CSF monoamine metabolites in chronic pain

Metabolites of selected neurotransmitters (5-HIAA, HVA and DOPAC) and beta-endorphin were measured in the CSF of 39 chronic pain patients and compared to controls. Twelve of the pain patients also fulfilled criteria for major depression. The concentration of 5-HIAA was increased in female but not male pain patients; there was no significant difference in the CSF concentrations of HVA and DOPAC. The presence of depression did not influence the concentrations of neurotransmitters. No correlation was found between the concentrations of monoamine metabolites and beta-endorphin. However, there was a positive correlation between 5-HIAA and HVA in controls and chronic pain patients without depression but not in depressed patients. It is concluded: chronic pain states are associated with elevation of CSF 5-HIAA in female patients; depression abolishes a positive correlation between 5-HIAA and HVA.     

Daily cyclic changes in the urinary excretion of 5-hydroxyindoleacetic acid in patients with carcinoid tumors

BACKGROUND: Vasoactive peptides produced by neuroendocrine tumors can induce characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and wheezing). To what extent external factors provoke these symptoms and how excretion of 5-hydroxyindoleacetic acid (5-HIAA), the degradation product of serotonin, varies throughout the day remain unknown. In this study, we investigated whether symptoms and daily activity are related to 5-HIAA excretion and whether 24-h urine collection is needed. METHODS: In 26 patients with metastatic carcinoid (14 men and 12 women; median age, 60 years) urine was collected in portions of 4 or 8 h during 2 days. Patients were asked to keep a diary in which they noted symptoms of flushes, consistency of stools, activities, and food intake. RESULTS: Excretion of 5-HIAA in 24-h urine was increased in 88% of the patients (median, 515 micromol/24 h). Overnight-collected urine appeared the most representative for 24-h collection concentrations (correlation coefficient = 0.81). We found no clear correlation between symptoms of the carcinoid syndrome and degree of activity. Watery diarrhea was reported only by patients with strong variations in 5-HIAA excretion. One-half of the patients (n = 16) exhibited a high variability in urinary 5-HIAA excretion throughout the day, with increased concentrations most prominent in morning collections (P = 0.0074) and lower concentrations in the evening (P = 0.0034). In the other patients these curves were flat. CONCLUSIONS: Cyclic changes in patients relate to high variability in 5-HIAA excretion. Overnight-collected urine can replace the 24-h urine collection, and marked variations in 5-HIAA excretion seem to be associated with severity of diarrhea.     

Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.     

The role of serotonin as a mediator of emesis induced by different stimuli

The aim of this work was to evaluate the impact of changes in serotonin metabolism on the pathophysiology of different types of emesis: pregnancy-induced emesis, emesis associated with inner-ear dysfunction, and cisplatin-induced emesis. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, was measured in 13 women with pregnancy-induced emesis, 12 patients who had nausea and vomiting following inner-ear dysfunctions, 27 patients with cisplatin-induced emesis and a control group of 21 women. 5-HIAA was measured with a fluorescence polarization immunoassay (Abbott) and corrected for varying urine concentrations. Both patients with emesis associated with inner-ear dysfunction and patients with pregnancy-associated emesis showed a similar 5-HIAA excretion pattern compared with the control group. No correlation between intensity of nausea or vomiting and changes in 5-HIAA excretion could be detected. In patients receiving cisplatin, the 5-HIAA excretion increased rapidly within the 12 h following cisplatin administration and returned to baseline levels after 24 h. There was a parallel increase of 5-HIAA excretion and numbers of emetic episodes in the first 12 h, but delayed emesis was not associated with elevated 5-HIAA excretion. Our results provide evidence that serotonin is involved in the pathophysiology of cisplatin-induced acute emesis. Cisplatin-induced delayed emesis, pregnancy-associated emesis, and emesis due to inner-ear dysfunction are not associated with elevated levels of 5-HIAA excretion. The serotonin pathway probably represents only one of many different afferent mechanisms capable of initiating the emesis cascade.     

Cerebrospinal fluid monoamine metabolites and neuropeptides in patients with panic disorder.

Concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as somatostatin (SRIF) and beta-endorphin (beta-END) were assayed in the cerebrospinal fluid (CSF) of 34 patients with panic disorder and of ten neurological controls. No aberrations of the monoaminergic or peptidergic variables measured were found in the nonpanic state of patients with panic disorder. A modest correlation (P = 0.04) between total anxiety scores and CSF MHPG was observed.     

