Urinary Catecholamine Excretion Research Articles

Predicting Posttraumatic Stress Symptoms From Pretraumatic Risk Factors: A 2-Year Prospective Follow-Up Study in Firefighters

Most studies focusing on risk factors for posttraumatic stress disorder (PTSD) have used retrospective study designs. Only a small number of studies have prospectively examined risk factors in the immediate aftermath of trauma exposure in predicting PTSD symptoms. The purpose of this study was to identify predictive risk factors for posttraumatic stress symptoms and comorbid psychopathological symptoms present during the time before exposure to traumatic stress in a high-risk population. Forty-three professional firefighters were assessed immediately after basic training (baseline) and at 6, 9, 12, and 24 months after entry into firefighter service. Subjects were screened for psychopathological symptoms, including symptoms of PTSD, depression, and anxiety. Subjects were also characterized with regard to personality traits such as self-efficacy, hostility, and alexithymia. Neuroendocrine activity was assessed by examination of awakening and diurnal salivary cortisol profiles and 24-hour urinary catecholamine excretion. Multiple linear regression analysis was used to analyze posttraumatic stress symptoms at 24-month follow-up as a function of pretraumatic characteristics. A high level of hostility and a low level of self-efficacy at baseline accounted for 42% of the variance in posttraumatic stress symptoms after 2 years. Subjects who had both risk factors at baseline showed a significant increase in measures of PTSD symptoms, depression, anxiety, general psychological morbidity, global symptom severity, and alexithymia during the 2-year period. Biological characteristics were not predictive of the development of psychopathological symptoms. These results suggest that specific personality traits may constitute markers of vulnerability to the development of psychopathological symptoms after trauma exposure. Early identification of preexisting risk factors is needed to provide effective prevention and intervention for individuals who are at risk of developing trauma-related disorders.

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy

To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.

Myocardial Electric Instability and Catecholamine Excretion in Urine

To study structure of heart rate disturbance (HRD) in relation to stage of sympathoadrenal system (SAS) activation on 10-12 day QMI. In 34 men with QMI, HRD was studied on Holter ECG (Lown-Wolf), SAS was evaluated by excretion of epinephrine (E), norepinephrine (NE) and dofamin (D) in daily urine. In group (G) I (n=20) E excretion was 3 times higher, than in GII, (p<0,001), differences in excretion NE and D were n.s. Dispersion Q-T was 1,5 times higher in GI (p<0,05). The frequent ventricle extrasystoles (VE) were revealed in 21% and in 7%, (p>0,05), polymorphic VE in 35% and 7%, (p<0,05), and VE iva,b in 60% and 14% of patients, (p<0,05). Complex ventricular arrhythmias (CVA) were noted in 60% and 21% of patients in GI and GII, (p<0,05). Supraventricular (SV) HRD were revealed in 60% and 50% of the patients in GI and GII, (p>0,05). Association of CVA and SVHRD were found in 45% and 7%, (p<0,05). In GI with SAS activation there were observed increase in Q-T dispersion, CVA and cases of its combination with VHRD.

Composite paraganglioma–ganglioneuroma of the urinary bladder

Presented herein is the case of a 73-year-old man, complaining of dysuria, who had a composite paraganglioma-ganglioneuroma of the urinary bladder (CPGUB). At cystoscopy a submucosal tumor was found in the urinary bladder and resected after transurethral biopsy. The levels of serum catecholamine and 24 h urinary excretion of catecholamine and vanillylmandelic acid were elevated. Grossly, the resected tumor, measuring 4 x 3 x 2.5 cm, had a brownish cut surface with no necrosis and hemorrhage. Histologically, the tumor had alternating cellular and fibrous areas. The cellular areas consisted of polygonal cells, arranged in well-defined nests (Zellballen) and positive for Grimelius staining, with abundant amphophilic to acidophilic cytoplasm, occasionally containing eosinophilic hyaline globules and brown pigments. Although the nuclei of several polygonal cells were bizarre, mitoses and vascular invasion were not found. Fibrous areas consisted of spindle cells, resembling Schwann cell, admixed with ganglionic cells. To the authors' knowledge, only four cases of CPGUB have been reported in the English-language literature. Detailed reported cases and the present case showed no malignant features, such as extra-bladder infiltration and metastasis, and no recurrence in the short length of follow up. Accumulation of long-term follow-up cases may provide valuable prognostic information on this composite tumor.

