Urinary 5-hydroxyindoleacetic Acid Research Articles

Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease

Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease

Hepatic Artery Embolization for Control of Symptoms, Octreotide Requirements, and Tumor Progression in Metastatic Carcinoid Tumors

Hepatic artery embolization (HAE) has been utilized for treatment of advanced hepatic carcinoid metastases, with promising symptom palliation and tumor control. Our institution employs transcatheter HAE using Lipiodol/Gelfoam for treatment of carcinoid hepatic metastases, and this report presents our experience with twenty-four patients, examining symptom control, quality-of-life, octreotide dependence, and tumor progression. Twenty-four (11 male, 13 female, mean age = 59.4 ± 2.5 yr) patients with carcinoid and unresectable hepatic metastases, confirmed by urinary 5-hydroxyindole acetic acid (5-HIAA) measurement and biopsy, were treated with Lipiodol/Gelfoam HAE from 1993–2001. Median follow-up was 35.0 months. Before HAE, 14 patients (58.3%) had malignant carcinoid syndrome, with symptoms quantified using our previously reported Carcinoid Symptom Severity Score, and 13 patients (54.2%) required octreotide for symptom palliation. Following treatment, symptom severity, octreotide dose, and tumor response were measured. Asymptomatic patients did not develop symptoms or require following treatment. Hepatic metastases remained stable (n = 4) or decreased (n = 19) in 23 patients (95.8%). Mean pretreatment Symptom Severity Scores (3.8 ± 0.2), decreased to 1.4 ± 0.1 post-treatment ( P < 0.00001), with 64.3% of patients becoming asymptomatic. Mean pretreatment octreotide dosages (679.6 ± 73.0 μg/d), decreased to 262.9 ± 92.7 μg/d ( P = 0.0024) post-treatment, with 46.2% of patients discontinuing octreotide. There were no treatment-related serious complications or deaths. This study demonstrates that Lipiodol/Gelfoam HAE produces excellent control of malignant carcinoid syndrome, allowing patients to decrease or eliminate use of octreotide, while controlling hepatic tumor burden. ( J Gastrointest Surg 2002;6:664–670)

Use of octreotide and lanreotide in the treatment of symptomatic non-resectable carcinoid tumours.

Carcinoid tumours are rare neoplasms that secrete hormones and biogenic amines, most commonly serotonin. Octreotide and long acting lanreotide are found to be useful in the management of carcinoid syndrome by its interaction with somatostatin receptor, found on the carcinoid tumour. The aim of this study is to look at the efficacy of octreotide and long acting lanreotide in the treatment of symptomatic non-resectable carcinoid tumours. The effects of octreotide and long-acting lanreotide were studied in 10 patients with symptomatic non-resectable carcinoid tumours. Symptom improvement occurred in nine of 10 patients. Three patients responded only to octreotide, three patients responded to both octreotide and long-acting lanreotide and three patients only responded to long-acting lanreotide. Slight reductions in 24-h urine 5-hydroxyindoleacetic acid levels occurred in three of six patients but no patients were found to have objective tumour regression on computed tomography scan. Octreotide and long-acting lanreotide are useful palliative treatments for the control of symptoms in patients with non-resectable carcinoid tumours but there is no evidence of tumour stasis.

Urinary 5-hydroxyindoleacetic acid excretion and kaolin ingestion after a single administration of cisplatin in the delayed emesis rat model

From Volume 20 (2006), this title is published by Society of Integrated Sciences (International Medart, PO Box 37, 814 99 Bratislava 1, Slovak Republic, E-mail: publisher@nel.edu, Fax: +41 13553207).

Prospective study of the ability of histamine, serotonin or serum chromogranin A levels to identify gastric carcinoids in patients with gastrinomas

