Urinary Metanephrine Excretion Research Articles

Sleep reactivity to stress and insomnia: sleep measures and molecular markers

Objective. To identify objective measures of sleep and molecular markers of sleep reactivity to stress to determine its role for insomnia prevention and management. Design and methods. The sample included 42 subjects with sleep disturbances and 23 subjects without sleep-related complaints (control group) aged 18 to 72 years. Altogether there are 19 men and 55 women. Nine participants were excluded from the study. Sleep reactivity to stress was assessed using the Ford Insomnia Response to Stress Test (FIRST) questionnaire. The Integrative Anxiety Test was used to screen for anxiety. Sleep indices were assessed by polysomnography (PSG). Blood plasma samples were collected in the morning after PSG to determine brain-derived neurotrophic factor (BDNF), and 24-hour urine was collected one week after PSG to assess metanephrine levels. Results. There were 64 % healthy subjects with low sleep reactivity to stress and low anxiety and 79 % subjects showed insomnia among persons with high sleep reactivity and anxiety. Significant differences in PSG measures were found in groups with low and high sleep reactivity: the efficiency of sleep and the percentage of the second stage of NREM sleep were higher in group with low reactivity, also sleep latency and wake time after sleep onset were lower in group with high reactivity. In addition, serum BDNF level was significantly higher in group with low reactivity, and it correlates positively with daily urinary metanephrine excretion and the absolute duration of stage N3 and negatively with sleep latency. Conclusions. Subjects with high reactivity to stress have lower sleep quality and depth that corresponds to other studies. The level of BDNF is a possible marker of sleep reactivity to stress and it can indicate the potential adaptation to stress.

Clinical, imagingand biochemical presentationof cystic pheochromocytomas.

Cystic adrenal mass is a rare imaging presentation of pheochromocytoma. We aimed to describe the clinical, biochemicaland imaging characteristics of patients with cystic pheochromocytoma. Single-centre, retrospective study, 2000-2020. Consecutive patients with cystic pheochromocytoma were identified from our institutional pathology and adrenal tumour database. Of the 638 patients with pheochromocytomas, 21 (3.2%) had cystic pheochromocytomas (median age: 57 years, 57% women). Most pheochromocytomas were discovered incidentally (57%) or due to symptoms of catecholamine excess (24%). The median tumour size was 6.4 cm. On imaging, cystic pheochromocytomas were round or oval (90%), heterogeneous lesions (86%) with a thick solid rim (median rim thickness 13.9 mm, unenhanced computed tomography (CT) attenuation 40 Hounsfield units(HU), venous-phase CT attenuation 83 HU), and a median cystic component of 40% (unenhanced CT attenuation 17.6 HU, venous-phase CT attenuation 20.4 HU), and rarely with calcifications (15%). All 20 patients with biochemical testing had functioning tumours (adrenergic in 80%, noradrenergic in 20%). Total urinary metanephrine excretion correlated with the volume of the solid component (R2 = .75, p < .0001) but not the cystic component (R2 = .04, p = .4386). All patients underwent adrenalectomy (48% laparoscopic, 52% open), and the median duration of hospital stay was 4 days. Cystic pheochromocytomas are rare, large tumours with a phenotypic appearance that can masquerade as other adrenal cystic lesions. The degree of biochemical abnormality in cystic pheochromocytomas is associated with the volume of the solid component. All patients with adrenal cysts that have a solid component or an unenhanced attenuation >10 HU should undergo biochemical testing for pheochromocytoma.

