A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.     

Performance of Plasma Fractionated Free Metanephrines by Enzyme Immunoassay In the Diagnosis Of Pheochromocytoma and Paraganglioma in Children

ObjectiveTo establish pediatric reference ranges for plasma fractionated free metanephrines by enzyme immunoassay (EIA) and to evaluate its performance in the diagnosis of catecholamine-secreting tumors in the pediatric population.MethodsNormotensive children and children with suspected catecholamine-secreting tumors underwent measurement of plasma fractionated metanephrines by EIA to establish pediatric reference ranges. Children with suspected pheochromocytoma or paraganglioma also underwent magnetic resonance imaging or computed tomography from the neck to the pelvis and were followed up for a minimum of 1 year. Diagnosis of pheochromocytoma/ paraganglioma was confirmed by histologic examination. Pheochromocytoma/paraganglioma was excluded in children who had a histologic diagnosis other than pheochromocytoma/paraganglioma and in those who had no imaging evidence of tumor and no progression on follow-up.ResultsPlasma fractionated metanephrines were measured in 78 normotensive children (age range, 1.5-17 years) and in 38 children with suspected catecholamine-secreting tumors. Of the 38 children (age range, 6-17 years) with suspected pheochromocytoma/paraganglioma, 17 had a histopathologically proven catecholamine-secreting tumor. The newly derived pediatric upper reference limit for metanephrine (128 pg/mL) was higher than in adults (90 pg/mL), whereas the pediatric upper reference limit for normetanephrine (149 pg/mL) was lower than in adults (180 pg/mL). The manufacturer’s reference range for plasma fractionated metanephrines yielded a sensitivity of 100% and a specificity of 85.7%. Use of newly established pediatric reference ranges increased the specificity to 95.2% without altering the sensitivity (100%).ConclusionsPlasma fractionated metanephrines by EIA provide an accurate test with good sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma in children. Use of pediatric reference ranges improves accuracy of the test. (Endocr Pract. 2012;18:694-699)     

Quantitative measurement of plasma free metanephrines by ion-pairing solid phase extraction and liquid chromatography-tandem mass spectrometry with porous graphitic carbon column

Plasma free metanephrine and normetanephrine are the best biomarkers for diagnosing pheochromocytoma. In the past few years, liquid chromatography-tandem mass spectrometry has become the preferred technology to measure plasma metanephrine and normetanephrine because of its high sensitivity and specificity, as well as fast and simple sample preparation. In this study, we report a liquid chromatography-tandem mass spectrometry method for measuring plasma metanephrine and normetanephrine. A solid phase extraction method using ion-pairing reagent and C18 stationary phase was used for sample preparation. We tested a porous graphitic carbon column and a HILIC column for chromatographic separation, and the former one showed better resolution with no interference from plasma matrix. This method was linear from 7.2-486.8 pg/mL for metanephrine and 18.0-989.1 pg/mL for normetanephrine with an accuracy of 92.2-111.8% and 92.1-115.0%, respectively. Inter-assay and intra-assay CV for metanephrine and normetanephrine at two different concentration levels ranged from 2.0% to 10.9%. In conclusion, this liquid chromatography-tandem mass spectrometry method using ion-pairing solid phase extraction and porous graphitic column was simple and efficient for measuring plasma metanephrines.     

Urinary metanephrines by liquid chromatography tandem mass spectrometry: using multiple quantification methods to minimize interferences in a high throughput method

Determination of urinary metanephrines is requested frequently for the differential diagnosis and monitoring of pheochromocytoma. Although numerous methods have been developed, interferences are common and hinder most available assays. This study describes the development, validation and implementation of a reliable high-throughput LC-MS/MS method for the measurement of metanephrine and normetanephrine in urine. Metanephrine and normetanephrine were isolated from urine samples subjected to acid hydrolysis using solid phase extraction on a mixed mode cation exchange sorbent in 96-well format. The extracts were injected directly onto a Restek perfluorophenyl column and separated isocratically in 0.2% formic acid in 5% methanol with a gradient cleanout step to 50% methanol. Detection was accomplished using an API 3200 triple quadrupole mass spectrometer with electrospray ionization in positive mode. Data were acquired in multiple reaction monitoring mode. Three transitions were monitored for metanephrine and its deuterated internal standard; two transitions were monitored for normetanephrine and its deuterated internal standard. Two quantification methods were used to address metanephrine interferences without reducing throughput. The method was linear to 15,000 nmol/L. The limits of detection and quantification were 2.5 and 10 nmol/L, respectively. Within run, between-day and total imprecision values were at or below 1.9%, 2.5% and 2.7% for both analytes. The method correlated well with our previously used GC-MS method. Injection-to-injection time was 6 min. The validated LC-MS/MS method for measurement of metanephrine and normetanephrine in urine specimens was placed into service in August 2010 and has performed exceptionally well.     