A comparison of dopamine and homovanillic acid excretion, as prognostic indicators in malignant phaeochromocytoma

The urinary excretion of dopamine and its metabolite homovanillic acid (HVA) were compared in 15 patients with malignant phaeochromocytoma. Six patients with increased dopamine and HVA excretion had disseminated malignancy and the poorest prognosis. Four patients with increased urinary dopamine levels but normal HVA excretion also had widespread metastases and poor prognosis. The best prognosis was for 5 patients who had normal excretion of dopamine and HVA, and minimal disease. When dopamine and HVA excretion were considered separately, it was found that duration of survival was significantly better for patients with normal dopamine excretion than those with increased dopamine excretion (p less than 0.003). There was no significant difference in survival time between patients with normal and increased HVA excretion. In this study dopamine excretion appeared to be a more discriminating biochemical index of malignancy, prognosis and disease progression than HVA excretion.     

Cerebrospinal Fluid Monoamine Metabolites and Neuropeptides in Patients with Panic Disorder

Concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG) as well as somatostatin (SRIF) and ß-endorphin (ß-END) were assayed in the cerebrospinal fluid (CSF) of 34 patients with panic disorder and of ten neurological controls. No aberrations of the monoaminergic or peptidergic variables measured were found in the nonpanic state of patients with panic disorder. A modest correlation (P = 0.04) between total anxiety scores and CSF MHPG was observed.     

Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine.

The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.     

Insulin metabolism is altered in migraineurs: a new pathogenic mechanism for migraine?

BACKGROUND: Migraine is a complex biochemical dysfunction attributed to a disorder of the trigeminal and hypothalamic pathways. Impairment of glucose metabolism has been reported in migraine, but data are scanty and inconsistent. OBJECTIVE: The main aim was to verify whether migraineurs have abnormalities of the glucose and insulin metabolism.We also studied correlations between blood glucose and insulin and between insulin levels and migraine severity. PATIENTS AND METHODS: Patients with migraine or headache other than migraine, and healthy volunteers were included. All had general blood tests and a standard oral glucose tolerance test after a 12-hour fast, and glucose and insulin were measured. RESULTS: Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men), 25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls (24 women, 2 men). Multivariate analysis confirmed a significant difference between groups for glucose levels (P < .0001), but no significant time interaction. The differences were mostly between migraine and healthy controls (P < .0001) and to a lesser extent between other headaches and healthy controls (P < .05). A significant difference between groups was also found for insulin (P < .0001), with a significant time interaction. The difference was confirmed for migraine compared to other headaches (P < .0001) and healthy controls (P < .0001). CONCLUSIONS: Blood glucose levels may be high in headache patients, but do not seem to be specific to migraineurs. Insulin levels were higher in migraineurs, and seemed specific to this group. These findings are in keeping with recent reports on the effects of insulin on brain functions and lend support to the possibility that insulin is involved in the pathogenesis of migraine.     

Diclofenac increases beta-endorphin plasma concentrations

Plasma and ventricular cerebro-spinal fluid (CSF) Beta-endorphin concentrations were evaluated after chromatographic separation in patients carrying a ventricular shunt before and after the administration of diclofenac or placebo. In the same subjects the ventricular CSF concentrations of the serotonin and the catecholamine metabolites 5-hydroxyindole-acetic acid (5-HIAA), homovanillic acid (HVA) and MOPEG were also evaluated. Plasma, but not ventricular, Beta-endorphin concentrations increased significantly after diclofenac, while placebo was ineffective. No significant changes in ventricular 5-HIAA, HVA or MOPEG levels were observed. These data suggest a role for Beta-endorphin in the analgesic effect of diclofenac.     

