Urinary Excretion Of 5-hydroxyindoleacetic Acid Research Articles

Antioxidant, Antistress, Nootropic activity and its Correlation studies of aqueous extract of Punica granatum fruit estimated by Noninvasive biomarkers and Y-maze test in rodents

The memory loss associated with increased oxidative stress due to increased level of free radicals. Oxidative stress has been involved in several diseases includes cancer, atherosclerosis and neurodegenerative diseases.This study aimed to estimate the correlation of antioxidant and antistress activity with nootropic activity of aqueous extract of pomegranate (Punica granatum) by in-vivo noninvasive studies using rats. The in-vitro antioxidant activity was determined based on the ability of the Punica granatum to scavenge free radicals and lipid peroxidation inhibiting activity. The antistress effect of the aqueous extract of Punica granatum for 24h treatment (100 and 300mg/kg, p.o.) was evaluated by using the forced swim stress test in rats. The 24h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and ascorbic acid (AA) was determined in all groups under normal and stressed conditions by HPLC and spectrophotometric methods in all groups, were selected as noninvasive biomarkers. Nootropic activity activities of Punica granatum fruit extract were estimated as locomotor and working memory in rats in a Y-maze apparatus. Administration of aqueous extract of Punica granatum at a dose of 100 and 300mg/kg reduced the urinary metabolite levels. Punica granatum treatment showed significant dose dependent variation in non-invasive biomarker levels in urine samples of rats taken after 24h. The treatment with Punica granatum extracts improved the percentage entry of rats into safer zone, it means acquisition (learning) retention and retrieval (memory) were improved in rats compared to stress controls. Cognition determined by working memory and locomotor activity results were shown to be dose-dependent. The results of this study strongly suggestedantioxidant, antistress and nootropic activity effect of Punica granatumin rodents were correlated. The data obtained were analyzed by one-way ANOVA followed bytukey test. p<0.05 was considered to be significant. There is substantial evidence that flavonoids play an active role in providing antioxidant, antistress and nootropic activities of Punica granatum extracts. The findings of the present investigations indicate that the Punica granatum has significant antistress activity, which may be due to the immunostimulating property and increased resistance, nonspecifically, against all experimental stress conditions. The study provided scientific evidence for their utility as nootropic agents and to advocate their use in foods.

Ergot alkaloids reduce circulating serotonin in the bovine.

Ergot alkaloids can interact with several serotonin (5-hydroxytryptamine [5-HT]) receptors provoking many physiological responses. However, it is unknown whether ergot alkaloid consumption influences 5-HT or its metabolites. Thus, two experiments were performed to evaluate the effect of ergot alkaloid feeding on 5-HT metabolism. In exp. 1, 12 Holstein steers (260 ± 3 kg body weight [BW]) were used in a completely randomized design. The treatments were the dietary concentration of ergovaline: 0, 0.862, and 1.282 mg/kg of diet. The steers were fed ad libitum, kept in light and temperature cycles mimicking the summer, and had blood sampled before and 15 d after receiving the treatments. The consumption of ergot alkaloids provoked a linear decrease (P = 0.004) in serum 5-HT. However, serum 5-hydroxytryptophan and 5-hydroxyindoleacetic acid did not change (P > 0.05) between treatments. In exp. 2, four ruminally cannulated Holstein steers (318 ± 3 kg BW) were used in a 4 × 4 Latin square design to examine the difference between seed sources on 5-HT metabolism. Treatments were: control-tall fescue seeds free of ergovaline, KY 32 seeds (L42-16-2K32); 5Way-endophyte-infected seeds, 5 way (L152-11-1739); KY31-endophyte-infected seeds, KY 31 (M164-16-SOS); and Millennium-endophyte-infected seeds, 3rd Millennium (L108-11-76). The endophyte-infected seed treatments were all adjusted to provide an ergovaline dosage of 15 μg/kg BW. The basal diet provided 1.5-fold the net energy requirement for maintenance. The seed treatments were dosed directly into the rumen before feeding. The experiment lasted 84 d and was divided into four periods. In each period, the steers received seeds for 7 d followed by a 14-d washout. Blood samples were collected on day 0 (baseline) and day 7 for evaluating the treatment response in each period. A 24 h urine collection was performed on day 7. Similar to exp. 1, serum 5-HT decreased (P = 0.008) with the consumption of all endophyte-infected seed treatments. However, there was no difference (P > 0.05) between the infected seeds. The urinary excretion of 5-hydroxyindoleacetic acid in the urine was not affected (P > 0.05) by the presence of ergot alkaloids. In conclusion, the consumption of ergot alkaloids decreases serum 5-HT with no difference between the source of endophyte-infected seeds in the bovine.