Determination of catecholamines and metanephrines in urine by capillary electrophoresis-electrospray ionization-time-of-flight mass spectrometry

A method successfully coupling capillary electrophoretic separation to time-of-flight mass spectrometric (TOFMS) detection for the simultaneous analysis of catecholamines (dopamine, norepinephrine, and epinephrine) and their O-methoxylated metabolites (3-methoxytyramine, normetanephrine, and metanephrine) is described. The inner capillary wall was coated with polyvinyl alcohol in order to obtain baseline resolution of catecholamines and metanephrines and to ensure reproducibility without extensive restorative washing of the capillary. Using electrokinetic injection, detection limits of 0.3 microM for dopamine and norepinephrine, 0.2 microM for 3-methoxytyramine and normetanephrine, and 0.1 microM for epinephrine and metanephrine were achieved with standard solutions. The usefulness of this approach was demonstrated by applying the developed method to the analysis of a spot collection of human urine from a healthy volunteer. The catecholamines and metanephrines were removed from the urine samples and preconcentrated by simultaneous SPE on cation-exchange sorbents. The recoveries of all analytes, with the exception of epinephrine (75%), were over 80%. Catecholamines and metanephrines in the urine samples were quantitated using 3,4-dihydroxybenzylamine as an internal standard. Submicromolar concentrations, consistent with the catecholamine and metanephrine levels reported for normal human urine, were detected.     

Is Biochemical Assessment of Pheochromocytoma Necessary in Adrenal Incidentalomas with Magnetic Resonance Imaging Features not Suggestive of Pheochromocytoma?

Objective: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial.Methods: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines.Results: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences.Conclusion: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results.Abbreviations:AI = adrenal incidentalomaCT = computed tomographyMRI = magnetic resonance imaging     

Current progress and future challenges in the biochemical diagnosis and treatment of pheochromocytomas and paragangliomas.

Findings from five independent studies - with close to 350 patients with pheochromocytoma and more than 2,500 in whom the tumor was excluded - indicate that measurements of plasma free metanephrines provide an overall diagnostic sensitivity of 98% and specificity of 92%. The recommendation that initial testing for the tumor should always include measurements of either plasma or urinary fractionated metanephrines results from recognition of the high diagnostic sensitivity of measurements of plasma metanephrines. The few patients with pheochromocytoma in whom the test may not yield a positive result include those with very small tumors or microscopic disease and others with tumors that do not produce norepinephrine and epinephrine. Such patients are typically normotensive and do not exhibit symptoms of catecholamine excess. Additional measurements of methoxytyramine can be useful for detecting those tumors that produce only dopamine. Suboptimal diagnostic specificity and difficulties in distinguishing true- from false-positive elevations of plasma metanephrines remain challenges for diagnosis. Improvements in analytical technology (e.g., liquid chromatography with tandem mass spectrometry) and new strategies for follow-up testing provide possible solutions to these problems. The single most important remaining clinical care challenge is the development of effective cures for patients with malignant disease. Current treatments, none of which are truly satisfactory, include chemotherapy and radiopharmaceutical therapy with (131)I-labelled M-iodobenzylguanidine or radioactive somatostatin analogues. Improvements in treatment may in the future come from several fronts, but proof of efficacy ideally will require well-coordinated multicenter prospective trials in larger numbers of patients than in previous studies.     