高效液相色谱法快速检测单胺类神经递质及其代谢产物

背景:单胺类神经递质及其代谢产物对实验研究帕金森病和实验诊断嗜铬细胞瘤具有重要意义,是当今的研究热点。目的:建立高效液相色谱法同时快速测定肾上腺素、去甲肾上腺素、多巴胺、5-羟色胺、5-羟吲哚乙酸、高香草酸及多巴柯7种单胺类神经递质及其代谢产物。设计:病例-对照观察和随机对照动物实验。单位:青岛大学医学院附属医院检验科及青岛大学医学院附属医院海阳分院。对象:实验于2003-10/12在青岛大学医学院生理教研室和青岛大学医学院附属医院检验科完成。①2例嗜铬细胞瘤患者,均经CT,MRI或病理切片和临床证实为该病。12例正常对照均为在校大学生,且经查排除高血压、内分泌系统疾病和其他疾病。②选用健康雌性Wistar大白鼠12只,体质量150～180g。随机数字表法分为2组,正常对照组和帕金森病组,每组大鼠各6只。方法:制备7种物质样品(肾上腺素、去甲肾上腺素、多巴胺、5-羟色胺、5-羟吲哚乙酸、高香草酸及多巴柯)的标准色谱图,同时进行样品精密度和回收率的检测。采用高效液相色谱法检测12例正常对照和2例嗜铬细胞瘤患者24h尿中的儿茶酚胺类物质。同时以6-羟基多巴胺损毁帕金森病组大鼠大脑一侧前脑束,以监测正常和帕金森病大鼠健侧及损毁侧尾壳核区纹状体内单胺类神经递质及其代谢产物的释放特点。主要观察指标:①样品精密度和回收率检测结果。②12例正常对照和2例嗜铬细胞瘤患者24h尿中儿茶酚胺类物质的测定结果。③各组大鼠纹状体内单胺类神经递质及其代谢产物的释放特点。结果:12例正常对照和2例嗜铬细胞瘤患者均获得24h尿中儿茶酚胺类物质检测结果,并进入结果分析。实验动物在实验中无死亡。①高效液相色谱法对肾上腺素、去甲肾上腺素、多巴胺、5-羟色胺、5-羟吲哚乙酸、高香草酸及多巴柯7种单胺类物质的线性范围为2～1000μg/L,最低检测限为2～30μg/L,批内精密度为3.0%～8.6%,批间精密度为3.8%～9.7%。多巴胺的平均回收率为107.3%、去甲肾上腺素为89.4%、肾上腺素为80.1%,其余4种物质为89.2%～95.7%。②2例嗜铬细胞瘤患者24h尿中儿茶酚胺类物质的含量显著高于正常人,其中1例以肾上腺素明显增高为主,另1例以去甲肾上腺素明显增高为主,均高于正常人10倍左右。③帕金森病大鼠健侧尾壳核内多巴胺及其代谢产物多巴柯、高香草酸含量均在正常范围内,损毁侧尾壳核内多巴胺、5-羟色胺、多巴柯及高香草酸均显著降低,差异有显著性意义(P<0.01);5-羟色胺及其代谢产物5-羟吲哚乙酸含量无明显改变。④帕金森病大鼠健侧尾壳核内多巴胺更新率(多巴柯/多巴胺和高香草酸/多巴胺的比值)升高;损毁侧尾壳核内多巴胺更新速度也加快,与正常对照组比较差异均有显著性意义(P<0.05)。结论:高效液相色谱法能满足对大白鼠帕金森病模型的研究和对嗜铬细胞瘤患者实验诊断的需要。     

Neurotransmission and the experience of low back pain; no association between CSF monoamine metabolites and pain

We have investigated the possible associations between the demographic, clinical and psychological characteristics of 80 patients with low back pain and the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal central nervous system metabolites of serotonin, dopamine and noradrenaline, and of tryptophan, the amino acid precursor of serotonin. Neither the clinical measures nor the psychological characteristics were significantly correlated with the CSF neurochemistry. Therefore the hypothesis about an intimate relationship between monoaminergic neurotransmission and the experience of chronic low back pain was not confirmed. Among the other factors studied, body height contributed most to the variance in both 5-HIAA and HVA concentrations; the levels of MHPG increased with age.     

Increased prevalence of migraine in patients with uninvestigated dyspepsia referred for open-access upper gastrointestinal endoscopy

BACKGROUND AND STUDY AIMS: The association between gastrointestinal symptoms and headache is frequently unrecognized. The aim of the present study was to determine the prevalence of migraine in dyspeptic outpatients referred for upper gastrointestinal endoscopy. PATIENTS AND METHODS: Patients aged 18 - 55 years undergoing upper gastrointestinal endoscopy for dyspeptic symptoms in three endoscopic units were recruited consecutively. All of the patients were given a validated questionnaire on headache symptoms in order to determine the prevalence of migraine. Patients were divided into four groups (ulcer-like dyspepsia, reflux-like dyspepsia, dysmotility-like dyspepsia, only nausea and/or vomiting). Age-matched blood donors were given the same questionnaires and served as controls. RESULTS: A total of 378 patients (mean age 40 +/- 11, 52 % men) and 310 controls (mean age 39 +/- 11, 56 % men) were enrolled. No differences were observed between the two groups in the prevalence of migraine (15 % vs. 11 %; P = 0.12). A higher prevalence of migraine was found among women in both groups (P < 0.006). In patients with reflux-like and ulcer-like dyspepsia, the prevalence of migraine did not differ from that in the control individuals (8 % and 7 %, respectively), whereas a higher prevalence of migraine was noted in patients with dysmotility-like dyspepsia (23 %; P < 0.02 vs. controls, those with ulcer-like dyspepsia and those with reflux-like dyspepsia) and in patients with nausea and/or vomiting alone (53 %; P < 0.002 vs. all other groups). The multivariate analysis confirmed that the symptom pattern and sex were the only variables independently associated with migraine. CONCLUSIONS: A diagnosis of migraine should be considered in young patients referred for upper gastrointestinal endoscopy due to nausea and/or vomiting or for dysmotility-like dyspepsia.     