Вплив багатокомпонентної терапії на діастолічну функцію лівого шлуночка в пацієнтів з резистентною артеріальною гіпертензією

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

Sympathoadrenal activity and sleep: in the search for a marker of hyperarousal in insomnia

Objective. To assess subjective and objective sleep characteristics and urinary metanephrine levels in patients with insomnia. Design and methods. We included patients with insomnia complaints and those without sleep– related complaints (control group) 18–75 years old. Subjective evaluation of the main sleep characteristics during the last month was assessed by the Pittsburgh Sleep Quality questionnaire, daytime sleepiness — by the Epworth Sleepiness Scale. For objective sleep evaluation we performed one-night polysomnography (PSG). Within 1 week after the PSG, daily urine was collected to determine the level of metaepinephrine. Results. The groups did not differ by age, mean sleep duration over the past month, number of night awakenings by the Pittsburgh Questionnaire, and level of daytime sleepiness. Sleep latency in insomnia group was 15 minutes longer than in the control group. PSG showed higher apnea-hypopnea and desaturation indices in the control group. There were no differences in daily urinary metanephrine excretion in the main and control groups. Correlation analysis showed no significant association between the metanephrine levels and the severity of somnolence and the index of periodic limb movements. Conclusions. Our analysis showed no significant differences in the daily urine metanephrine levels and the main PSG sleep characteristics among subjects with and without insomnia. Further work is required to clarify markers of insomnia and their negative health effects.

Chromogranin A in diagnosis of pheochromocytoma (comparative analysis)

To study the prognostic value of determining Chromogranin A blood level in the diagnosis of PHEO. We conducted a comparative analytical study of 157 patients with suspected PHEO, statistical analysis of 24-hour urinary metanephrine and normetanephrine excretion test was performed, as well as a blood test for CrA, in groups that included patients without PHEO, with primary tumor or its recurrence, confirmed according to MSCT and/or scintigraphy with MIBG and/or the clonidine suppression test. The parameters of efficiency of these methods were calculated by groups and it was noted that the lowest sensitivity of the CrA determination method was observed in the group with recurrence of PHEO (43.8%), their exclusion from the entire sample didnt change specificity of the method and it remained at a high level (85.45%), though sensitivity significantly increased up to 87.1%. Sensitivity of determining 24-hour urinary metanephrine excretion also increased significantly up to 96.8%, with 98.2% of specificity. The correlation between diameter of the tumor and its secretory activity was identified: small with CrA level (rho 0.491) and strong with total level of methylated catecholamines (rho 0.765). False positive results were more often observed in patients present with other neuroendocrine tumors (37.5%), as well as those taking proton-pump inhibitors (43.75%). The sensitivity and specificity of CrA determining method in the group of patients with methanephrins elevated within gray zone appeared to be 50 and 86.1%, respectively. A blood test for CrA can be recommended as a confirmatory test for diagnosing PHEO in cases of questionable methylated catecholamines indicators or in cases of suspected relapse of PHEO. The use of the test as a first-line method is only possible if there is no possibility to study methylated catecholamines. When interpreting CrA level, it is necessary to take into account the conditions that may cause false-positive results.

Surgical strategy for an adult patient with a catecholamine-producing ganglioneuroblastoma and a cerebral aneurysm: a case report

BackgroundGanglioneuroblastomas, particularly those that produce catecholamine, are extremely rare in adults. Here, we report an interesting surgical case of an adult patient with a catecholamine-producing ganglioneuroblastomas in her adrenal gland, suspected to be a pheochromocytoma, and with a cerebral aneurysm.Case presentationThe patient was a 73-year-old woman under treatment for hypertension. During a health check-up, a cystic retroperitoneal tumor was incidentally found in the superior pole of her right kidney. Her blood adrenaline level was slightly elevated, and her urinary adrenaline, noradrenaline, and dopamine levels were above the upper reference limits. In addition, 24-h urinary excretion of metanephrine, normetanephrine, and vanillylmandelic acid were all increased. 123I-Meta-iodobenzylguanidine scintigraphy showed an abnormal accumulation of the marker in the cyst wall. She was, therefore, diagnosed with a pheochromocytoma and scheduled for tumor resection. However, preoperatively, 8-mm-diameter cerebral aneurysm was incidentally found in her basilar artery. This required careful preoperative discussion. The aneurysm was difficult to approach and treat, and based on its position, shape, and size, the risk of rupture was low. Because hypertension is a major risk factor for aneurysmal rupture, we decided to proceed with the tumor resection. A lumbar catheter was placed to monitor the cerebral aneurysm for intraoperative rupture, and her transcranial motor-evoked potential and somatosensory-evoked potentials were monitored to track her intraoperative neurological function. During surgery, we carefully monitored fluctuations in blood pressure and resected the tumor with minimal mobilization. Postoperatively, head computed tomography confirmed that there was no sign of rupture. Histopathologically, the tumor was diagnosed as a catecholamine-producing ganglioneuroblastoma. The postoperative course was good, and the patient’s blood pressure improved.ConclusionsCareful perioperative management is needed for a patient with both a catecholamine-producing tumor and cerebral aneurysm.