Long-term postoperative follow-up in patients with apparently benign pheochromocytoma and paraganglioma

Patients with pheochromocytoma or paraganglioma are at risk of developing tumor recurrences or new tumors after successful resection of the primary tumor. This review summarizes current knowledge concerning the incidence and risk factors for such events. The overall incidence exceeds 15%. Patients with inherited tumors have a higher probability of recurrence or new tumors. Most recurrences are metastatic, particularly in patients with SDHB mutations or nonhereditary tumors. We recommend the determination of plasma or urinary metanephrines (normetanephrine and metanephrine) 1 month after surgery. In patients with sporadic, single tumors ≤5 cm in diameter, clinical and biochemical follow-up should be performed every 2 years. However, this follow-up period can be reduced to yearly, if it is more simple and more convenient for patients and physicians. Patients with larger or multiple but apparently benign tumors and/or inherited disease should be tested 6 months after surgery and then every year for the rest of their lives. Imaging follow-up is also required in patients with inherited or malignant tumors.     

Ordering Pattern and Performance of Biochemical Tests for Diagnosing Pheochromocytoma Between 2000 and 2008

ObjectiveTo examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice.MethodsIn this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed.ResultsA total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%.ConclusionsOrdering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation. (Endocr Pract. 2009;15:313-321)     

Simultaneous automatic determination of catecholamines and their 3-O-methyl metabolites in rat plasma by high-performance liquid chromatography using peroxyoxalate chemiluminescence reaction

A highly specific and sensitive automated high-performance liquid chromatographic method for the simultaneous determination of catecholamines (CAs; norepinephrine, epinephrine, and dopamine) and their 3-O-methyl metabolites (normetanephrine, metanephrine, and 3-methoxytyramine) is described. Automated precolumn ion-exchange extraction of diluted plasma is coupled with HPLC separation of CAs and their 3-O-methyl metabolites on an ODS column, postcolumn coulometric oxidation, fluorescence derivatization with ethylenediamine, and finally peroxyoxalate chemiluminescence reaction detection. The detection limits were about 3 fmol for norepinephrine, epinephrine, and dopamine, 5 fmol for normetanephrine, and 10 fmol for metanephrine and 3-methoxytyramine (signal-to-noise ratio of 3). Fifty microliters of rat plasma was used and 4-methoxytyramine was employed as an internal standard. The relative standard deviations for the method (n = 5) were 2.5-7.6% for the intraday assay and 6.3-9.1% for the interday assay. The method was applicable to the determination of normetanephrine and metanephrine in 50 microl of rat plasma.     

High-performance liquid chromatographic determination of catecholamines and their precursor and metabolites in human urine and plasma by postcolumn derivatization involving chemical oxidation followed by fluorescence reaction.

A high-performance liquid chromatographic method for the determination of catecholamines and their precursor and metabolites [amino compounds (norepinephrine, epinephrine, dopamine, normetanephrine, metanephrine, 3-methoxytyramine, and L-DOPA), acidic compounds (3,4-dihydroxyphenylacetic acid, vanillyl-mandelic acid, and homovanillic acid), and alcoholic compound [4-hydroxy-3-methoxyphenyl)ethylene glycol)] in human urine and plasma. Urine and plasma samples deproteinized with perchloric acid in the presence of isoproterenol and 3,4-dihydroxyphenylpropanoic acid (internal standards) are fractionated by solid-phase extraction on a strong cation-exchange resin cartridge (Toyopak IC-SP S) into two fractions (amine fraction and acid-alcohol fraction). The compounds in each fraction are separated by an ion-pair reversed-phase chromatography on a TSK gel ODS-80TM with isocratic elution and on-line derivatized by periodate oxidation followed by a fluorescence reaction using meso-1,2-diphenylethylenediamine. The detection limits (S/N = 5) vary from 0.5 to 95 pmol/ml, depending on the compounds.     

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)     

A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland

A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple café-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family.     

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)     

Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma.

