Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines

BACKGROUND: Measurements of plasma free metanephrines (normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. METHODS: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. RESULTS: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P <0.001), whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41 and 0.44). All tumors in which increases in plasma metanephrine were >15% of the combined increases of normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to normetanephrine accurately predicted adrenal locations. CONCLUSIONS: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures.     

Is supine rest necessary before blood sampling for plasma metanephrines?

BACKGROUND: The impact of blood sampling in sitting vs supine positions on measurements of plasma metanephrines for diagnosis of pheochromocytoma is unknown. METHODS: We compared plasma concentrations of free metanephrines in samples from patients with primary hypertension obtained after supine rest with those obtained in the sitting position without preceding rest. We also assessed the effects on diagnostic test performance retrospectively in patients with and without pheochromocytoma, and we calculated cost-effectiveness for pheochromocytoma testing. RESULTS: Upper reference limits of plasma free metanephrines were higher in samples obtained from seated patients without preceding rest than from supine patients with preceding rest. Application of these higher upper reference limits to samples from supine patients with pheochromocytoma decreased the diagnostic sensitivity from 99% to 96%. In patients without pheochromocytoma, adjusting the plasma concentration for the effects of sitting while preserving the 99% sensitivity by use of the supine upper reference limits increased the number of false-positive test results from 9% to 25%. CONCLUSIONS: To preserve high diagnostic sensitivity we recommend the use of upper reference limits determined from blood samples collected in the supine position. Under these conditions, negative test results for blood samples obtained with patients sitting are as effective for ruling out pheochromocytoma as negative results from samples obtained after supine rest. Repeat testing with samples obtained in the supine position offers a cost-effective approach for dealing with the increased numbers of false-positive results expected after initial sampling in the sitting position.     

Diagnosis of pheochromocytoma

The purpose of this article is to give an overview on recent advances in the diagnosis, localization by imaging and treatment of pheochromocytoma. Pheochromocytoma is a mostly benign tumor (malignancy rate 10-15%) which arises from chromaffin cells with excessive catecholamine production and secretion. Most tumors are localized in the adrenals but 15-18% of the lesions are found extraadrenally (paragangliomas). Pheochromocytoma is a rare form of secondary hypertension; it can also be found as a feature of familial disease (e.g. von Hippel-Lindau disease, MEN type II) due to genetic mutations of several genes that have been identified recently. In familial pheochromocytoma molecular genetic analysis has improved the diagnostic modalities. In such patients the tumor can occur bilaterally and patients often remain normotensive until the tumor produces sufficient catecholamines to have hemodynamic effects. The extreme importance of recognizing this tumor is evident from the fact that it can be successfully removed in about 90% of the cases, whereas if unrecognized the tumor poses great risk of death or devastating complications. Diagnostic screening includes measurement of catecholamines and their metabolites (metanephrines) in plasma and/or urine. Furthermore, pharmacological testing (e.g. clonidine suppression test) may be indicated in patients with moderately elevated catecholamines or when the diagnosis is still uncertain. Several imaging techniques are applied to localize the tumor. Abdominal CT scan is still considered the "gold standard" since about 98% of the tumors lie infradiaphragmatically. Magnetic resonance imaging (MRI) and MIBG-scanning are other useful methods. Recently, positron emission tomography (PET) based techniques have also been developed. After the diagnosis is made tumor removal following pharmacological pretreatment is the decisive therapeutic measure.     

Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma

BACKGROUND: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. METHODS: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration-time curve over 120 min. RESULTS: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 +/- 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. CONCLUSIONS: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.     