24-hr Urinary Catecholamine Excretion, Training and Performance in Elite Swimmers

The aim of the present study was to investigate the effects of training variations on 24-hr urinary noradrenaline (NA) and adrenaline (Ad) levels and the adrenaline/noradrenaline (Ad/NA) ratio to search for a possible relationship between catecholamine excretion, training, and performance in highly trained swimmers. Fourteen swimmers (5 female and 9 male) were tested after 4 weeks of intense training (IT), 3 weeks of reduced training (RT), and 5 weeks of low training (LT). At the end of each period, the swimmers performed their best event at an official competition. Individual performances were expressed as percentage of the previous season's best performance. The changes in NA levels after 4 weeks of IT were negatively related to changes in training volume (r=-0.70, p<0.01) and total training load (r=-0.68, p<0.02). NA levels measured at the end of IT were positively related to changes in performance after three weeks of RT (r=0.77, p<0.01). The percentage changes in performance between RT and LT were related to NA levels at the end of RT (r=0.60; p<0.04). Ad/NA ratios and Ad were related to performance (r=0.58, p<0.01; r=52, p<0.01; respectively). The differences in Ad/NA ratios and Ad between two consecutive competitions were related to the differences in performance (r=0.59, p<0.01; r=0.49, p<0.01; respectively). 24-hr NA and the Ad/NA excretion ratio were related to both training variations and performance. Thus, 24-hr NA levels and Ad/NA ratio may provide useful markers for monitoring training stress in elite swimmers.

Attenuation of Diet-Induced Weight Gain and Adiposity through Increased Energy Expenditure in Mice Lacking Angiotensin II Type 1a Receptor

Given that angiotensin II (AII) type 1 and 2 receptors (Agtr1 and Agtr2) are expressed in adipose tissue, AII may act directly on adipose tissue. However, regardless of whether AII directly modulates adipose tissue growth and metabolism in vivo and, if so, whether it is mediated via Agtr1 are still matters of debate. To understand the functional role of Agtr1 in adipose tissue growth and metabolism in vivo, we examined the metabolic phenotypes of mice lacking Agtr1a (Agtr1a-/- mice) during a high-fat diet. The Agtr1a-/- mice exhibited the attenuation of diet-induced body weight gain and adiposity, and insulin resistance relative to wild-type littermates (Agtr1a+/+ mice). They also showed increased energy expenditure accompanied by sympathetic activation, as revealed by increased rectal temperature and oxygen consumption, increased expression of uncoupling protein-1 mRNA in brown adipose tissue, and increased urinary catecholamine excretion. The heterozygous Agtr1a-deficient mice (Agtr1a+/- mice) also exhibited metabolic phenotypes similar to those of Agtr1a-/- mice. Using mouse embryonic fibroblasts derived from Agtr1a+/+ and Agtr1a-/- mice, we found no significant difference between genotypes in the ability to differentiate into lipid-laden mature adipocytes. In primary cultures of mouse mature adipocytes, AII increased the expression of mRNAs for some adipocytokines, which was abolished by pharmacological blockade of Agtr1. This study demonstrates that Agtr1a-/- mice exhibit attenuation of diet-induced weight gain and adiposity through increased energy expenditure. The data also suggest that AII does not affect directly adipocyte differentiation, but can modulate adipocytokine production via Agtr1.