Urinary methoxyamine determination is considered as the most sensitive and specific parameter for the diagnosis of pheochromocytoma. Since blood sampling is easier to perform, we developed a new HPLC method to assay metanephrine (MN) and normetanephrine (NMN) in plasma. We now report the results for total (free and conjugated) MN and NMN in 22 cases of pheochromocytoma compared to 26 healthy subjects, 33 patients with essential hypertension, 14 with miscellaneous diseases and 4 patients with renal failure. The mean normal values (mean +/- SD) were 0.40 +/- 0.10 ng/ml for MN and 0.85 +/- 0.25 ng/ml for NMN. The sum of MN+NMN was 1.25 +/- 0.28 and the range 0.9-1.9. In essential hypertension, the range of NMN+MN was 1.2-6.0. In the 4 renal failures, both MN and NMN were drastically increased. In 49 samples drawn from 22 pheochromocytomas, MN was elevated over the hypertensive range in 34 samples and NMN in 47 samples. The total MN+NMN ranged from 6.2 to 436 ng/ml; this figure was observed whatever the clinical presentation even in silent tumors or in paroxysmal forms between the crisis. After tumor removal, the values dropped rapidly. In conclusion, plasma determination of MN and NMN provides a highly sensitive and specific biological pointer for the diagnosis of pheochromocytoma in patients without renal failure.     

Pheochromocytoma And Pregnancy:A Rare But Dangerous Combination

ObjectiveTo review the literature on pheochromocytoma in pregnancy (PIP) published during the 11-year period 1998 through 2008.MethodsWe searched MEDLINE data sources from 1998 through 2008 using the search terms “pheochromocytoma” and “pregnancy” and reviewed case reports of PIP published in English.ResultsWe identified 54 case reports in MEDLINE data sources, of which 51 reports including 60 cases were reviewed. In comparison with the previous decade, a decreased rate of antenatal diagnosis (from 83% to 70%) and increased maternal and fetal mortality (from 4% to 12% and from 10% to 17%, respectively) were observed. Prematurity was present in 53% of the infants of mothers with antenatally diagnosed pheochromocytoma who gave birth to a live infant. Hypertension was the most common manifestation (88%), with 33% of patients having antepartum hypertensive crises. Urinary catecholamines (64%) and metanephrines (40%) were the most commonly used tests, whereas urinary and plasma metanephrines were the most sensitive tests (100%). Ultrasonography had poor sensitivity (54%), especially during the third trimester. Magnetic resonance imaging was 100% sensitive for adrenal tumors but had only 50% sensitivity for extra-adrenal tumors. A syndromic or familial presentation was seen in 18% of patients, and 32% of patients had bilateral or extraadrenal tumors.ConclusionIn comparison with the previous decade, a decreased rate of antenatal diagnosis and increased maternal and fetal mortality were observed. Prematurity was a major morbidity associated with PIP. Hypertensive crises were more common during pregnancy. Urinary and plasma metanephrines had the highest sensitivity to detect PIP. Genetic screening should be offered to all pregnant women with pheochromocytoma. (Endocr Pract. 2010;16:300-309)     

Plasma Free Metanephrine and Normetanephrine Levels are Increased in Patients with Chronic Kidney Disease

ObjectivePatients with impaired renal function, particularly those on dialysis, frequently exhibit high blood pressure and hemodynamic instability, which often lead to pheochromocytoma assessment. Our objective was to assess plasma free metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients (CKD) with or without dialysis.MethodsIn this prospective observational study we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30 patients with histologically proven pheochromocytoma, and 43 hypertensive patients. Adrenal masses were ruled out by abdominal computed tomography (CT) scans in all CKD and control hypertensive patients.ResultsAll 3 CKD groups (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and NMN levels than the control hypertensive group (P < .0055). HD and CAPD patients had significantly lower plasma free NMN (P < .0055), but free MN levels were not significantly different than those observed in pheochromocytoma patients. In patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were higher than manufacturer’s upper limits of normal in 57.7% and 28.5%, 13.3% and 61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the number of dialysis years was significantly correlated with plasma free MN (r = 0.615, P < .001) but not free NMN.ConclusionPlasma free MN and NMN levels are frequently elevated in CKD patients, particularly in those on dialysis. Plasma free MN levels significantly overlap with the range in pheochromocytoma patients and correlate with the number of years on dialysis. (Endocr Pract. 2014;20:139-144)     