酶联免疫法检测间甲肾上腺素类物质在嗜铬细胞瘤诊断中的应用

目的：探讨间甲肾上腺素类物质（MNs）用酶联免疫法（ELISA）检测在嗜铬细胞瘤诊断中的价值。方法检测疑似嗜铬细胞瘤患者63例及健康人30例（作对照）血MNs,包括甲氧基肾上腺素（NMN）、甲氧基去甲肾上腺素（MN）水平,嗜铬细胞瘤以术后病理诊断为标准。结果63例临床上疑为嗜铬细胞瘤患者中32例经组织学诊断为嗜铬细胞瘤,其中ELISA检测NMN的特异性95%、敏感性91%,MN特异性92%、敏感性72%,NMN和MN二者合并检测特异性97%、敏感性93%。结论血浆游离MNs是诊断嗜铬细胞瘤的有效生化指标,ELISA法作为一种便捷可靠的检测方法,在诊断嗜铬细胞瘤中有着较高的特异性和敏感性。     

血浆游离甲氧基肾上腺素水平在诊断嗜铬细胞瘤中的价值

目的 探讨酶联免疫分析法(EIA)检测血浆游离甲氧基肾上腺素[3-甲氧基肾上腺素(MN)和3-甲氧基去甲肾上腺素(NM)]诊断嗜铬细胞瘤的价值.方法 病理确诊的30例嗜铬细胞瘤患者和51例高血压患者,用EIA检测血浆MN和NM,结合[3]I-间碘苄胍(MIBG)全身扫描结果进行分析比较.结果 嗜铬细胞瘤组30例患者全身扫描均呈阳性;高血压组中有15例接受全身扫描,结果均呈阴性;嗜铬细胞瘤组MN浓度的中位数为59.3 ng/L,高于高血压组(中位数为33.7 ng/L,Z=-2.440,P<0.05);2组NM浓度的中位数分别为652.0 ng/L和36.3 ng/L,显著高于高血压组(Z=-6.699,P<0.001);2项联合检测(任一或全部阳性)的敏感度、特异度和准确性分别为96.7%(29/30),86.3%(44/51)和90.1%(73/81),联合检测的准确性与全身扫描结果比较,差异无统计学意义(100.0%,P>0.05).结论 EIA法检测血浆游离甲氧基肾上腺素对嗜铬细胞瘤具有较高的诊断效能,有可能替代高压液相层析法而成为该病诊断的首选方法.     

Urinary metanephrine radioimmunoassay: comparison with the colorimetric assay

A radioimmunoassay involving an 125I ligand has been developed and applied to the measurement of urinary metanephrine. To validate the clinical usefulness of this assay, we compared measurement of metanephrine by radioimmunoassay and of total urinary metanephrines by the Pisano colorimetric method. The radioimmunoassay is specific for metanephrine, whereas the colorimetric method measures both metanephrine and normetanephrine. We used both methods to determine urinary metanephrine or total metanephrines in subjects with essential hypertension, pheochromocytoma, the syndrome of multiple endocrine adenomatosis type 2, and normotensive volunteers. The mean and upper limit of normal (3 SD) for metanephrine by radioimmunoassay in our normotensive volunteers was 94.2 microgram/24 h and 229 microgram/24 h, respectively, which compares well with reported values of 87.6 microgram/24 h and 319 microgram/24 h by non-radioimmunoassay methods. Both radioimmunoassay and colorimetry accurately identified five patients with known pheochromocytoma. Good correlation (r = 0.993) was demonstrated between the two assays in a comparison of patients with essential hypertension and pheochromocytoma. We conclude that the radioimmunoassay is at least equivalent to the colorimetric methods in distinguishing pathological and normal catecholamine secretion, and is faster, more precise, and 1000-fold more sensitive.     

A five-year report on experience in the detection of pheochromocytoma

Objective: The purpose of the study is to identify biochemical tests that are good predictors for the diagnosis of pheochromocytoma in patients at hypertension.

Setting: Review of data from of 3826 patients studied over a 5-year period, between 1994 and 1998, at the University Hospital “Virgen de la Arrixaca” Murcia, Spain.