Effect of 4 weeks of basic military training on peripheral blood leucocytes and urinary excretion of catecholamines and cortisol

In this study, we assessed the effects of a 4 week basic military physical training programme for male recruits of the Hellenic Air Force on the number and distribution of circulating immune cells and adrenergic and adrenocortical hormonal responses. One group of recruits (exercised, n = 48) participated in moderate intermittent physical exercise, whereas a second group (non-exercised controls, n = 9) performed only light work in the barracks. Both groups participated in the same non-physical, classroom-type training and testing. Military training by the exercised group resulted in significant increases in CD4 + T-lymphocytes, renal cortisol excretion and the urinary noradrenaline/adrenaline ratio, together with reductions in neutrophils and the neutrophil/lymphocyte ratio. In the exercised group, the urinary noradrenaline/adrenaline ratio correlated positively with the training-induced changes in CD4 + T-lymphocytes and negatively with changes in the neutrophil/lymphocyte ratio. No significant relationship was found between training-induced increases in cortisol excretion and any of the peripheral blood cell alterations. Our results indicate that 4 weeks of military training consisting of intermittent moderate exercise resulted in a significant increase in CD4 + T-lymphocytes and reduction in neutrophils. These changes were probably driven by alterations in hormonal status, including the significant impact of sympathetic nervous system activation.

タンパク質摂取レベルの変化が尿中カテコールアミン排出に及ぼす影響

It has been suggested that a low protein intake causes sustained enhancement of sympathetic nervous activity. Thus, the present study was undertaken to see the effects of different sizes of protein intake under a constant daily energy intake (1,600 kcal/day), on urinary excretions of catecholamines and their metabolite, vanylmandelic acid (VMA), in healthy young women. In the experiment 1, in which 40g- and 80g-protein containing food were taken for 4 days and 8 days, respectively, VMA excretion decreased after 80g-protein intake. In the second experiment, 40g-, 80g-and 40g-protein containing food were successively taken for 4 days, respectively. In here, dopamine (DA) excretion increased significantly after 80g-protein intake, and returned to the initial level by retaking of 40g-protein containing food. Noradrenaline (NA) excretion did not change after 80g-protein intake. NA/DA ratio decreased significantly after 80g-protein intake, and returned to the initial level after the second 40g-protein intake. VMA excretion tended to decrease successively during the 80g-and the following 40g-protein intake periods. The present results indicate that the conversion of DA to NA may be suppressed by a excess protein intake, and that the enhanced sympathetic nervous activity observed in the lean subjects, could be caused, at least in part, by a lower protein intake by them.

痩身者の高タンパク摂取による尿中カテコールアミン排出への影響

痩身者の高タンパク摂取による尿中カテコールアミン排出への影響

Abstracts

Abstracts

Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women

Objective Depression is a risk factor for morbidity and mortality in a variety of populations, and anxiety has also been associated with risk of mortality among cardiac patients. Dysfunction of the autonomic nervous system may be involved in this risk. The primary goal of this study was to evaluate the relationship between levels of self-reported symptoms of depression and anxiety and 24-hour urinary catecholamine excretion. Method Ninety-one women aged 47–55 years were evaluated. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and state anxiety was assessed with the state anxiety portion (SAI) of the Spielberger State–Trait Anxiety Inventory (STAI). Twenty-four hour urine collections were assayed for epinephrine (EPI), norepinephrine (NE) and cortisol (CORT). EPI, NE and CORT were indexed by body surface area to control for individual differences in body size. Results Higher levels of depression symptoms were associated with increased 24-hour NE excretion ( r=.27, P=.009), with depressed women ( n=17, BDI scores ≥10) exhibiting an approximately 25% higher rate of urinary NE excretion than women with BDI scores <10 ( n=74), P=.007. Higher levels of state anxiety were also related to greater NE excretion ( r=.28, P=.01), and CORT excretion was related to both depression ( r=.23, P=.02) and anxiety ( r=.22, P=.04). Depression and anxiety symptoms were unrelated to urinary EPI excretion. Conclusions The current findings that higher levels of depression and anxiety symptoms are related to increased 24-hour urinary NE and CORT excretion among women suggests that depression and anxiety may be associated with increased sympathetic nervous system (SNS) activity, and are consistent with the possibility that SNS activity may play a role in the increased mortality associated with depression in community-dwelling older adults.