Effects of a combined dietary, exercise and behavioral intervention and sympathetic system on body weight maintenance after intended weight loss: Results of a randomized controlled trial

BackgroundLifestyle based weight loss interventions are hampered by long-term inefficacy. Prediction of individuals successfully reducing body weight would be highly desirable. Although sympathetic activity is known to contribute to energy homeostasis, its predictive role in body weight maintenance has not yet been addressed. ObjectivesWe investigated, whether weight regain could be modified by a weight maintenance intervention and analyzed the predictive role of weight loss-induced changes of the sympathetic system on long-term weight regain. Design156 subjects (age > 18; BMI ≥ 27 kg/m2) participated in a 12-week weight reduction program. After weight loss (T0), 143 subjects (weight loss > 8%) were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until month 18 (T18). Weight regain at T18 (regainBMI) was the primary outcome. Evaluation of systemic and tissue specific estimates of sympathetic system was a pre-defined secondary outcome. ResultsBMI was reduced by 4.67 ± 1.47 kg/m2 during the initial weight loss period. BMI maintained low in subjects of the intervention group until T12 (+0.07 ± 2.98 kg/m2; p = 0.58 compared to T0), while control subjects regained +0.98 ± 1.93 kg/m2 (p < 0.001 compared to T0). The intervention group regained more weight than controls after ceasing the intervention (1.17 ± 1.34 vs. 0.57 ± 0.93 kg/m2) until T18. Consequently, BMI was not different at T18 (33.49 (32.64; 34.33) vs. 34.18 (33.61; 34.75) kg/m2; p=0.17). Weight loss-induced modification of urinary metanephrine excretion independently predicted regainBMI (R2 = 0.138; p < 0.05). The lifestyle intervention did not modify the course of urinary metanephrines after initial weight loss. ConclusionsOur lifestyle intervention successfully maintained body weight during the intervention period. However, no long-term effect could be observed beyond the intervention period. Predictive sympathetic activity was not persistently modified by the intervention, which may partially explain the lack of long-term success of such interventions.

Adipokiny, insulinorezistentnost' i aktivnost' simpato-adrenalovoy sistemy u yunoshey s ozhireniem, manifestirovavshim v pubertatnyy period

69 young men with obesity manifesting at puberty have been examined. The average age was 19,22±0,26. 17 healthy young men, whose average age was 22 ± 0,72 years old, constituted a control group. The examined were divided according to their blood pressure (BP): the first subgroup included 36 young men with normal blood pressure, the other subgroup included 33 young men with arterial hypertension. Levels of blood lipid spectrum, levels of leptin, resistin, adiponectin, insulin in serum, urinary metanephrine excretion were measured. We obtained the following results: young men with obesity identified atherogenic changes in lipid metabolism, insulin resistance and compensatory hyperinsulinemia. Regardless of the level of blood pressure they showed a significant increase in leptin levels. In the subgroup of patients with hypertension we found increased urinary excretion of metanephrine, indicating increased activity of the sympathoadrenal system and its involvement in the formation of hypertension. The level of adiponectin in the surveyed tended to decrease, more pronounced in the combination of obesity and hypertension.