Design and Methods: A retrospective study for the diagnosis of pheochromocytoma of 24-h urinary free catecholamines (norepinephrine, epinephrine, and dopamine) measured by high-performance liquid chromatography (HPLC)-electrochemical detector (ECD), total metanephrines (MNt), and vanillylmandelic acid measured by spectrophotometric methods.

Results: During this period, 57 patients were found to have pheochromocytoma, being 47 sporadic, 9 with multiple endocrine neoplasia type 2A, and 1 with neurofibromatosis. In all patients multiple endocrine neoplasia type 2A the tumor were bilateral but only in four of the sporadic tumor group (p < 0.0001, Fisher’s exact test). MNt was determined to be the best discriminator of hypertension and pheochromocytoma. It scored a sensitivity of 94.7% (95% confidence interval, 88.3–99.9%), a specificity of 95.3% (89.5–99.9%), and thus had the best negative predictive value of 99.9% (99.8–99.9%), and this biochemical test also had the best positive predictive value of 23.3% (10.8–59.9%). When combining both MNt and norephinephrine, the positive predictive value to increases to 85.6% (65.3–95.6%).

Conclusion: Urinary 24-h MNt excretion level is the best single biochemical test for screening and, in combination with norephinephrine, is diagnostic of the presence of pheochromocytoma.     

Determination of plasma methoxyamines.

The determination of plasma methoxyamines is the most informative parameter for the diagnosis of pheochromocytoma. Very good sensitivity and specificity are necessary for this. The measurement of deconjugated (free plus sulfate-conjugated) metanephrines is more useful. Concentrations are 10-fold higher than free metanephrine concentrations. The methodology generally uses a column purification and high performance liquid chromatography with electrochemical detection. We have tested six commercial columns used for the purification step. We chose a rapid and reliable method with a mixture of strong cation-exchange and strong anion-exchange groups bonded onto a silica column. This protocol has been validated with samples of plasma from normal subjects, healthy elderly people, renal failure patients and patients with pheochromocytoma.     

Performance of plasma free metanephrines measured by liquid chromatography–tandem mass spectrometry in the diagnosis of pheochromocytoma

BackgroundPlasma free metanephrines have proved a highly sensitive biochemical test for the diagnosis of pheochromocytoma. We have developed and validated a simple, LC–MS/MS method to determine plasma metanephrines and compared the diagnostic efficacy of the method with an enzyme immunoassay procedure in 151 patients, 38 with histologically confirmed pheochromocytoma.MethodsOff-line solid phase extraction in a 96-well plate format was used to isolate metanephrines from 100-μL of plasma, followed by rapid separation with hydrophilic interaction chromatography. Mass spectrometry detection was performed in multiple-reaction monitoring mode using a tandem quadrupole mass spectrometer with positive electrospray ionization.ResultsDetection limits were < 0.1 nmol/l with method linearity up to 23.0 nmol/L for normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT). Method comparison with an automated LC–MS/MS yielded Deming regression slopes of r = 0.94 for NMN, r = 0.98 for MN and r = 0.94 for 3-MT. Method comparison with enzyme immunoassay revealed regression slope of r = 1.28 (NMN) and 1.25 (MN) with values approximately 25% lower than LC–MS/MS. Plasma metanephrines by LC–MS/MS identified all 38 patients with phaeochromocytoma compared with 36 cases by immunoassay.ConclusionsPlasma metanephrines measured by LC–MS/MS are a reliable and sensitive test for the biochemical detection of pheochromocytoma.     