Hostility is related to blunted beta-adrenergic receptor responsiveness among middle-aged women.

Based on previous findings in men, the hypothesis that hostility would be associated with blunted responsiveness of cardiovascular beta-adrenergic receptors was tested in a study sample of middle-aged women. The roles of the sympathetic nervous system and of social support in this putative relationship were also evaluated. Subjects were 80 healthy women (n = 23 African American; n = 57 white), aged 47 to 55 years. Hostility was assessed using the Cook-Medley Hostility Scale and social support was assessed with the Brief Social Support Questionnaire. Intravenous isoproterenol challenge was used to evaluate cardiac and vascular beta-adrenergic receptor responsiveness. Twenty-four-hour urinary catecholamine excretion was used to index sympathetic nervous system activity. Hostility was related to blunted cardiac (R = 0.33, p <.01) and vascular (R = 0.23, p <.05) beta-adrenergic receptor responsiveness in simple correlation analysis and in hierarchical regression analyses controlling for race, menopausal status, weight, and resting heart rate. Low social support was also related to blunted beta-adrenergic receptor responsiveness (R = 0.3, p <.01). Twenty-four-hour norepinephrine excretion was related both to hostility (R = 0.32, p <.01) and to cardiac (R = 0.25, p <.05) and vascular (R = 0.24, p <.05) beta-adrenergic receptor responsiveness. These observations replicate and extend previous findings in men by demonstrating that higher levels of hostility and low levels of social support are associated with blunted beta-adrenergic receptor responsiveness in middle-aged women. They also suggest that heightened sympathetic nervous system activity associated with hostility may contribute to beta-adrenergic receptor blunting. Because blunted beta-adrenergic receptor sensitivity is a characteristic feature of a broad range of cardiovascular diseases, these findings may reflect an early preclinical manifestation of pathophysiology accompanying hostility and low social support.

Relationship between overnight neuroendocrine activity and morning haemostasis in working men.

Sustained effects of SNS (sympathetic nervous system) and HPAA (hypothalamic-pituitary-adrenal axis) hyperactivity on haemostasis have not been investigated. In the present study, we tested for an association of overnight urinary catecholamine and cortisol excretion with morning plasma levels of fibrinogen, PAI-1 (plasminogen activator inhibitor-1) and D-dimer. Participants (639 male industrial employees) with a complete dataset were studied (age, 41+/-11 years; mean+/-S.D.). Subjects collected overnight urinary samples and had a fasting morning blood sample drawn. Measurement of urinary adrenaline (epinephrine), noradrenaline (norepinephrine) and cortisol were dichotomized to perform multivariate analyses of (co)variance. Haemostatic parameters were measured by ELISA. Fibrinogen was higher in men with high adrenaline (F(7,631)=5.68, P=0.018; where the subscripted value represents the degrees of freedom) and high noradrenaline (F(7,631)=4.19, P=0.041) compared with men with low excretion of the respective hormones. PAI-1 was higher in men with high cortisol than in men with low cortisol (F(7,631)=4.77, P=0.029). Interaction revealed that subjects with high cortisol/low noradrenaline had higher PAI-1 than subjects with low cortisol/high noradrenaline (P=0.038). Subjects with high adrenaline/high noradrenaline had higher D-dimer than subjects with high adrenaline/low noradrenaline (P=0.029), low adrenaline/high noradrenaline (P=0.022) and low adrenaline/low noradrenaline (not significant). When covariance for several confounders of haemostatic function was determined, the main effect of adrenaline on fibrinogen and the interaction between adrenaline and noradrenaline for D-dimer maintained significance. Although overnight SNS hyperactivity was associated independently with morning hypercoagulability, the relationship between the activity of HPAA and haemostasis was mediated by traditional cardiovascular risk factors.

Heart rate variation and urinary catecholamine excretion in response to acute psychological stress in hand-arm vibration syndrome patients.