Transthoracic needle aspiration biopsy. Review of 233 cases

In 233 cases in which transthoracic needle aspiration was done at the Mayo Clinic from 1980 through 1983, the cytology slides, tissue fragments and patient histories were reviewed; the original and review diagnoses were compared and correlated with the subsequent clinical course. In most cases, the procedure was performed with an 18-gauge needle under fluoroscopic guidance, primarily in cases with suspected malignant masses that were considered to be not surgically resectable. In 70% of the cases, there was a history of malignancy, and 82% of the malignant lesions were of extrapulmonary origin. Correlation of the original diagnosis with the clinical course yielded 70% (164 cases) true positives, 6% (14 cases) true negatives, 16% (37 cases) false negatives, 0% false positives and 8% (18 cases) indeterminants. In none of the false-negative cases was the slide subsequently read as positive in a blind review. Of the true-positive cases, 12% had positive tissue fragments only, 37% had positive cytology smears only, and 51% had both positive smears and fragments. In 32% of the cases, there were radiologically demonstrable pneumothoraces, and in 12%, placement of a chest tube was required. Hemoptysis occurred in less than 5% of the cases. In summary, transthoracic needle biopsy provides an efficient way to accurately obtain diagnostic tissue, with acceptable minor complications.     

Pheochromocytoma-Induced Aggression?

ObjectiveTo document a case of pheochromocytoma with an unusually high plasma ratio of norepinephrine to epinephrine concentrations (NE:E), and a history of violent and aggressive behavior (which has been reported to be associated with increased NE:E ratios).MethodsWe present the history of present illness, history of aggressive behavior, and the clinical course of a man who was found to have pheochromocytoma with a remarkable catecholamine profile. We also review the literature on the relationship of catecholamine ratios to behavior.ResultsA 33-year-old man presented to the emergency department with the chief complaint of palpitations and chest pain. A physical exam revealed markedly elevated blood pressure. On admission, a computed tomographic scan of the abdomen revealed a 10 by 10-cm heterogeneous mass of 20 Hounsfield units superior to the right kidney. His plasma NE:E ratio was 35, and his 24-hour urine ratio of normetanephrine to metanephrine concentrations was greater than 26. The tumor was successfully removed with laparoscopic adrenalectomy, and the histologic findings revealed benign pheochromocytoma. There was no immediate change in the patient’s behavior. He was incarcerated the week after surgery, and lost to follow-up.ConclusionPrimarily norepinephrine-producing pheochromocytoma may have contributed to this patient’s violent and aggressive behavior. Catecholamine levels may remain elevated for 1 week following surgery. Even if this patient’s norepinephrine level had dropped rapidly after removal of the pheochromocytoma, and was not elevated a week later when he was arrested, it is possible that his aggressive behavior may have been conditioned by long exposure to elevated levels of norepinephrine. (Endocr Pract. 2011;17:e126-e129)     

Diagnostic difficulties in adrenal incidentaloma--analysis of 125 cases

INTRODUCTION: Therapeutic approach to incidentaloma, in spite of existing algorithms, is not always obvious due to diagnostic difficulties. The aim of the study was to assess the validity of the initial diagnoses of incidentaloma which determined the qualification for the operation. MATERIAL AND METHODS: 125 patients hospitalised in the Endocrinology Dept. of the Medical University of Bialystok in the years 2003-2005 and in the Endocrinology dept. of Voivodeship Hospital of Bialystok. The patients were clinically and hormonally examined (metanephrines in daily urine collection, daily cortisol rhythm, short dexamethasone test, aldosterone, and renin plasma activity, Na, K levels in the serum) as well as computer tomography of the adrenal glands were performed. RESULTS: 42 patients were qualified for adrenalectomy. Adenoma was confirmed in 25 patients (in 7 subclinical Cushing syndrome was diagnosed, in 2 Conn disease, in 16 inactive changes), phaeochromocytoma in 6 patients, cysts in 3, lipoma in 2, carcinoma in one, in 4 patients metastases (in 2 of kidney carcinoma, in 1 of malignant melanoma and in 1 of planocellular carcinoma) and in one oncocytoma. Metanephrines urine measurements showed 33% of false positive results. CONCLUSIONS: Qualification for adrenalectomy requires an assessment of tumor's enlargement, its tissue density, morphology and growth dynamics. To reduce the percentage of false positive results of metanephrine measurement there is to eliminate an influence of some drugs, victuals, beverages and nicotine and eventually to carry out additional tests. The decision as to proceeding with adrenal incidentaloma should be individualized based on clinical symptoms, hormonal tests and tumor morphology.