Freedom from drug interference in new immunoassays for urinary catecholamines and metanephrines

BACKGROUND: Determination of urinary free catecholamine and total (i. e., free plus conjugated) metanephrine excretion is considered the most clinically sensitive biochemical test for pheochromocytoma. In this study, we evaluated new immunoassay methods for the measurement of these analytes for potential drug-based interference. METHODS: Urine samples collected from patients on a variety of medications were grouped by specific drug type. The significance of any difference in the free catecholamine or total metanephrine concentrations in the different groups was assessed by one-way ANOVA. A group of patients receiving no medication was included as a control (no analytical interference). Additionally, analytical accuracy, detection limit, and precision were determined. RESULTS: No significant differences were found in the concentrations of free catecholamines or total metanephrines in urine from patients taking the medications investigated and the control group: P = 0.649 (fE), 0.221 (fNE), 0.149 (tM), and 0.170 (tNM). For free catecholamines, intraassay CVs were 4.6-18%; interassay CVs were 10-25%. For total metanephrines, intraassay CVs were 9.6-27%; interassay CVs were 5. 8-22%. Detection limits were 0.009 and 0.027 micromol/L for fE and fNE and 0.119 and 0.346 micromol/L for tM and tNM, respectively. CONCLUSIONS: None of the drugs examined in this study interfered in the measurement of free catecholamines or total metanephrines by these immunoassays. The technique is easier to use, requires less equipment, and is more accessible than HPLC. In combination, these assays are suitable as initial screening tests for pheochromocytoma.     

Multiple paragangliomas in a pregnant patient with a succinate dehydrogenase B mutation

In this case report, we document the clinical course, laboratory findings, and imaging findings of a 21-year-old pregnant woman with multiple paragangliomas due to a succinate dehydrogenase B (SDHB) mutation. We also review the literature on previously reported cases. The patient presented with nausea, palpitations, angina, and amenorrhea. Her blood pressure was 170/100 mm Hg and her beta-human chorionic gonadotropin was positive. Her blood pressure remained high despite phenoxybenzamine titration. A 24-hour urine analysis revealed elevated plasma metanephrines. Imaging was initially deferred due to early gestational age. After the patient terminated the pregnancy, magnetic resonance imaging revealed a left suprarenal mass, a mass at the aortic bifurcation, and a left periaortic mass. Her blood pressure was controlled on phenoxybenzamine and labetalol. The masses were excised. Pathology revealed paragangliomas. Genetic testing revealed mutation in the SDHB gene. One month later, her blood pressure was 122/86 mm Hg off of medication. Paraganglioma/pheochromocytoma should be suspected when hypertension occurs early in pregnancy. Genetic testing is important, as this may impact future offspring.     

Fulminant adrenergic myocarditis complicated by pulmonary edema,cardiogenic shock and cardiac arrest

Adrenergic myocarditis is an uncommon presentation of pheochromocytoma and extremely rare cause of de novo acute heart failure (AHF). We present a case of a 31-year-old Caucasian woman with a history of hypertension and recurrent occipital headaches who was admitted to the emergency department due to severe de novo AHF presenting as pulmonary edema and cardiogenic shock. During the hospital admission the patient experienced asystolic cardiac arrest and was successfully resuscitated, intubated, and mechanically ventilated. Bedside transthoracic echocardiography revealed severe diffuse left ventricular hypokinesis with ejection fraction (LVEF) of 10%. Coronary angiography disclosed normal epicardial coronary arteries. The diagnosis of fulminant myocarditis was based on clinical, laboratory and imaging findings including cardiac magnetic resonance imaging (cMRI) Lake Louise criteria. STIR-cMRI sequences revealed myocardial edema in the lateral, inferior and posterior walls of the left ventricle, whereas T1-weighted early contrast-enhanced sequences showed myocardial hyperemia and capillary leak. An ultrasound and computed tomographic scan of the abdomen disclosed a solid, heterogeneous mass (3.6 × 3.2 × 2.8-cm) in the right suprarenal area. Urinary and plasma catecholamines and metanephrines were markedly elevated. A pheochromocytoma was suspected and laparoscopic resection of the tumor was performed after pharmacological preparation with phenoxybenzamine. The histopathological findings were consistent with pheochromocytoma. Follow-up cMRI showed complete reversal of myocardial edema and hyperemia. At 12-month follow-up, the patient has remained asymptomatic and normotensive with no recurrence of cardiovascular symptoms.     