Chronic hypergastrinaemia causes gastric enterochromaffin cell proliferation and carcinoid tumours. The only reliable means to diagnose enterochromaffin cell changes/carcinoids is by biopsy. To assess whether serum histamine, chromogranin A or serotonin and urinary N-methylimidazoleacetic acid or 5-hydroxyindoleacetic acid correlate with advanced enterochromaffin cell changes or gastric carcinoids in patients with gastrinomas. Consecutive patients (n=145) had the above assays and endoscopy with gastric biopsies. Lower N-methylimidazoleacetic acid and chromogranin A levels (P < 0.0001) occurred in disease-free patients. In patients with active disease, the fasting serum gastrin levels correlated (P < 0.0001) with both chromogranin A and N-methylimidazoleacetic acid levels. Chromogranin A (P=0.005), but not N-methylimidazoleacetic acid, serotonin, 5-hydroxyindoleacetic acid or histamine levels, correlated with the enterochromaffin cell index. Carcinoids, but not advanced enterochromaffin cell changes only, were associated with higher chromogranin A and N-methylimidazoleacetic acid levels. Serum chromogranin A levels and urinary N-methylimidazoleacetic acid levels, but not serum histamine or serotonin or urinary 5-hydroxyindoleacetic acid, correlate with the presence of gastric carcinoids. However, no assay identified patients with advanced enterochromaffin cell changes only with high sensitivity/specificity. Thus, N-methylimidazoleacetic acid and chromogranin A levels are unable to identify patients with advanced changes in enterochromaffin cells and therefore neither can replace routine gastric biopsies.

Treatment of metastatic carcinoid tumours with octreotide

It was previously reported that treatment of metastatic carcinoid tumours with octreotide resulted in complete histological regression of such tumours in women.1 Previous cases of octreotide-related regression in carcinoid tumour masses were also reported.2-4 Our recent observation of a patient with hepatic metastases and carcinoid syndrome revealed that even though no discernible regression in tumour mass was found, octreotide treatment led to rapid improvement in hepatic function. A 79-year-old man was admitted to our hospital in November 2000, with a one-month history of facial flushing, headache and pressure in his ears. These attacks lasted 1–2 minutes and occurred several times a day. On examination, a purplish-red facial appearance, conjunctival hyperaemia and an enlarged liver were noted. Cardiac auscultation was within normal limits. Laboratory tests indicated hepatocellular damage and hepatic dysfunction (Table 1). He had no history of heavy alcohol consumption. Serological tests were negative for hepatitis A, B and C viruses. MRI of the abdomen revealed multiple metastases in the liver and multiple lymph nodes up to 2 cm in diameter in the para-aortic area. A liver biopsy was not attempted because of the prolonged partial thromboplastin time. His urinary 5-hydroxyindoleacetic acid level was elevated at 1326 μmol/24 h (normal range: 10.4–31.2). Imaging studies with CT and MR showed no evidence of a primary tumour. Because of the severity of the carcinoid symptoms and signs indicating hepatic dysfunction, we decided to treat this patient with a somatostatin analogue. Octreotide 50 μg three times daily was begun. During a two-week follow-up, the carcinoid symptoms markedly improved. In addition, hepatic function tests noticeably improved. A repeat MRI three weeks after the start of treatment showed no evidence of mass regression. This patient is on follow-up and octreotide treatment is continuing at the same dose for 12 months. The urinary 5-hydroxyindoleacetic acid level decreased to 271 μmol/24 h at month 4 of treatment. Abdominal MRI at 6 and 12 months of treatment showed no evidence of regression in hepatic and intra-abdominal lymph node metastases. He remains well and is still free of symptoms. Serial biochemical evaluation showed no evidence of deterioration in liver function. It is well known that somatostatin analogues have antiproliferative and antimitotic actions. The effect on liver function tests in our patient may not be explained by the decrease in tumour bulk, although we cannot exclude radiographically undetectable tumour regression. Somatostatin and analogues may have direct and indirect effects on hepatocytes and non-parenchymal liver cells.5, 6 Growth factors are able to modify hepatocyte proliferation in vivo, i.e. transforming growth factor β-1 produced by non-parenchymal liver cells is able to inhibit hepatocyte proliferation.7 Inhibitory effects of octreotide on the release of paracrine/growth factors from tumour cells might explain the recovery of liver function in the short term. Whatever the cause, octreotide led to symptomatic and functional recovery of metastatic carcinoid syndrome in our patient.

Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide.