The aim of this study was to evaluate heart rate variation and urinary catecholamines in response to acute psychological stress in hand-arm vibration syndrome (HAVS) patients and healthy controls. LF% (indicator of both the sympathetic and parasympathetic nervous activity), HF% (indicator of the parasympathetic nervous activity) and their ratio LF/HF (indicator of sympathovagal balance) were calculated from short-term electrocardiographic data from 16 HAVS patients and 14 healthy controls before and immediately after exposure to acute psychological stress. Urinary catecholamines (norepinephrine, epinephrine and dopamine) were analyzed from urine samples collected from every subject during rest and after exposure. The LF% and LF/HF of the patients significantly increased after exposure. The after exposure LF/HF of the patients was significantly greater than that of the controls. The amount of norepinephrine in the patients significantly increased after exposure. The after exposure amount of norepinephrine and epinephrine in the patients were significantly greater than the respective amount of the controls. The results of the present study indicated the predominance of sympathetic tone in the cardiac sympathovagal balance and greater sensitivity of the sympathoadrenal medullary system in response to acute psychological stress in the patients than in the healthy controls.

Effects of barefoot habituation in winter on thermal and hormonal responses in young children--a preliminary study.

This study investigated how socks-wearing habit or habitual barefoot in the cold winter affected skin temperatures of distal lower extremities, the urinary excretion of adrenaline, noradrenaline and cortsisol in young children. In Experiment I for preschool children, the measurements of foot and leg skin temperatures were conducted for 30 min in the classroom controlled at 23+/-2 degres C and 50+/-5%RH, and the excretion of urinary catecholamines and cortisol during nocturnal sleep were analyzed. In Experiment II for elementary school children, nocturnal secretion of urinary catecholamines and cortisol was analyzed. While leg skin temperature tended to be lower in barefoot group than in socks group during Experiment I, foot skin temperature was not significantly different between the two groups. Fall of leg skin temperature during 30 min measurement tended to be smaller in barefoot group than in socks group. Urine volume and urinary excretion of cortisol tended to be greater in barefoot group than in socks group for preschool children. Urinary noradrenaline was significantly greater and cortisol tended to be greater in barefoot group than in socks group for elementary school children. Considering that most of the findings shown above were in the proximity of the established level of statistical significance, it was provisionally concluded that young children with barefoot habituation might show more effective cold adaptation of metabolic type than those without the habituation do, by keeping their skin temperatures higher even in the cold and enhancing the metabolic rate.

Job strain and physiological stress responses in nurses and nurse's aides: predictors of daily blood pressure variability.

Job strain has been implicated in risk of cardiovascular disease, and there is evidence for increased blood pressure among men with job strain. It is unclear, however, to what degree job strain affects blood pressure in women. This study examined the relationships between job strain, norepinephrine and epinephrine excretion in the workplace, and ambulatory blood pressure variability during waking hours in women working as nurses or nurse's aides in Hilo, Hawaii. Women from two ethnic groups, Filipino-Americans (n = 36) and Euro-Americans (n = 23), were measured on a workday, urinary catecholamine excretion and ambulatory blood pressure being measured over a 4-h period at work and home, and overnight over an 8-h period. The rates of catecholamine excretion were measured in timed urine samples using high-performance liquid chromatography with electrochemical detection, and ambulatory blood pressure was measured at 15-min intervals using a SpaceLabs 90207 monitor. The women filled out the Job Content Questionnaire prior to the physiological measurements. Scores on the Job Content Questionnaire were not significantly associated with the physiological measures, although correlations were higher for Euro-American participants than Filipino-Americans. Catecholamine excretion rates in the workplace were significantly related to blood pressure variability throughout the day and to systolic blood pressure means, but catecholamine excretion rates in other daily settings were not significantly related to blood pressure. These results support the idea that stress in the workplace has special significance for the prediction of cardiovascular health risk, and that catecholamine excretion at work is significantly associated with increased blood pressure variability during the day. Job strain, as measured by subscales from the Job Content Questionnaire, was not associated with any of the physiological measures. This lack of association may be the result of ethnic and circumstantial bias in the questionnaire, suggesting that job strain should be evaluated in a more critical manner in populations differing from the ones in which the concept was developed.