Increased catecholamine excretion after labetalol therapy: a spurious effect of drug metabolites

Patients with essential hypertension were treated for four weeks with the alpha- and beta-adreno-receptor blocking agent labetalol. Urinary excretion of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid was measured with various methods before and during treatment. An unidentified substance interfering with the fluorimetric method for catecholamines and the photometric assay for metanephrines caused falsely high values of those substances. Using appropriate methodology no changes of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid excretion were found after labetalol therapy. Our findings are important in preventing errors in the diagnosis of pheochromocytoma as well as in the evaluation of the effects of labetalol on the sympathetic nervous system in man.     

Stability of urinary fractionated metanephrines and catecholamines during collection, shipment, and storage of samples

BACKGROUND: Measurements of 24-h fractionated urinary metanephrines and catecholamines are used for the diagnosis of pheochromocytoma, but adequate information is needed regarding collection, storage, and shipment conditions. METHODS: Spot urine samples were collected from 8 healthy volunteers. Aliquots were immediately frozen at -20 degrees C, or acidified to pH 4 and then frozen either directly or after 24 h at room temperature. The remaining urine was left at room temperature for 24 h and then split into one portion that was acidified and one portion that was not. Aliquots were either frozen or allowed to stand at room temperature for an additional 24, 48, 72, 96, and 168 h before freezing. We also tested the efficacy of adding Na(2)EDTA and Na(2)S(2)O(5), as an alternative to acidification for preservation of the catecholamines. RESULTS: No clinically relevant degradation (<5%) was observed for the fractionated metanephrines under any of the storage conditions. In contrast, in approximately 50% of the untreated samples catecholamines were partially degraded during the first 24 h at room temperature. Immediate acidification, however, prevented degradation, whereas acidification after 24 h prevented further decay. Addition of Na(2)EDTA and Na(2)S(2)O(5) fully prevented degradation of catecholamines during the first 24 h in 4 of 5 cases. In the remaining case, degradation did not exceed 10%. CONCLUSION: Preservation of samples for measurements of urinary fractionated metanephrines is not necessary if samples are assayed or frozen within 1 week, which is an important advantage if transport of samples is necessary. In contrast, urinary catecholamines require preservation measures during collection.     

心脏嗜铬细胞瘤临床病理分析

目的 探讨心脏嗜铬细胞瘤的临床病理特点。方法 观察和分析3例心脏嗜铬细胞瘤的病理组织学形态特征及免疫组化标记，并结合文献总结心脏嗜铬细胞瘤的临床和病理学特点。结果 患者均以血压增高、多汗、头痛、心悸就诊，24h尿儿茶酚胺测定值明显增高，早期影像学检查未能发现占位，生长受体抑素显象阳性。光镜下细胞大小差别大，核异型性明显，偶见核分裂；其中2例有周围组织浸润，1例可见片状坏死。免疫组化l（i．67、嗜铬粒素A和S-100均有明确表达，其中2例Ki-67指数〉3％。结论 心脏嗜铬细胞瘤极罕见，部位特殊使得诊断复杂，病理形态与肾上腺原发嗜铬细胞瘤类似。Ki-67指数〉3％，组织伴有坏死，加上术后尿儿茶酚胺仍不正常，提示恶性潜能。     

肾上腺外嗜铬细胞瘤的诊断与治疗体会(附4例报告)

目的 探讨肾上腺外嗜铬细胞瘤的诊断和手术治疗体会。方法 回顾性分析4例不同部位的肾上腺外嗜铬细胞瘤的诊断和治疗经过。结果 本组均以高血压为主要临床表现。肿瘤位于腹主动脉旁1例，左上纵隔内1例，左侧腰椎旁1例，膀胱内及两侧髂内血管旁多发肿瘤1例，其中恶性嗜铬细胞瘤1例。均手术切除肿瘤，无手术并发症。结论 肾上腺外嗜铬细胞瘤临床表现和生化诊断与肾上腺嗜铬细胞瘤相似，但定位诊断较困难。定位诊断主要依靠超声、CT扫描及磁共振检查，配合同位素间碘变甲胍(^131I-MIGB)和血管造影。外科手术是最好的治疗手段。     