To demonstrate that liver metastases by radically resected atypical carcinoids of the lung can be effectively treated by new somatostatin analogs. Between January 1977 and December 1999, 126 patients affected by bronchial carcinoids were submitted to a radical resection of the lung. Seven of them (5.5%) presented liver metastases 27, 22, 14, 18, 16, 12 and 9 months after surgery: carcinoid syndrome (CS) was ever present. 111In-DTPA-pentetreotide scintigraphy (Octreoscan) and ultrasound guided biopsy were performed in all cases, and the presence of somatostatin receptors sst2 was demonstrated by polymerase chain reaction (PCR) method. Five patients refused the proposed chemotherapy, and liver alcoholization was not feasible. Octreotide was administered at the dose of 1500 microg/daily subcutaneously. CS was controlled and also high urinary 5-hydroxyindoleacetic acid values returned to normal after a median of 7 days (range 4-10 days) of medical treatment. No important side effects were registered, and a good quality of life was observed. The patients are alive and well at 51, 36, 24, 24, 23, 19, and 16 months after the diagnosis of the metastases, respectively. In two cases ultrasounds revealed the reduction and in one case the complete resolution of the liver lesion. Octreotide is effective in controlling symptoms of CS of patients with liver metastases of resected atypical bronchial carcinoid. The efficacy of the drug is due to the presence of sst2 somatostatin receptors in the pathologic tissue, as demonstrated by PCR method. The positivity to Octreoscan depends on the presence of the same receptors. Octreoscan may be used in the follow-up of these neuroendocrine neoplasms of the lung. A positivity to Octreoscan is predictive for an effective therapy with octreotide.

Local blood serotonin and soluble P-selectin levels during percutaneous transluminal balloon angioplasty and primary stenting of the iliac artery

The activation of platelets or leukocytes plays an important role in development of intimal hyperplasia. We investigated whether the local blood serotonin and soluble P-selectin levels changed during endovascular therapy of the iliac artery. Blood samples were obtained from the iliac artery of 18 lower limbs undergoing percutaneous balloon angioplasty alone (8 limbs, group I) or percutaneous balloon angioplasty and primary stenting (10 limbs, group II). The serotonin levels in platelet-poor plasma were measured in all limbs. In group I the urinary level of the serotonin metabolite 5-hydroxyindoleacetic acid was also measured 24 hours before and 24 hours after the procedures. The soluble P-selectin levels were measured in the 6 patients in group II. Before angioplasty the mean (+/- SEM) serotonin concentrations were 1.2 +/- 0.2, 1.2 +/- 0.4, and 1.2 +/- 0.3 ng/mL in all cases, group I, and group II, respectively. After angioplasty these values changed to 1.7 +/- 0.4 (P =.0750), 1.2 +/- 0.4 (P =.8001), and 2.1 +/- 0.6 ng/mL (P =.0529), respectively. In group I urinary 5-hydroxyindoleacetic acid concentrations 24 hours before and 24 hours after the procedures were 0.0026 +/- 0.0004 and 0.0031 +/- 0.0006 mg/mg creatinine, respectively (P =.2566). In group II the soluble P-selectin levels significantly increased after intervention, from 26.0 +/- 5.7 to 33.9 +/- 5.3 ng/mL (P =.0296). Although the serotonin levels did not change significantly, the soluble P-selectin levels increased significantly after intervention. Leukocyte activation may therefore contribute to the progression of restenosis after peripheral endovascular therapy.

Prognostic Value of Heart Rate Variability Analysis in Patients with Carcinoid Syndrome

Background/Aims: Recently, a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome. The prognostic relevance of this finding, however, was not clear. Patients and Methods: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 ± 11 years), all of them suffering from metastatic carcinoid tumors, were followed prospectively at our institution. Digital 24-hour Holter monitoring, echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid (5-HIAA) samplings were performed in all study patients at baseline. Indices of time domain heart rate variability obtained from Holter recordings included the standard deviation of all normal RR intervals (SDNN) representing overall variability, the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms (pNN50), both indices reflecting predominantly vagal influences on heart rate. Results: During a mean follow-up of 18 ± 7 months, 15 of 35 patients with carcinoid syndrome (43%) died. Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement (p = 0.09). Patients with the combination of decreased heart rate variability (SDNN <100 ms) and presence of carcinoid heart disease had a significant worse prognosis (p = 0.04) compared to patients without carcinoid heart disease and preserved heart rate variability (SDNN ≧100 ms). Conclusions: The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome.