Study on monoamine metabolite contents of cerebrospinal fluid in patients with neurodegenerative diseases

Main monoamine metabolities of cerebrospinal fluid (CSF), i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), were measured in 74 patients with neurodegenerative diseases, in 30 normal control subjects and in 16 diseased control subjects without neurodegenerative diseases. The symptoms of patients were scored according to an original scale. It was suggested by statistical study including multiple regression analysis that there might be significant relationship between CSF-MHPG level and extrapyramidal symptoms, or autonomic symptoms, and between CSF-5-HIAA level and extrapyramidal, or cerebellar symptoms, and between CSF-HVA level and extrapyramidal, pyramidal, or cerebellar symptoms. It was also suggested that the severer the symptoms of patients with Parkinson's disease, Shy-Drager syndrome, or olivopontocerebellar atrophy became, the lower the levels of monoamine metabolities of CSF became. The activity of peripheral catecholamine metabolism might influence the CSF-MHPG level because of the significant positive correlations between CSF-MHPG level and urine noradrenaline or vanillylmandellic acid level. The level of MHPG was high in patients with severe amyotrophic lateral sclerosis or hereditary spinocerebellar degeneration possibly because of stress with respiratory dysfunction.     

Serotonin: Change in Plasma-free Level and Urinary Excretion after LM 5008 and Reserpine

SYNOPSIS
LM 5008, a potent 5-HT uptake inhibitor, induced an increase in plasma-free 5-HT level in a higher proportion than its metabolite 5-HIAA. In contrast, reserpine provoked a greater rise in 5-HIAA than in 5-HT, indicating stimulation of 5-HT turnover. LM 5008 potentiated the effects of reserpine on bound and free 5-HT and 5-HIAA levels but potentiated more the plasma-free 5-HT (4 times) than 5-HIAA (2.5 times), over reserpine-induced increases. Moreover, the rise in urinary excretion of 5-HT induced by reserpine was potentiated by LM 5008, whereas 5-HIAA was decreased. The differences between these two drugs implies that they do not act on the same platelet site. Since migraine has been proposed as a "low 5-HT syndrome," LM 5008 may be useful as an anti-migrainous agent.     

与良性阵发性位置性眩晕相关的影响因素分析

目的 探讨良性阵发性位置性眩晕(BPPV)相关的影响因素.方法 选取2018年9月至2020年9月于该院神经内科就诊的BPPV患者126例作为BPPV组,选取同期年龄、性别相匹配的70例体检健康者作为对照组.记录两组人群的性别、年龄、饮酒史、吸烟史、糖尿病、高血压、家族冠心病史、偏头痛病史.检测白细胞计数(WBC)、血...     

Behavioral studies with anxiolytic drugs. V. Behavioral and in vivo neurochemical analyses in pigeons of drugs that increase punished responding

Behavioral and neurochemical effects of several drugs that increase punished responding were studied in pigeons. Key pecking was established under a schedule of reinforcement in which periods of food-maintained responding alternated with periods in which behavior also was suppressed by the presentation of electric shock. Buspirone (0.1-10.0 mg/kg), gepirone (0.1-1.0 mg/kg), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1-3.0 mg/kg), chlordiazepoxide (3.0-30.0 mg/kg) and to a lesser extent clozapine (0.1-1.0 mg/kg) all produced increases in punished responding at doses having little effect on or decreasing the rate of unpunished responding. Neurochemical analyses on samples of cerebrospinal fluid after administration of several doses of each compound were performed for the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), the noradrenergic metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). Gepirone, 8-OH-DPAT and the novel anxiolytic buspirone produced decreases in 5-HIAA at doses that increased punished responding in the behavioral studies. Buspirone increased levels of HVA and DOPAC, whereas its structural analog gepirone and the 5-hydroxytryptamine1A agonist 8-OH-DPAT had little effect on or decreased levels of these metabolites. Chlordiazepoxide, a prototypic benzodiazepine anxiolytic, produced only modest decreases in each of the metabolites studied. Clozapine, an atypical antipsychotic drug, produced increases in each of the metabolites studied, although only the 5-HIAA effect occurred at doses that were not behaviorally disruptive. Haloperidol (0.03-1.0 mg/kg) produced only decreases in punished and unpunished responding, whereas eliciting increases in the appearance of MHPG, DOPAC and HVA; levels of 5-HIAA were relatively unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between parameters of serotonin metabolism and emetogenic potential of platinum-based chemotherapy regimens