Pattern of postruminal administration of l-tryptophan affects blood serotonin in cattle

Serotonin (5-HT) has many important functions in both central and peripheral nervous systems. Although it has been demonstrated that manipulation of serotonin metabolism is possible in many species, there is limited information about l-tryptophan (TRP), a serotonin precursor, in cattle, and these provide conflicting results. Furthermore, there is no study evaluating how different patterns of intra-abomasal infusion of TRP impact circulating 5-HT. The objective of this study was to evaluate if intra-abomasal infusion patterns of TRP can affect circulating 5-HT and other metabolites from TRP metabolism in the plasma and serum and circulating glucose and insulin in cattle. Eight ruminally cannulated Holstein steers were used in a replicated 4 × 4 Latin square design. Each received intra-abomasal water infusion (control) or intra-abomasal TRP infusion (50 mg/kg BW) in 3 different patterns: a pulse infusion once a day (pulse once), pulse infusion twice a day (pulse twice), or continuous infusion (continuous). For continuous treatment, the TRP dose was diluted in tap water and infused by a peristaltic pump (300 mL/h). To equalize conditions, the other treatments had a water infusion (300 mL/h). The steers were fed every 2 h, and blood was collected from a jugular vein catheter every 4 h for 24 h after the initial infusion. Urine produced during the 24 h period was collected. Serum and plasma TRP, 5-HT and kynurenine, plasma glucose, and serum insulin concentrations were analyzed. Urine was analyzed for concentrations of 5-hydroxyindoleacetic acid. Both serum TRP and kynurenine were increased (P < 0.05) by all TRP infusion treatments, but concentrations in pulse dose treatments were greater than those in continuous infusion. Serum 5-HT increased (P < 0.05) with both pulse TRP infusion treatments; however, the continuous TRP infusion did not increase the serum 5-HT. Plasma 5-HT, glucose, and insulin had a tendency to increase with TRP pulse infusions. The urinary 5-hydroxyindoleacetic acid excretion was highest for pulse dose treatments. An acute supply of TRP in 1 or 2 daily doses increases serum 5-HT and increases circulating glucose and insulin in cattle. The TRP and kynurenine concentrations are similar in plasma and serum. However, the serum 5-HT concentration is more responsive to TRP administration than plasma.

脳内5-hydroxytryptamine含量における非侵襲的マーカーとしての尿中5-hydroxyindoleacetic acid排泄量の測定 : 5,7-dihydroxytryptamineマイクロインジェクション後の脳-尿相関について

脳内5-hydroxytryptamine含量における非侵襲的マーカーとしての尿中5-hydroxyindoleacetic acid排泄量の測定 : 5,7-dihydroxytryptamineマイクロインジェクション後の脳-尿相関について

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50μmol/24hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden.