Discriminating Capacity of Indole Markers in the Diagnosis of Carcinoid Tumors

We evaluated the discriminating capacity of the indole markers urinary 5-hydroxyindoleacetic acid (5-HIAA), urinary serotonin, and platelet serotonin in the diagnosis of carcinoid tumors. Indole markers were measured in 688 patients with suspected carcinoid disease. The initial values of indole markers from patients in whom a carcinoid tumor was confirmed during follow-up (n = 98) were used for ROC analysis. Two groups served as reference populations. The first consisted of 45 healthy individuals ("healthy controls"). The second was a random sample of 40 patients, drawn from the 590 (688 minus 98) patients with carcinoid-like symptoms but without a carcinoid tumor ("clinically suspected patients"). ROC curve analysis showed platelet serotonin to have the highest discriminating capacity, especially in foregut carcinoids. Cutoff values for platelet serotonin obtained from ROC analysis with healthy controls as reference group (5.4 nmol/10(9) platelets) gave a sensitivity of 74%, specificity of 91%, positive predictive value of 63%, and negative predictive value of 95% when applied to the initial 688 patients. Using the cutoff value with the clinically suspected patients as the reference group (9.3 nmol/10(9) platelets) gave a sensitivity of 63%, specificity of 99%, positive predictive value of 89%, and negative predictive value of 93%. Indole markers were increased in 169 (25%) of 688 patients. In 76 (45%) of these 169 patients, a carcinoid tumor was present. Slight increases of markers were associated with non-carcinoid neuroendocrine tumors, non-neuroendocrine tumors, and disturbed bowel motility. ROC curve analysis shows that platelet serotonin is the most discriminating indole marker for the diagnosis of carcinoid tumors. Platelet serotonin especially improves the diagnosis of carcinoids producing small amounts of serotonin.

Acetaminophen inhibits liver tryptophan-2,3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindole acetic acid

The effect of the analgesic agent, acetaminophen was determined on rat forebrain serotonin levels as well as hepatic tryptophan-2,3-dioxygenase (TDO) activity and urinary 5-hydroxyindole acetic acid (5-HIAA). The results show that acetaminophen administration (100mg/kg) over three hours does not affect the holoenzyme of tryptophan-2,3-dioxygenase but significantly inhibits the apoenzyme. This inhibition is accompanied by a concomitant rise in forebrain serotonin levels. This phenomenon is also accompanied by a reduction in urinary 5-HIAA levels. These results suggest that acetaminophen use is accompanied by changes in brain serotonin levels due to inhibition of hepatic tryptophan-2,3-dioxygenase activity. This in turn could explain the possible abuse potential of acetaminophen and its effects on mood at high doses.

Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR.

Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days. To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours. A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months). In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed. Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.

Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians

The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16–75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16–30, 31–45,46–60 and 61–75 years of age, comprising 20, 20,15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.

Foregut carcinoids: a clinical and biochemical analysis.

Gastrointestinal foregut carcinoids make up a small percentage (3% to 6%) of all reported carcinoids. Because these tumors are so uncommon, comparisons between the subtypes have been difficult. The goal of this study was to compare the hormonal and clinical characteristics of gastric, duodenal, and pancreatic carcinoids. A prospective database of approximately 750 carcinoid patients seen by one author over 25 years was reviewed, and the 104 patients with gastric (33), duodenal (17), or pancreatic (54) carcinoids were selected as the subgroup for analysis. These patients were compared with regard to hormone levels, clinical course, treatment, and survival. Duodenal carcinoids exhibited significantly lower serotoninergic hormone levels than did the gastric and pancreatic carcinoids (urine 5-hydroxyindoleacetic acid [mg/24 h], 5 +/- 1 vs 16 +/- 5 and 47 +/- 12, respectively, P = .03). Pancreatic carcinoids presented with more advanced stage (distant metastases 87% vs 42% and 20% for gastric and duodenal, respectively) and had worse outcomes than patients with gastric and duodenal tumors with 10-year survivals of 10%, 59%, and 58%, respectively (P = .003). Pancreatic carcinoids produce higher levels of serotoninergic hormones and have a significantly higher stage and worse outcome than other foregut carcinoids. This study demonstrates that the organ of origin is an important determinant of hormonal activity and clinical course for patients with foregut carcinoids.

Carcinoid Syndrome Caused by an Atypical Carcinoid of the Uterine Cervix

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient’s liver lesions and original cervical lesion (“adenocarcinoma”) suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.

