecholamine production; and 4) drugs commonly employed in the diagnosis or treatment of pheochromocytoma have little effect on plasma chromogranin A level, preserving the usefulness of chromogranin A in evaluating pheochromocytoma. Thus, measurement of chromogranin A provides a useful adjunct to the diagnosis of pheochromocytoma.