peptide-yy and Constipation

Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

Topics: Aged; Carcinoid Tumor; Chronic Disease; Constipation; Female; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Peptide YY

Primary carcinoid tumors are rare neoplasms of the ovary. Of the 4 histologic subtypes, ovarian carcinoid tumors with insular patterns produce carcinoid syndrome in approximately one third of cases, versus strumal and trabecular carcinoids which very rarely cause typical carcinoid syndrome. A unique presentation of ovarian carcinoid tumors with concurrent severe constipation has been reported, which is thought to represent a new carcinoid syndrome. The proposed mechanism is the production of peptide YY by the tumor, a gastrointestinal hormone responsible for decreasing gut motility. We report a case of a 34-yr-old white woman who presented with constipation and weight loss for 1 yr, and was found to have a unilateral ovarian strumal carcinoid, which produced peptide YY as demonstrated by immunohistochemistry. The 13 previous case reports of ovarian carcinoids with constipation are reviewed and the clinicopathologic features are discussed. This report and literature review further solidifies this entity as a new type of carcinoid syndrome.

Topics: Adult; Carcinoid Tumor; Comorbidity; Constipation; Female; Gastrointestinal Motility; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Peptide YY; Severity of Illness Index; Struma Ovarii; Syndrome; Treatment Outcome

Ovarian carcinoid is a rare tumor accounting for approximately 0.1% of all ovarian malignancies. We describe a case of peptide-YY-producing strumal carcinoid of the ovary associated with severe constipation. A 48-year-old woman was found to have a pelvic mass on ultrasonography when she visited her primary doctor for a health check-up. She was thus referred to our department. Magnetic resonance imaging revealed a solid right ovarian tumor 60 × 50 mm in size. The patient underwent a right adnexectomy and was histopathologically diagnosed as having strumal carcinoid of the ovary. On immunohistochemical examination, the tumor cells were positive for peptide YY. The patient's constipation resolved rapidly after surgery. Based on her clinical course, her constipation was considered to have been caused by the strumal carcinoid of the ovary. The clinical course of this case supports the previously recognized correlation between peptide-YY-producing ovarian carcinoid and constipation.

Topics: Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; Ovary; Peptide YY; Severity of Illness Index; Struma Ovarii

Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood.. We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS.. Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined.. Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group.. Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Topics: Adult; Analysis of Variance; Case-Control Studies; Catheterization; Cholecystokinin; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Humans; Male; Middle Aged; Motilin; Neuropeptide Y; Pain Threshold; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Pressure; Statistics, Nonparametric; Stomach; Vasoactive Intestinal Peptide

To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.. Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.. The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm(2) in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.. The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Biopsy; Case-Control Studies; Colonoscopy; Constipation; Diarrhea; Endocrine Cells; Female; Glucagon-Like Peptides; Humans; Hyperalgesia; Ileum; Image Interpretation, Computer-Assisted; Immunohistochemistry; Irritable Bowel Syndrome; Male; Middle Aged; Pain Measurement; Pancreatic Polypeptide; Peptide YY; Serotonin; Somatostatin; Somatostatin-Secreting Cells; Surveys and Questionnaires; Visceral Pain; Young Adult

The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients.. To investigate a possible abnormality in the colonic endocrine cells of IBS patients.. A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis.. Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification.. The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

Topics: Adolescent; Adult; Aged; Colon; Constipation; Diarrhea; Female; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Peptide YY; Serotonin; Young Adult

Primary ovarian carcinoid tumors are rare. It has been reported that constipation was a presenting symptom in some patients with ovarian carcinoid. A case of strumal carcinoid of the ovary with contralateral clear cell adenocarcinoma of the ovary discovered with a complaint of constipation is described. Constipation was dramatically improved by resectioning the tumor. The tumor cells were positive for peptide YY (PYY) in the carcinoid component, but not in any other components. The present case could provide evidence of the correlation between constipation and PYY that has been reported elsewhere. Interestingly, the constipation caused by PYY also helped in discovering epithelial ovarian cancer.