Changes in Urinary Total Metanephrine Excretion in Recurrent and Malignant Pheochromocytomas and Secreting Paragangliomas

We quantified urinary excretion of total metanephrines (metanephrine plus normetanephrine) (UETM) in 261 patients with pheochromocytoma (PH) or secreting paraganglioma, before primary tumor resection. We then determined UETM 2 weeks after primary tumor resection and once per year thereafter. The tumor was considered benign in 242 patients and malignant in 19 patients. Patients with malignant tumors had higher UETM and tumor diameters, lower plasma epinephrine concentrations, and were more likely to have secreting paragangliomas than patients with benign tumors. In the 215 patients with a single-benign primary tumor, preoperative UETM and tumor diameter were significantly correlated. Thirty-six patients subsequently developed recurrences or new tumors, which were malignant in 18 cases. All recurrent or new tumors could be detected before the onset of symptoms, on the basis of an increase in metanephrine concentration. We followed one patient with von Hippel-Lindau disease and a new tumor for 50 months before reoperation and found that UETM and tumor diameter were significantly correlated. In patients with malignant tumors, the logarithm of UETM was significantly correlated with time, suggesting an exponential increase in tumor activity and, presumably, tumor burden. Urinary metanephrine excretion is a marker of tumor activity and a surrogate of tumor burden in patients with pheochromocytoma or secreting paraganglioma. UETM excretion could be used to assess treatment response in malignant cases.

Diabetes as a marker of pheochromocytoma in hypertensive patients

To assess the prevalence of diabetes in patients with pheochromocytoma and the probability of pheochromocytoma occurring in hypertensive patients with or without diabetes. A tertiary, referral hypertension department. We compared age, body mass index and the frequency of diabetes in 191 patients with pheochromocytoma and a random sample of 880 patients with essential hypertension. Diabetes was defined as current antihyperglycemic treatment or two fasting blood glucose concentrations >or= 7 mmol/l. For patients with pheochromocytoma, we also recorded plasma catecholamine concentrations, the urinary excretion of metanephrines, and tumor characteristics. Diabetes was present in 68 (35.6%) patients with pheochromocytoma and 192 (21.8%) patients with essential hypertension (P < 0.001). Pheochromocytoma patients with or without diabetes did not differ in body mass index, plasma noradrenaline concentration, metanephrine excretion or tumor characteristics. Age, duration of hypertension and plasma adrenaline concentration were significantly and independently associated with diabetes in patients with pheochromocytoma. They were younger, more likely to be female and had a lower body mass index than those with essential hypertension (P < 0.01). After adjustment for these three variables, the odds ratio for pheochromocytoma in hypertensive patients with diabetes was 5.5 (95% confidence interval, 3.5-8.7). For patients younger than the age of 51 years with a body mass index < 25 kg/m2, the odds ratio was 18.9 (95% confidence interval, 5.9-58.8). Diabetes is present in one in three patients with pheochromocytoma. In young patients with hypertension and normal body weight, the presence of diabetes is a clinical clue to the diagnosis of pheochromocytoma.

Effects of slow-release octreotide in patients with malignant or recurrent pheochromocytoma

To investigate the clinical and hormonal effects of a slow-release formulation of the somatostatin analogue, octreotide, in patients with malignant or recurrent pheochromocytoma. In a prospective study, 10 patients underwent 111Indium labelled octreotide scintigraphy and then received three monthly intramuscular 20 mg octreotide injections. Patients were evaluated before the first injection and 30 days after the third injection (D84). The assessed parameters were: symptoms, blood pressure (BP), plasma noradrenaline (NA) concentrations, blood glycosylated hemoglobin (HbA1c), insulinemia, and the levels of two putative markers of tumor burden, urinary metanephrine/creatinine (MN/Cr) and plasma chromogranine A (CGA) concentration. There were no statistically or clinically significant variations in BP levels, MN/Cr excretion ratio, plasma CGA, plasma NA and, or symptoms. Long-acting octreotide was well tolerated but a significant increase in HbA1c was observed (p=0.03). Patients with (n=6) or without (n=4) 111Indium octreotide uptake did not differ in urinary metanephrine excretion, plasma NA, HbA1c, plasma CGA, symptom evolution, and BP,. Patients showing tracer uptake had a larger reduction in plasma insulin that those without (-1.0 mUI/L vs +2.3 mUI/L; p=0.03). Our data suggest that slow-release octreotide is not useful for the long term treatment of patients with malignant or recurrent pheochromocytoma. (See Table)

Effects of slow-release octreotide on urinary metanephrine excretion and plasma chromogranin A and catecholamine levels in patients with malignant or recurrent phaeochromocytoma.