A 17-year-old male with a Small Bowel Neuroendocrine Tumor: flushing differential diagnosis

Background Neuroendocrine tumors (NETs) are heterogeneous neoplasms that originate from cells with a secretory function. Small bowel NETs (SB-NETs) are related to serotonin hypersecretion which causes: flushing, diarrhea, abdominal pain, bronchoconstriction and heart involvement, also known as carcinoid syndrome (CS). CS can be confused with an allergic reaction and thus should be considered as a differential diagnosis in the allergy consult. We present the case of a pediatric patient initially referred under the suspicion of food allergies.Case presentation We present the case of a 17-year-old male with evanescent non-pruriginous erythematous lesions- flushing that appeared with food consumption, associated with conjunctival injection, warmth and diaphoresis after the lesions disappeared. He denied abdominal pain, diarrhea, cough or wheezing. The 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion was elevated. The CT scan showed thickening of the distal ileum and multiple lesions on both hepatic lobules and the colonoscopy revealed a tumor in the ileocecal valve. Hepatic and intestinal biopsies reported a well-differentiated NET of the ileocecal valve with hepatic metastasis. He was started on octreotide and underwent a wide hepatectomy and right hemicolectomy with improvement of symptoms.Conclusions NETs can present as carcinoid syndrome (flushing, diarrhea, abdominal pain, wheezing), which constitutes vague symptomatology and represents a challenging diagnosis for physicians. They can be confused with an allergic reaction and the allergist should consider it as a differential diagnosis. Accurate diagnostic tests will help to diagnose NETs earlier and potentially prevent carcinoid heart disease, bowel obstruction, and improve quality of life and mortality in these patients.

Limited value for urinary 5-HIAA excretion as prognostic marker in gastrointestinal neuroendocrine tumours.

To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion is of prognostic value for overall survival (OS) in patients with a gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value with patient characteristics, ENETS/WHO grading, ENETS TNM staging and biomarkers. Data was collected from patients with a gastrointestinal NET or a NET with gastrointestinal metastases and available 5-HIAA excretion in 24-h urine samples. Laboratory results were stratified for urinary 5-HIAA and chromogranin A (CgA): <2× upper limit of normal (ULN), 2-10× ULN, or >10× ULN. For neuron-specific enolase (NSE), this was the reference range or >1× ULN. OS was compared using Kaplan-Meier and log-rank tests, and hazard ratios were calculated using Cox regression for univariate and multivariate analyses. A total of 371 patients were included, 46.6% female with a mean age of 59.9 years. OS was shortest in patients with urinary 5-HIAA excretion >10× ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10× ULN was a negative predictor (HR 1.62, 95% CI: 1.09-2.39). However, in multivariate analysis, only age (HR 1.04, 95% CI: 1.01-1.08), grade 3 disease (HR 5.09, 95% CI: 2.20-11.79), NSE >1× ULN (HR 2.36, 95% CI: 1.34-4.14) and CgA >10× ULN (HR 3.61, 95% CI: 1.56-8.34) remained as the predictors. Urinary 5-HIAA excretion >10× ULN is a negative predictor for OS. However, when added to other biomarkers and grading, it is no longer a predictor for OS. Therefore, it should only be determined to assess carcinoid syndrome and not for prognostic value.

Carcinoid tumors – retrospective analysis of patients hospitalized between 2001 and 2012 year in Department of Endocrinology and Diabetology of Ludwik Rydygier Collegium Medicum in Bydgoszcz

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) originate from diffuse endocrine system (DES). Over 50% of diagnosed neuroendocrine neoplasms (NENs) are carcinoid tumors, secreting mainly serotonine. The incidence of carcinoids in general population is estimated to be 2.9 cases/100000 inhabitants/year. In our study we aimed at analyzing retrospectively patients with diagnosed carcinoid tumors, hospitalized between the years 2001 and 2012 in the Department of Endocrinology and Diabetology of Nicolaus Copernicus University Collegium Medicum in Bydgoszcz. The study group consists of 39 patients (20 women and 19 men) aged between 36 and 70, with diagnosed carcinoid. All patients have determined chromogranin A concentration (CgA), urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) in 48-hours urine sample, urinary excretion of catecholamine hormones (norepinephrine, epinephrine and dopamine), vanillylmandelic acid (VMA) and homovanillic acid (HVA) in 24-hours urine sample. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and somatostatin receptor scintigraphy (SRS) with 99mTc-Depreotide have been performed. The diagnosis of the carcinoid tumor is often problematic because of its slow growth and uncharacteristic symptoms. And often the localization of the primary tumor cannot be determined. Somatostatin analogues can help to control symptoms of the carcinoid syndrome

Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence

Various stress hormones are responsible for bringing out stress-related changes and are implicated in learning and memory processes. The extensive clinical experience of angiotensin receptor blockers (ARBs) and direct renin inhibitor as antihypertensive agents provides anecdotal evidence of improvements in cognition. The neurochemical basis underlying the anti-stress and nootropic effects are unclear. This study was aimed to determine the effects of aliskiren, valsartan and their combination on the neuromediators of the central nervous system (CNS) and periphery as well as on cognitive function. Groups of rats were subjected to a forced swim stress for one hour after daily treatment with aliskiren, valsartan and their combination. The 24 h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), 6-β-hydroxycortisol (6-β-OH) cortisol and homovanillic acid (HVA) was determined in all groups under normal and stressed conditions. Nootropic activity was studied using cook's pole climbing apparatus and acetylcholinesterase (AChE) inhibitory activity by Ellman's method. Administration of aliskiren (10 mg/kg), valsartan (20 mg/kg) and their combination at a dose of 5 and 10 mg/kg respectively reduced the urinary metabolite levels. Further, all drugs showed significant improvement in scopolamine-impaired performance and produced inhibition of the AChE enzyme. The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination.

Serotonin Metabolism in the Placenta in Exacerbation of Herpesvirus Infection during Pregnancy

Serotonin metabolism in the blood and placental homogenate was studied in pregnancy aggravated by exacerbation of herpesvirus infection. Blood serotonin content in pregnant patients increased with increasing herpesvirus antibody titers and reduction of monoamine oxidase activity. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) decreased. The decrease of monoamine oxidase activity in placental homogenate led to an increase of serotonin level, which was paralleled by destruction of mitochondria in the syncytiotrophoblast, suppression of BCL-2 protein activity, and increase of caspase-3 level.

Evaluation of enalapril affecting the renin-angiotensin system in normal and stress-induced rats based on urinary metabolites of amines and cortisol

The renin-angiotensin system is distributed centrally as well as peripherally, which works in association with SNS and HPA in stress. Angiotensin is considered one of the principal hormones for bringing out stress-related changes. To find the influence of enalapril on the neuromediator of CNS and periphery, the present work was carried out. The assessment of the transmitter levels was done by estimating major urinary stress metabolites like vanillylmandelic acid, 5-hydroxyindoleacetic acid, 6-β-hydroxycortisol and homovanillic acid in normal and stress-induced conditions and also in the absence and presence of enalapril treatment in rats. Groups of rats were subjected to a forced swim stress one hour after daily treatment of enalapril. The 24 h urinary excretion of vanillylmandelic acid, 5-hydroxyindoleacetic acid, 6-β-hydroxycortisol and homovanillic acid was determined in all groups under normal and stressed-induced conditions. Daily administration of enalapril at doses of 3, 10 and 30 mg/kg/body weight inhibited the stress-induced urinary biochemical changes. However, treatment with enalapril in normal conditions increased the excretion of all selected metabolites. It can be speculated that enalapril prevented stress-induced increases of adrenergic, serotonergic and cortical mechanisms.