Defect in epinephrine production in children with craniopharyngioma: functional or organic origin?

Despite pituitary hormone replacement, patients with craniopharyngioma often complain of fatigue. They may have deficient control of catecholamine secretion caused by hypothalamic lesion. Another hypothesis is a functional defect in catecholamine production through either glucocorticoid deficiency because high intraadrenal glucocorticoid concentration is necessary for epinephrine synthesis or unrecognized hypoglycemia, which can intrinsically alter epinephrine secretion. We measured catecholamine response to insulin-induced hypoglycemia and orthostasis, and 24-h urinary catecholamine excretion, in 16 children with craniopharyngioma (patients) and 27 sex- and age-matched short children. We also studied the influence of a 4-fold increase in the usual daily dose of hydrocortisone on catecholamine excretion (50 vs. 12 mg/m(2) of body surface area) in the glucocorticoid-deficient patients. Last, we compared 24-h continuous sc glucose in patients and 10 sex- and age-matched healthy children. The results are expressed as medians (25th, 75th). For a similar blood glucose nadir after insulin administration, peak plasma epinephrine in response to hypoglycemia was lower in patients vs. controls [420 (120, 715) vs. 730 (460, 1200) ng/liter, P < 0.01], whereas peak plasma norepinephrine was higher [390 (280, 550) vs. 270 (180, 280) ng/liter, P < 0.05]. Catecholamine response to orthostasis did not differ between groups. Urinary epinephrine was significantly lower in patients (P < 0.001), whereas urinary norepinephrine was similar. The extent of epinephrine deficiency correlated with neither tumor size nor hypothalamic involvement. A 4-fold higher hydrocortisone dose did not correct the defective epinephrine excretion in the glucocorticoid-deficient patients. Last, the 24-h sc glucose values were similar between patients and controls. In conclusion, children with craniopharyngioma have a defect in epinephrine but not norepinephrine production. There is no proof of a univocal origin, either organic or functional. Whether abnormal catecholamine secretion alters glucose level during fasting or acute illness, or hampers adaptation to exercise, requires further studies.

Clinical review 164: The laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic experience.

P a catecholamine-producing tumor arising in the adrenal medulla, has an estimated incidence of two to eight cases per million persons annually (1, 2). Its clinical hallmark is sustained or intermittent hypertension often associated with paroxysmal symptoms (3). Pheochromocytoma should also be considered if a patient has labile hypertension, hypertension resistant to antihypertensive therapy, or paroxysmal symptoms (“spells”) (3, 4). Correct diagnosis is important because resection of the tumor dramatically reverses the clinical symptoms and may cure the hypertension (5). A missed or delayed diagnosis may cause considerable morbidity and mortality (5, 6). Clinically significant pheochromocytoma was first recognized in 1926 when Cesar Roux in Switzerland and Charles H. Mayo in the United States successfully removed pheochromocytomas to cure the catecholamine-associated symptom complex (7, 8). A biochemical assessment of catecholamine hypersecretion was not possible in 1926. Since then, the diagnostic approach has progressed from clinical impressions and exploratory laparotomies to histamine stimulation and phentolamine suppression tests in the 1940s, crude catecholamine measurements and iv urograms in the 1950s and 1960s, and refined measurements of catecholamine levels and computerized imaging in the 1970s and 1980s. Most laboratories now measure catecholamines by HPLC with electrochemical detection or gas chromatography and mass spectrometry. Catecholamines and their metabolites can be measured in the blood or urine. There are major regional, institutional, and international differences in the approach to the biochemical diagnosis of pheochromocytoma. For example, at Mayo Clinic, physicians have relied on the 24-h urinary excretion of catecholamines and total metanephrines for more than 2 decades (9, 10). If the baseline 24-h urinary studies are normal, the study is repeated when the patient is symptomatic (e.g. with a spell). From 1976–1993, Mayo Clinic clinicians performed histamine and glucagon stimulation tests (with measurement of blood pressure and plasma fractionated catecholamines) in 542 patients in whom pheochromocytoma was highly suspected despite normal 24-h urinary catecholamine or total metanephrine excretion; none of these patients had a positive stimulation test in this setting (11). Thus, we did not find the addition of histamine and glucagon stimulation tests helpful after 24-h urinary testing. The most recent addition to the biochemical testing armamentarium is fractionated plasma free metanephrines, a test proposed to be the superior to urinary testing by some investigators (12, 13). Herein, we focus on the biochemical tests used to diagnose sporadic adrenal pheochromocytoma. To provide perspective, two datasets from Mayo Clinic are summarized: 1) historical data before the use of fractionated free plasma metanephrines (1978–1996), and 2) current data obtained after the introduction of fractionated free plasma metanephrines (after 1998).