Topics: Adenocarcinoma, Clear Cell; Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Ovary; Peptide YY

The gut hormone peptide YY is abundant in the colonic mucosa. Circulating PYY inhibits gastrointestinal motility and decreases food intake. The aim was to determine whether colectomy decreases PYY release in patients with slow transit constipation.. Plasma PYY concentrations were measured in 10 patients with slow transit constipation before and 3-24 months after total abdominal colectomy with ileorectal anastomosis, and in 8 healthy controls. A liquid meal was infused intraduodenally to stimulate PYY release.. Postprandial PYY significantly (P < 0.05) increased from a basal value of 15.6 +/- 1.8 pM to a peak of 71.2 +/- 11.6 pM after colectomy. Basal and postprandial plasma PYY concentrations were not significantly different from the results before surgery. Fasting, but not postprandial, plasma peptide YY after colectomy was significantly higher than that in healthy volunteers, 10.9 +/- 0.9 pM.. Despite removal of a major source of PYY-secreting cells, colectomy with ileorectal anastomosis does not induce major impairment of PYY release in slow transit constipation.

Topics: Adult; Aged; Anastomosis, Surgical; Colectomy; Constipation; Female; Gastrointestinal Transit; Humans; Ileum; Male; Middle Aged; Peptide YY; Rectum

To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls.. We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy.. The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY.. IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.

Topics: Adult; Aged; Biopsy; Case-Control Studies; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Humans; Male; Middle Aged; Neuropeptide Y; Peptide YY; Substance P; Vasoactive Intestinal Peptide

A case of a 58-year-old woman with ovarian carcinoid exhibiting double function is reported. She had suffered from constipation and hirsutism before surgery. Pathological examination revealed that many carcinoid tumor cells were immunohistochemically positive for peptide YY, which inhibits intestinal motility and many peripheral steroid cells. After surgery the patient recovered from constipation immediately. Although the serum level of testosterone also immediately decreased, hirsutism remained for about 2 years. These clinical manifestations are considered to be due to peptide hormone-producing tumor parenchymal cells and testosterone-producing functioning stromal cells. This is the first report of clinically manifested double-functioning ovarian carcinoid; one function is due to tumor cells themselves and another function is due to stromal cells.

Topics: Biomarkers, Tumor; Carcinoid Tumor; Constipation; Cytoplasmic Granules; Fallopian Tubes; Female; Hirsutism; Humans; Hysterectomy; Middle Aged; Neurosecretory Systems; Ovarian Neoplasms; Peptide YY; Testosterone; Treatment Outcome

Patients with idiopathic slow-transit constipation comprise a small proportion of the total population complaining of constipation. The purpose of this review is to present an update of pathophysiology of this disorder and its application in clinical management.. Medline was used to search English language articles published up to the end of September 2002 on the subject of slow-transit constipation.. Patients with idiopathic slow-transit constipation can be divided into 2 subgroups: 1. patients with normal proximal gastrointestinal motility and with onset of constipation in connection with childbirth or pelvic surgery. This subgroup may benefit from consideration of surgical treatment; 2. patients who have a dysfunctional enteric nervous/neuroendocrine system and exhibit colonic dysmotility as part of a generalised gastrointestinal dysmotility. Surgical approach in this subgroup seems to be unhelpful and medical treatment appears to be a better approach.

Topics: Autonomic Nervous System; Chronic Disease; Constipation; Gastrointestinal Transit; Humans; Neurosecretory Systems; Peptide YY; Substance P

Primary carcinoid tumor of the ovary is uncommon and represents less than 0.1% of ovarian malignancy. Recently, it was reported that the strumal carcinoid tumor may be complicated by severe constipation as one symptom of the carcinoid syndrome.. A 50-year-old nulliparous woman complained of persisting constipation and abdominal distention with pelvic mass, raising the possibility of ovarian tumor. The sugically resected tumor was diagnosed as strumal carcinoid tumor. Her long-lasting severe constipation completely disappeared after tumor removal but recurred with recurrent hepatic disease. The tumor cells were positive for PYY, a peptide hormone that has a strong inhibitory effect on intestinal motility, by immunohistochemical stain.. Our case provides the more convincing information to indicate that PYY protein, produced by ovarian tumor cells in the trabecular carcinoid component, may be associated with severe constipation.