Somatostatin receptors are present on human phaeochromocytomas. Catecholamine concentrations may decrease following short-term administration of somatostatin agonists to patients with phaeochromocytomas. We carried out a prospective study on 10 patients with malignant or recurrent phaeochromocytomas to examine the clinical and hormonal effects of three monthly intramuscular injections of 20 mg slow-release octreotide. Patients underwent somatostatin receptor scintigraphy using 111In-pentetreotide before slow-release octreotide was administered. The patients' symptoms, blood pressure, blood glucose concentrations, glycosylated haemoglobin concentra-tions, plasma insulin and noradrenaline concentrations, and the levels of two putative markers of tumour burden, urinary metanephrine excretion and plasma chromogranin A concentration, were recorded before the first injection and 28 days after the third injection. Slow-release octreotide did not significantly alter symptoms, blood pressure, blood glucose concentrations, plasma catecholamine and chromogranin A concentrations or metanephrine excretion. Median glycosylated haemoglobin concentrations increased from 5.3% to 6.0% (P = 0.03). Patients whose tumours took up 111In- pentetreotide did not differ from those whose tumours did not after slow-release octreotide treatment in terms of symptoms, blood pressure, blood glucose, plasma catecholamine and chromogranin A concentrations or metanephrine excretion. Our data suggest that slow-release octreotide is of limited value for the long-term treatment of patients with malignant or recurrent benign phaeochromocytomas.

Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center.

To identify preoperative factors associated with 30-day morbidity and mortality after pheochromocytoma surgery, we carried out an external review of the records of all patients undergoing pheochromocytoma surgery from 1975 to 1997 at a single center. One hundred and forty-seven patients, including 23 with malignant tumors at the time of the first operation, underwent 165 operations. Death, resection of a neighboring organ, further surgery, secondary transfer to an intensive care unit, and any events associated with a surgical stay exceeding 10 days were defined as complications. Mortality and morbidity were 4 of 165 (2.4%) and 38 of 161 (23.6%), respectively. Morbidity included 13 spleen resections and hematomas. Spleen complications were not related to tumor location, but were probably due to the operative strategy used, a transperitoneal complete abdominal exploration including both adrenal glands. Complications were independently associated with preoperative systolic blood pressure [odds ratio (OR), 1.14/cm Hg], urinary metanephrine excretion (OR, 1.18/10 micromol x day), and with the number of operations (repeat vs. first operation OR, 5.36). In conclusion, pheochromocytoma resection consistently involves a risk of complications. Spleen damage should be prevented by complete preoperative localization studies and an elective or laparoscopic surgical approach. Careful blood pressure control should help prevent complications. Patients with high secretion tumors and those undergoing repeat intervention are at high risk of complications and should be referred to centers familiar with pheochromocytoma management.

Progrès récents dans le diagnostic, l’évaluation pronostique et le traitement des phéochromocytomes

Introduction. – Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. Current knowledge and key points. – The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. Future prospects and projects. – Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect.

Adrenal Incidentaloma

Pheochromocytomas are rare tumors, and patients usually present with paroxysmal symptoms. However, because of the advances in and frequent use of computerized imaging, adrenal pheochromocytomas may be discovered incidentally in patients who lack typical signs and symptoms. To determine the prevalence of adrenal incidentaloma as the initial finding in patients with benign sporadic adrenal pheochromocytoma, we retrospectively reviewed the clinical findings of 150 patients with benign sporadic adrenal pheochromocytoma diagnosed at the Mayo Clinic, Rochester, Minnesota, from 1978 to 1995. Although the majority of patients had symptoms attributable to catecholamine excess, 15 (10%) presented with an adrenal mass lesion discovered serendipitously on radiologic examination in the absence of paroxysmal symptoms. Two of these patients were normotensive, and urinary excretion of metanephrines and catecholamines was normal in one. The other 13 patients presented with sustained hypertension and/or one of its complications as the sole manifestation of catecholamine excess, an excess confirmed by biochemical urinary studies. Adrenal incidentaloma represents part of the spectrum of presentation of benign sporadic adrenal pheochromocytoma, a presentation found in 10% of patients.

Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity.

To assess the mechanisms related to tetanus-induced acute renal failure (ARF), 30 patients with tetanus had their renal function prospectively studied and factors possibly related to renal changes were evaluated during four weeks of hospitalization. Fifty percent of these patients had a glomerular filtration rate (GFR) < or = 50 ml/min in the first or second week of hospitalization (Group I) and 50% had a GFR > 50 ml/min throughout the entire hospitalization period (Group II). Age, gender, tetanus incubation time and tetanus onset time, hospitalization time, use of nephrotoxic drugs, need for mechanical ventilation with intermittent positive pressure, and presence of systemic infection were similar in both groups. None of the patients presented with oliguria. Autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, by increased heart rate and elevated urinary metanephrine excretion, was higher in Group I compared with Group II. Plasma renin activity, serum creatinephosphokinase levels, and myoglobinuria were not significantly different between the two groups. These results strongly suggest that tetanus-induced ARF has a high prevalence, is characterized by early onset, and is probably related to ANS overactivity.

Prevention of cardiac hypertrophy by a sub-antihypertensive dose of the alpha 1-adrenergic antagonist bunazosin in Dahl salt-sensitive rats.

To assess the protective effect of an alpha 1-blocker on the development of cardiac hypertrophy, the selective alpha 1-receptor antagonist bunazosin (2 mg/kg/d, by oral gavage and in drinking water) was given to male Dahl salt-sensitive rats fed a 4% NaCl diet for 7 weeks. Control animals received water only by the same method. Treatment with bunazosin was started when the animals were 7 weeks of age. Blood pressure, pulse rates, and body weight were measured every week during the experiment. Urine was collected for 24 h on the final day of the experiment. All animals were killed by decapitation, blood was collected, and the heart was removed. In both the treated and control groups, time-dependent increase in blood pressure and body weight were observed, and there were no significant differences between the groups in blood pressure or body weight during the experiment. Pulse rate remained unchanged in both groups throughout the experiment. The left ventricular weight/body weight ratio and the left ventricular tissue DNA content were significantly lower in the rats receiving bunazosin than in the control rats. Plasma renin activity, plasma aldosterone, and plasma atrial natriuretic peptide did not differ significantly between the two groups. No significant differences in glomerular filtration rate, urine volume, sodium excretion, urinary metanephrine excretion, and urinary normetanephrine excretion were noted between the two groups. The results indicate that a sub-antihypertensive dose of bunazosin can inhibit the development of cardiac hypertrophy without suppression of the pressure load, suggesting an important role of alpha 1-adrenergic receptors in the pathogenesis of cardiac hypertrophy following the development of hypertension.