Retrospective analysis of abnormal 24-h urinary free catecholamine concentration in screening for phaeochromocytoma.

Patients with hypertension often have increased 24-h excretion of urinary free catecholamines (UFCA) compared with normotensive patients, but the extent to which beta-blockade and other antihypertensive agents affect 24-h UFCA concentrations remains unclear. Consequently, many patients with slightly elevated 24-h UFCA concentrations are not adequately investigated for the presence of phaeochromocytoma. We undertook a retrospective study on patients with at least one abnormal 24-h urinary collection of adrenaline (Adr), noradrenaline (NA) or dopamine (DA) between July 1997 and December 1999 to assess these issues. Of the 168 patients identified with raised 24-h UFCA concentrations, 106 with hospital notes were audited. Of the 46 patients whose values were more than twice the upper reference limit, 24 had their result confirmed with a repeat sample and only 10 underwent computed tomography or m-iodobenzylguanidine scanning. Two patients of these 10 had a phaeochromocytoma. We observed that hypertension correlated with significantly increased NA excretion compared with normotensive patients (median value 490+/-222 nmol per 24 h versus 304+/-229 nmol per 24 h, P<0.005). Patients on beta-blockers showed a trend towards significantly increased NA excretion (P=0.08). Many patients with abnormal 24-h UFCA excretion are not thoroughly investigated for the presence of phaeochromocytoma. NA concentration is significantly raised above the reference limit for patients with hypertension, and the use of beta-blockers showed a trend towards a further elevation in NA concentrations. Care must therefore be taken when interpreting abnormal NA concentrations in patients with hypertension or in those taking beta-blockers.

Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas.

Serotonin is the principal endocrine product of carcinoid tumors, but simultaneously increased production of catecholamines has been described in these tumors. As it is not clear whether these tumors contain specific enzymes for catecholamine synthesis, we aimed to detect catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT)] in midgut carcinoid tumors and pheochromocytoma and to correlate enzyme expression to serotonin production as well as catecholamines and metabolites excreted in urine. Paraffin-embedded tumor specimens from 21 midgut carcinoid patients and 20 pheochromocytoma patients (10 sporadic and 10 MEN type IIa-related tumors) were stained for TH, DBH, and PNMT, using a three-step biotin-avidin-peroxidase method. TH was demonstrated in 9 (43%) of 21 carcinoids and in all (100%) of 20 pheochromocytomas, DBH in 8 (38%) carcinoids and in 15 (75%) pheochromocytomas, and PNMT in 7 (33%) carcinoids and in 13 (65%) pheochromocytomas. Increased urinary excretion of catecholamines and metabolites was observed in 10 (48%) carcinoid patients and in all pheochromocytoma patients. No clinically relevant association between enzyme expression and urinary excretion of catecholamines and metabolites was found. Catecholamine-synthesizing enzymes are present in many carcinoid tumors. This finding possibly indicates the existence of a catecholamine-synthesizing pathway in carcinoids similar to that found in pheochromocytoma.