Topics: Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Ovarian Neoplasms; Peptide YY

Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation.. Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls.. Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying.. Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.

Topics: Adult; Aged; Cholecystokinin; Constipation; Eating; Fasting; Female; Gallbladder; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Middle Aged; Peptide YY

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility.. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal.. Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected.. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Topics: Adult; Cholecystokinin; Constipation; Dilatation; Female; Gallbladder Emptying; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Male; Middle Aged; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Pressure; Rectum; Stress, Mechanical

Functioning ovarian carcinoid tumors are well known to cause carcinoid syndrome. Recently, strumal and trabecular ovarian carcinoid tumors are reported to cause severe constipation possibly because of tumor-producing peptide YY (PYY). We studied a case of primary ovarian strumal carcinoid who had had severe constipation until the tumor was removed by surgical operation. Immunohistochemically, many tumor cells were strongly positive for PYY. By Northern blot and reverse transcription polymerase chain reaction analyses, PYY mRNA was expressed in a complete form as detected in normal human colon mucosa. From these findings, an ovarian strumal carcinoid is strongly suggested to express complete PYY mRNA and therefore complete PYY protein that results in severe constipation.

Topics: Blotting, Northern; Carcinoid Tumor; Constipation; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Peptide YY; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Struma Ovarii

The aim of the present study was to investigate the colonic endocrine cells in patients with slow-transit constipation, to ascertain the presence of a possible abnormality.. Ten patients with chronic slow-transit constipation were investigated. As controls, macroscopically and histologically normal tissues from the colon of 12 patients were examined. These patients had polyps, prolapsis, chronic diverticulitis, volvulus, and haemorrhoids. The endocrine cells were stained by immunocytochemistry and quantified by computerized image analysis.. There were significantly fewer enteroglucagon- and serotonin-immunoreactive cells in patients with chronic slow-transit constipation. There was no statistically significant difference between patients and controls with regard to the number of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and somatostatin-immunoreactive cells. The cell secretory indexes (CSI) of enteroglucagon- and somatostatin-immunoreactive cells were significantly decreased. There was no statistically significant difference in the CSI between the patients and controls with regard to PYY-, PP-, and serotonin-immunoreactive cells.. The changes in colonic endocrine cells in patients with slow-transit constipation may be one cause of the decreased motility in the colon and consequent development of constipation.

Topics: Adult; Aged; Biopsy; Chronic Disease; Colon; Colonic Diseases, Functional; Constipation; Enteroendocrine Cells; Female; Gastrointestinal Motility; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Middle Aged; Peptide YY; Serotonin; Statistics, Nonparametric

We report a patient with primary trabecular carcinoid of the ovary with severe constipation probably due to peptide YY production by the tumor. A 43-year-old female had complained of severe constipation for several months and was found to have a left ovarian tumor. The surgically resected tumor was diagnosed as trabecular carcinoid by light microscopic examination. The carcinoid tumor cells were intensely and uniformly stained by the Grimelius technique. Immunohistochemically, the tumor cells were strongly positive for peptide YY, which has a strong inhibitory action on intestinal motility. The patient has been free from constipation since the removal of the tumor. The present case supports previously reported findings that not typical carcinoid syndrome but rather severe constipation accompanies primary trabecular carcinoid of the ovary, and that peptide YY is presumably the cause of the constipation.

Topics: Adult; Carcinoid Tumor; Constipation; Female; Gastrointestinal Hormones; Humans; Ovarian Neoplasms; Peptide Biosynthesis; Peptide YY; Teratoma

Five patients with ovarian carcinoid who had severe constipation for a long period preoperatively showed marked reduction of this symptom postoperatively. Because this phenomenon was believed to be caused by some biologically active substance rather than a mechanical effect of the tumor, reactivity to 17 amine and peptide hormones was studied immunohistochemically in these patients. Numerous peptide YY (PYY)-positive cells were detected, with PYY-positive cells representing more than 50% of all carcinoid tumor cells in each patient. PYY, which has a pharmacologic inhibitory action on intestinal motility, was presumably the cause of the constipation in these patients.

Topics: Adult; Aged; Carcinoid Tumor; Constipation; Female; Gastrointestinal Motility; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Peptide Biosynthesis; Peptide YY