Growth of a solitary pulmonary nodule after 6 years diagnosed as oncocytic carcinoid tumour with a high 18‐fluorodeoxyglucose (18F‐FDG) uptake in positron emission tomography‐computed tomography (PET‐CT)

Pulmonary carcinoid tumour is low-grade neuroendocrine malignancy that is seen 1%-2% of all lung neoplasms. Oncocytic carcinoid type is a rarely seen variant of pulmonary carcinoids. As carcinoid tumours have hypometabolic activity, they usually have lower 18-fluorodeoxyglucose (18F-FDG) uptake than expected for lung carcinoma on positron emission tomography (PET). A 45-year-old non-smoking man had a stable solitary pulmonary nodule followed for 6years; the tumour remained the same size (1.5×2.4cm) during this period. The patient was admitted to the hospital with complaints of repetitive sneezing and rhinorrhoea. He also experienced flushing and bronchospasm. His chest X-ray revealed a minimal increase in the size of the solitary pulmonary nodule (2.0×2.8cm). In PET-computed tomography (CT), the parenchymal nodule in the anterior segment of the right lung had a standard uptake value of 38.0mg/mL, which was interpreted as a malignant nodule. He underwent fibre-optic bronchoscopy, but cytology showed no evidence of malignancy. Right upper and middle bilobectomy was performed, and a pulmonary carcinoid tumour with an oncocytic subgroup was diagnosed. The diagnosis of carcinoid syndrome was further confirmed by an elevated 24-h urinary excretion of 5-hydroxyindoleacetic acid. We present a rare case of an oncocytic carcinoid tumour with an increase in the size of a solitary pulmonary nodule after 6years' follow-up. In addition, PET-CT showed a very high 18F-FDG uptake in this patient, which is an unexpected finding with a pulmonary carcinoid tumour.

Urinary Excretion of 5-Hydroxyindoleacetic Acid, Serotonin and 6-Sulphatoxymelatonin in Normoserotonemic and Hyperserotonemic Autistic Individuals

Objective: A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Methods: Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. Results: In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. Conclusions: The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production.

Tricuspid and pulmonary valve involvement in carcinoid heart disease

A 55-year-old woman with a history of proven carcinoid syndrome due to an enterochromaffin ileal tumour was evaluated with transthoracic echocardiography for dyspnoea on exertion. The patient had flushing and severe diarrhoea. Urinary excretion of 5-hydroxyindoleacetic acid was 250 mmol/L per 24 hours. Treatment with a somatostatin analogue had been initiated 5 months earlier. Physical examination revealed a 3/6 systolic ejection murmur at the left upper sternal border. No signs of right-sided heart failure were found. The electrocardiographic data were within normal limits. Transthoracic two-dimensional echocardiography revealed restricted motion of the septal and anterior tricuspid valve leaflets both during systole and diastole, leading to an eccentric jet and mild to moderate tricuspid regurgitation (Fig. 1 and Movie 1). Continuous wave (CW) Doppler documented an associated tricuspid stenosis with a mean diastolic gradient of 5 mmHg (Fig. 2). The pulmonary valve was also involved, defined by a limited excursion of the pulmonary valve leaflets without a complete coaptation. CW Doppler of the pulmonary valve demonstrated the presence of both pulmonary stenosis defined by a mean gradient of 40mmHg (Fig. 3) and pulmonary regurgitation (Movie 2). No patent foramen ovale was found at contrast echocardiography. Pulmonary and tricuspid valves were replaced with bioprosthetic valves. A surgical view of the tricuspid and pulmonary valve revealed immobile, thickened and retracted pulmonary and tricuspid valves leaflets (Figs. 4 and 5). Characteristic echocardiographic features of advanced carcinoid heart disease include thickening, retraction of immobile tricuspid valve leaflets with associated tricuspid regurgitation in 90% of cases and pulmonary involvement, mainly immobility of the pulmonary valve cusps, in at least 50% of cases [1]. Contrast transthoracic echocardiography should be performed systematically, searching for a right-to-left atrial shunt through a patent foramen ovate [2].