 Evaluation of the relationship between parameters of serotonin (5-HT) metabolism and emesis in platinum-based chemotherapy. Female patients receiving chemotherapies containing either cisplatin (35 patients; 80 courses) or carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Comparisons were performed for single-agent cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose DDP (≥75 mg/m²) versus high-dose DDP combined with cyclophosphamide, high-dose versus low-dose DDP (≤50 mg/m²), and single-agent CBDCA versus a combination with alkylating agents. Cisplatin induced both a significantly higher frequency of emesis and a significantly higher increase of 5-HIAA excretion than carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on day 1. No significant difference was found when single-agent cisplatin was compared with cisplatin combined with cyclophosphamide. In contrast, a combination of carboplatin with alkylating agents induced a larger increase in urinary 5-HIAA and showed a higher emetogenic potential than single-agent carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide evidence for a relationship between emetogenic potential and patterns of 5-HIAA excretion following platinum-based chemotherapy.     

Proteinuria in newly diagnosed type II diabetic patients

Urinary excretion of albumin, IgG, and beta 2-microglobulin was examined in 132 (69 men, 63 women) newly diagnosed, middle-aged type II diabetic patients and in 144 (62 men, 82 women) nondiabetic control subjects. Both male (N = 57) and female (N = 29) diabetic patients with normal urinary sediment showed an increased excretion of albumin compared with the respective nondiabetic subjects, and male diabetic patients also had an increased IgG excretion. No consistent difference was found in urinary beta 2-microglobulin concentration between the diabetic and nondiabetic subjects. In all, 19.5% of the diabetic subjects with normal urinary sediment (12 men, 5 women) showed urinary albumin concentration exceeding the highest value (35 mg/24 h) found in nondiabetic subjects without renal disease. The urinary excretion of albumin in the diabetic subjects was not associated with the presence of hypertension or coronary heart disease or with the fasting blood glucose or serum insulin levels measured at diagnosis of diabetes. In male diabetic subjects with urinary albumin excretion greater than 35 mg/24 h, a reduced creatinine clearance was found, suggesting the presence of structural damage associated with diabetic nephropathy. The early increase of urinary albumin excretion in type II diabetic patients may be mostly functional in nature. However, some patients may have structural renal damage associated with diabetic nephropathy present at diagnosis.     

Automated on-line solid-phase extraction coupled with HPLC for measurement of 5-hydroxyindole-3-acetic acid in urine

BACKGROUND: Quantification of 5-hydroxyindole-3-acetic acid (5-HIAA) in urine is useful in diagnosing and monitoring of patients with carcinoid tumors and in the study of serotonin (5-hydroxytryptamine) metabolism in various disorders. We describe an automated method that incorporates on-line solid-phase extraction (SPE) and HPLC to measure urinary 5-HIAA. METHODS: Automated prepurification of urine was accomplished with HySphere-resin GP SPE cartridges containing strong hydrophobic polystyrene resin. The analyte (5-HIAA) and internal standard [5-hydroxyindole-3-carboxylic acid (5-HICA)] were eluted from the SPE cartridge, separated by reversed-phase HPLC, and detected fluorometrically with a total cycle time of 20 min. Urinary excretion of 5-HIAA was measured in a group of patients with known and suspected carcinoid tumors (n=63) and in 20 patients with autism. RESULTS: The internal standard (5-HICA) and 5-HIAA were recovered in high yields (87.2%-114%). Within- and between-series CVs for the measurement of 5-HIAA in urine ranged from 1.2% to 3.9% and 3.2% to 7.6%, respectively. For urine samples from patients with known or suspected carcinoid tumors, results obtained by the automated method were highly correlated (r=0.988) with those from an established manual extraction method. For samples from autistic patients, urinary excretion of 5-HIAA was similar to that reported for healthy individuals. CONCLUSION: This SPE-HPLC method demonstrated lower imprecision and time per analysis than the manual solvent extraction method.