Plasma Metanephrines in the Diagnosis of Pheochromocytoma

To examine whether tests for plasma metanephrines, the o-methylated metabolites of catecholamines, offer advantages for diagnosis of a pheochromocytoma over standard tests for plasma catecholamines or urinary metanephrines.Cross-sectional study.3 clinical specialist centers.52 patients with a pheochromocytoma; 67 normotensive persons and 51 patients with essential hypertension who provided reference values; and 23 patients with secondary hypertension and 50 patients with either heart failure or angina pectoris who served as comparison groups.Plasma concentrations of catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrine and metanephrine) were measured in all patients. The 24-hour urinary excretion of metanephrines was measured in 46 patients with pheochromocytoma.Pheochromocytomas were associated with increases in plasma concentrations of metanephrines that were greater and more consistent than those in plasma catecholamine concentrations. No patient with a pheochromocytoma had normal plasma concentrations of both normetanephrine and metanephrine. The sensitivity of these tests was 100% (52 of 52 patients [95% CI, 94% to 100%]), and the negative predictive value of normal plasma concentrations of metanephrines was 100% (162 of 162 patients). Tests for plasma catecholamines yielded eight false-negative results and a sensitivity of 85% (44 of 52 patients [CI, 72% to 93%]). The negative predictive value of normal plasma concentrations of catecholamines was 95% (156 of 164 patients). Tests for urinary metanephrines yielded five false-negative results and a sensitivity of 89% (41 of 46 patients [CI, 76% to 96%]). Because no statistical difference was noted in the number of false-positive results between tests for plasma metanephrines (15%) and tests for plasma catecholamines (18%), the specificities of the two tests did not differ.Normal plasma concentrations of metanephrines exclude the diagnosis of pheochromocytoma, whereas normal plasma concentrations of catecholamines and normal urinary excretion of metanephrines do not. Tests for plasma metanephrines are more sensitive than tests for plasma catecholamines or urinary metanephrines for the diagnosis of pheochromocytoma.

Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications

Twelve patients with severe obstructive sleep apnoea were included in an open, long-term, prospective, follow-up study addressing the effects of nasal continuous positive airway pressure (CPAP) on sympathetic activity, cardiac structure and blood pressure. Plasma norepinephrine (P-NE) (daytime at rest), daytime and night-time urinary excretion of NE (U-NE), vanylmandelic acid and metanephrines, together with 24 h noninvasive blood pressure (BP) recording and Doppler-echocardiography, were assessed before and after a mean of 20.5 (range 14-26) months of CPAP. Average self-reported use of CPAP was 89% (range 65-100%) of time spent in bed. Resting daytime P-NE ranged 0.35-0.83 ng.ml-1, which is elevated compared to healthy controls. Only night-time U-NE, mean daytime BP and average 24 h BP were related to severity of OSA. Night-time metanephrine was related to daytime and night-time diastolic, as well as night-time systolic, BP. Left ventricular mass index (LVMI) at baseline was correlated to daytime systolic BP and P-NE. Long-term CPAP treatment reduced biochemical markers of sympathetic activity. P-NE decreased by approximately 50%, and daytime and night-time vanylmandelic acid and metanephrine by 32-54%. In contrast, there were no overall reductions in BP or LVMI. It is concluded that obstructive sleep apnoea is associated with high sympathetic activity both during sleep and waking periods. Urinary metanephrine excretion seemed to reflect blood pressure, but neither daytime nor night-time catecholamine excretion was directly related to disease severity in patients with severe obstructive sleep apnoea.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary Catecholamine Excretion in Sexually Abused Girls

The objective of this study was to examine urinary catecholamine excretion in a self-selected sample of sexually abused and demographically matched control girls recruited from a prospective, longitudinal study. Twenty-four--hour urinary catecholamine and metabolite concentrations of epinephrine, norepinephrine, dopamine, 3-methoxy-4-hydroxyphenylglycol, metanephrine, normetanephrine, vanillylmandelic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in 12 sexually abused and 9 control girls, aged 8 to 15 years. Psychiatric profiles also were obtained. The abused subjects excreted significantly greater amounts of metanephrine, vanillylmandelic acid, homovanillic acid, and total catecholamine synthesis as measured by the sum of epinephrine, norepinephrine, dopamine, and their metabolites compared to values from control subjects. When the means of all significant biochemical measures were adjusted by the covariate effect of height, only homovanillic acid and group interaction remained significant. There were positive trends toward significantly higher urinary excretion of metanephrine, vanillylmandelic acid, and total catecholamine synthesis. Sexually abused girls also had a greater incidence of suicidal ideation, suicide attempts, and dysthymia than control girls. These findings support the idea that sexually abused girls show evidence of higher catecholamine functional activity compared with controls. The clinical significance of these findings in their similarity to the psychobiology of both post-traumatic stress disorder and major depressive disorder. Results from this pilot study may be of value in understanding the mechanisms of depressive and anxiety disorders and in the clinical treatment of maltreated children.