FINDINGS IN ROUTINE LABORATORY EXAMINATION IN PROGRESSIVE MYOCLONUS EPILEPSY

Thirty-one patients suffering from progressive myoclonus epilepsy, (also called Unverricht-Lundborg's disease) without Lafora bodies, were examined to check the findings reported in literature and to chart out the main abnormalities in routine laboratory findings. Many alterations could be pointed out, but a high proportion of them were due to factors which are secondary to the syndrome of progressive myoclonus epilepsy: continuous anticonvulsive medication; immobilization; frequent infections; and the patient's poor nutritional condition. The most remarkable finding, and the only one which supported the abnormality reported earlier, was the raised excretion of indican which could not be explained by fermentation in the bowels. The urinary 5-hydroxyindoleacetic acid excretion was a little low, but still within the normal range. The tryptophan and 5-hydroxytryptamine metabolism deserves further investigation in attempting to discover the aetiology of progressive myoclonus epilepsy.

HPLC–mass spectrometry method for quantitative detection of neuroendocrine tumor markers: Vanillylmandelic acid, homovanillic acid and 5-hydroxyindoleacetic acid

Background The urinary excretion of vanillylmandelic acid (VMA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) can be increased in the presence of neuroblastic and carcinoid tumors. The former is characterized by defective catecholamine metabolism which results in high urinary levels of VMA and HVA. The latter shows an altered metabolism of tryptophan and an increased synthesis of serotonin, producing high 5-HIAA urinary concentrations. Methods We describe an HPLC-tandem mass spectrometric method for the simultaneous quantification of VMA, HVA and 5-HIAA in human urine. The chromatographic separation is performed on a reversed-phase C18 column. Instrumental analysis is performed on a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer. Results The method is fast and does not require sample pre-treatment. Multiple calibration curve exhibited consistent linearity and reproducibility. Linear responses were observed in the concentration range 0–50 mg/l for each analyte. Limits of detection were 0.001 mg/l for VMA, 0.015 mg/l for 5-HIAA and 0.050 mg/l for HVA with a signal-to-noise ratio of 3. Limits of quantification were 0.005 mg/l for VMA, 0.050 mg/l for 5-HIAA and 0.1 mg/l for HVA with a signal-to-noise ratio of 10. Conclusions This method can be proposed as a tool for neuroendocrine tumor markers detection.

The neuroendocrine tumors of the ileum

AbstractNeuroendocrine tumors arise from the diffuse neuroendocrine system and secrete several peptides and bioactive amines (serotonin, histamine, dopamine, norepinephrine, corticotropin, calcitonin, bradykinin, kalikrein, gastrin, cholecystokinin, prostaglandins). The most common occurrence site of neuroendocrine tumors is the ileum. The symptoms of small bowel carcinoids are represented by intermittent intestinal obstruction and carcinoid syndrome. Presence of the carcinoid syndrome usually indicates hepatic or retroperitoneal metastases. The typical carcinoid syndrome is characterized by flushing, diarrhea, nonspecific abdominal pain and bronchospasm. The diagnosis of small bowel tumors is often difficult due to their rarity and the nonspecific and variable nature of the presenting signs and symptoms. The most useful initial diagnostic test for the carcinoid syndrome is to measure 24-hour urinary excretion of 5-hydroxyindolacetic acid (5 HIAA), which is the end product of serotonin metabolism. Capsule endoscopy is a more recent diagnostic tool. Surgery is the radical form of curative therapy for carcinoid tumors. Numerous therapies are available for palliation including surgery, pharmacologic therapy, interventional radiologic therapy, embolization and chemoembolization of hepatic metastases, immunotherapy (Interferon alfa) and chemotherapy. We carefully reviewed the available literature on this topic before beginning our study.