Amoxicillin-associated interference in an HPLC–EC assay for urinary fractionated metanephrines: Potential pitfall in pheochromocytoma biochemical diagnosis

Objective

Measurement of urinary fractionated metanephrines represents a first-line test for the biochemical diagnosis of pheochromocytoma. The high performance liquid chromatography coupled to electrochemical detection (HPLC–EC) assays used in the routine clinical laboratory can be subjected to analytical interferences by the presence of drugs or their metabolites. In this paper we describe the interference on urinary normetanephrine (uNMN) caused by amoxicillin.

Design and methods

Two pediatric patients suspected of pheochromocytoma had very high uNMN levels (2543 and 4227 μg/g Cr respectively; upper reference value: 339 μg/g Cr). Amoxicillin interference was assessed by comparison for co-elution with uNMN and by LC–MS/MS analysis.

Results

After amoxicillin interference was suspected and the therapy was stopped uNMN levels returned to normal (149 and 214 μg/g Cr respectively). Chromatograms obtained by HPLC–EC clearly showed that amoxicillin co-elutes with uNMN. Patients' uNMN levels measured by LC–MS/MS were in the normal range.

Conclusion

Amoxicillin is responsible for analytical interference on HPLC–EC assay for uNMN. This finding can be of help in distinguishing true-positive from false-positive results in the course of a biochemical diagnosis for pheochromocytoma.     

Malignant pheochromocytoma presenting as incapacitating bony pain

Among adrenal incidentalomas, pheochromocytomas are rare. Malignant pheochromocytoma is even less common, and it typically presents with classic hormonal symptoms, such as palpitations, labile blood pressures, and headaches. Bony metastasis usually occurs late in disease, but we report an unusual case of incapacitating bony pain as the initial presentation of malignant pheochromocytoma. Our patient is a 70-year-old woman with neurofibromatosis type 1 and a history of primary hyperparathyroidism, who tested negative for the ret mutation. She came to medical attention with chest pain and palpitations and was incidentally found to have an adrenal mass. Serum and urine testing was consistent with pheochromocytoma. Her blood pressure was easily controlled as she awaited elective adrenalectomy; however, she quickly developed severe, diffuse bony pain. She represented with hypercalcemia, spontaneous fractures, and incapacitating pain that required such high doses of pain medications that she had to be intubated. Further imaging and bone marrow biopsy confirmed metastatic neuroendocrine tumor. She received one round of chemotherapy with no change in her bony pain, which was her primary complaint. Unfortunately, her treatment options were limited by the heavy sedation required for comfort, and in the end, it was her bony pain rather than hormonal symptoms that made her disease untreatable.     

Pheochromocytoma: a clinical review.

Few disorders of endocrine function are so sudden and dramatic in their presentation as those caused by a pheochromocytoma. This chromaffin cell tumor arises within the adrenal medulla or within the sympathetic nervous system and causes wide fluctuations in blood pressure, tachydysrhythmias, and manifestations of intense anxiety. The patient experiences explosive paroxysms of catecholamine overload. The diagnoses of accelerated hypertension or panic disorder often are prematurely adopted. The condition kills, with deaths primarily attributed to irreversible cardiovascular and end-organ damage caused by profound hypertension. For those with a pheochromocytoma, the disorder caused by the tumor is a terrifying constellation of symptoms. Although pheochromocytoma is rare, it must be considered in the treatment of any patient with sudden, extreme hypertension and accompanying hypermetabolism. A cure is possible, but only with early diagnosis and treatment.