Increase of Urinary 5-Hydroxyindoleacetic Acid Excretion but Not Serum Chromogranin a Following Over-The-Counter 5-Hydroxytryptophan Intake

5-hydroxyindoleacetic acid (5-HIAA) excretion is commonly measured for biochemical detection of carcinoid tumours. A 77-year-old woman was referred for elevated 24 h urine 5-HIAA excretion (510 micromol/day; normal is less than 45 micromol/day) and serum chromogranin A (CgA) (72.1 U/L; normal is less than 18 U/L), both subsequently normalized after discontinuation of 5-hydroxytryptophan (5-HTP). 5-HTP, a precursor of serotonin, is not commonly listed as a substance that increases 5-HIAA levels in urine. The effect of 5-HTP on CgA has not been previously described. To determine whether, and to what extent, oral 5-HTP increases urine 5-HIAA excretion and serum CgA levels in healthy volunteers. A randomized, prospective, double-blind, placebo-controlled crossover study, with a four-day washout period, was performed in a general community setting. Eight healthy subjects aged 22 to 58 years were recruited by advertising. Bedtime ingestion of 5-HTP 100 mg/day was compared with placebo ingestion for 10 days. Twenty-four hour urine excretion of 5-HIAA and serum CgA were the main outcome measures. Median (range) urinary 5-HIAA excretion was 204 micromol/day (22 micromol/day to 459 micromol/day) during 5-HTP intake, compared with 18 micromol/day (12 micromol/day to 36 micromol/day) during placebo intake (P=0.017). 5-HTP did not affect clinical symptoms or serum CgA levels. Oral 5-HTP increases urinary 5-HIAA excretion with considerable interindividual variation. In a small number of subjects, oral 5-HTP did not affect serum CgA levels. Therefore, increased 5-HIAA levels with normal CgA levels may suggest 5-HTP ingestion. The use of over-the-counter 5-HTP should be excluded as the cause of increased urinary 5-HIAA levels before initiating diagnostic tests to search for a carcinoid tumour. 5-HTP should be added to popular references as a substance that may cause increased 5-HIAA excretion.

Primary carcinoid tumor of the bilateral testis associated with carcinoid syndrome

Carcinoid tumors derived from neuroendocrine cells can release serotonin and other vasoactive substances into the systemic circulation, resulting in carcinoid syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We describe a case of carcinoid syndrome arising from a primary testicular carcinoid tumor. A 21-year-old male patient presented with facial flushing and diarrhea for 5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated with carcinoid tumor in both testes. Following bilateral orchiectomy, the patient's facial flushing and diarrhea disappeared.

Acute renal failure in carcinoid syndrome crisis

The release of vasoactive substances into the circulation is the major contributing factor for symptoms in the carcinoid syndrome. Acute renal failure has been described in some patients with carcinoid tumors undergoing chemoembolisation of liver metastases and treatment with interferon-α. We describe a patient without such treatment and acute renal failure during carcinoid syndrome crisis. A 55 year old man with a known metastatic carcinoid tumor was admitted with persisting facial flushing over many hours. He has been operated on a primary non-functioning neuroendocrine tumor of the left lung in 1988. During the last months facial flushing appeared periodically lasting for up to two hours with spontaneous remission. At hospital admission flushing was accompanied by tachycardia of 120–140 beats per minute, fever up to 38.2 degrees Celsius and severe weakness. Blood-pressure was in the low-normal range. Serum creatinine increased from 1.0mg/dl up to 5.9mg/dl within 24 hours. N-acetyl-cystein-(NAC)-activated creatinkinase (CK) and the isoenzyme CK-MB were markedly elevated (2342 U/L and 4630 U/L, respectively). Despite intravenous fluid therapy the patient developed anuria. Hemodialysis was performed one time. Octreotide was given intravenously in a dosis of 100µg/hour intravenously. This high-dose treatment with octreotide could interrupt the carcinoid syndrome crisis after 18 hours. A phase of polyuria was followed by complete normalisation of renal function. After switching to subcutaneous delivery of octreotide (3×100µg/day) symptoms of the carcinoid syndrome did not reoccur. Serotonine values in serum and diurnal urinary excretion of 5-hydroxyindoleacetic acid were extremely elevated. Magnetic resonance imaging demonstrated extensive liver metastases while octreotide scan confirmed metastatic bone disease. Echocardiography could show only subtle changes of carcinoid heart diseae.