Carcinoid syndrome in the absence of hepatic metastases: correlation of CT and In-111 octreotide imaging

A 49-year-old man was hospitalized for investigation of a 2-year history of flushing and diarrhea. His urinary 5-hydroxyindoleacetic acid level was elevated. CT scanning showed no evidence of hepatic metastases and equivocal masses in the mesentery and right pelvis. In-111 octreotide imaging confirmed focal increased uptake in the midabdomen, right iliac fossa, and lower right pelvis at 24 and 48 hours. At laparotomy, soft tissue masses were resected from the mesentery, lower right pelvis, and small bowel in the right iliac fossa. One of the tumor masses was contained within a Meckel’s diverticulum in the terminal ileum. No liver abnormality was found. All resected masses showed classical carcinoid histologic signs. Symptoms resolved immediately after surgery. FIGURE 1Fig. 1: A CT image at the level of the umbilicus shows an equivocal soft tissue mass within the mesentery. This could easily be mistaken for an unopacified loop of the small bowel.FIGURE 2Fig. 2: A CT image of the pelvis shows a possible soft tissue mass (arrowhead) just medial to the opacified distal right ureter.FIGURE 3Fig. 3: An In-111 octreotide scan at 24 hours shows normal uptake in the liver and spleen. Abnormal uptake is present in the midabdomen, corresponding to the mesenteric soft tissue mass on seen on the CT.FIGURE 4Fig. 4: (A) An In-111 octreotide scan at 24 hours shows additional foci in the right iliac fossa and adjacent to the right superolateral wall of the bladder. (B) A CT scan shows no abnormality of the terminal ileum.

Ultra-High-Dose Lanreotide Treatment in Patients with Metastatic Neuroendocrine Gastroenteropancreatic Tumors

Background: Symptomatic control and occasionally even tumor regression of functional neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) system can be achieved by somatostatin analogues. Assuming a dose-dependent antiproliferative effect of somatostatin analogues, we performed a study with the somatostatin analogue lanreotide in ultra-high dosages in patients with progressive, metastatic GEP NET. Patients and Methods: 30 patients with metastatic GEP NET, progressive during treatment with somatostatin analogues (≤1.5 mg/day) and/or interferon-α, underwent ultra-high-dose lanreotide therapy (5 mg lanreotide s.c. three times a day). Tumor growth was evaluated every 3 months. Serum chromogranin A, serum serotonin as well as urinary 5-hydroxyindoleacetic acetic acid levels were also determined at 3-month intervals. In patients with functional tumors, tumor-related symptoms were documented. Results: After a 1-year treatment period with ultra-high-dose lanreotide, 1 complete and 1 partial remission were observed in patients with functional midgut NET. Eleven patients had stable disease and 11 patients showed continuing tumor growth after 3–12 months of treatment. Symptoms decreased significantly during therapy. Conclusions: Our data show that ultra-high-dose lanreotide treatment in patients with metastatic GEP NET can lead to control of both symptoms and proliferation in at least some patients refractory to conventional therapies.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion before and during cisplatin chemotherapy in patients with intrathoracic malignancy

Background : Nausea and vomiting associated with chemotherapy are common side effects which remain difficult to control. Acute phase nausea and vomiting (0-24 hours after induction of chemotherapy) parallels plasma serotonin release, which explains the effectiveness of receptor antagonists. Serotonin released from gastrointestinal enterochromaffin cells may mediate chemotherapy-induced emesis. In this study, we analyzed urinary excretion of 5-HIAA, the main metabolite of serotonin. Methods : Eight men and four women were studied in their cisplatin chemotherapy cycle. Urinary 5-hydroxyindoleaoetic aicd (HIAA) levels were determined before and during a 24-hour period under ondansetron prophylaxis. Results : Urinary 5-HIAA excretion for a 24-hour period was increased in all patients after induction of cisplatin (P=0.002). Conclusion : Cisplatin chemotherapy is associated with serotonin release in the acute phase. Our finding may provide evidence for a relationship between emesis and serotonin following cisplatin chemotherapy.

Screening for multiple endocrine neoplasia type 1 and hormonal production in apparently sporadic neuroendocrine tumors.

Screening was performed in 130 consecutive patients with apparently sporadic neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) and hormonal production. Screening for MEN1 included measurement of serum calcium and PTH [PTH-(1-84)], gastrin, PRL, and insulin-like growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in patients with two components of the MEN1 syndrome. Screening for hormonal production included measurement of serum neuron-specific enolase (NSE), calcitonin (CT), glycoprotein alpha-subunit (GP alpha), hCG beta-subunit (free hCG beta), and somatostatin levels. Twenty-four-hour urinary free cortisol (UFC) and 5-hydroxyindolacetic acid (5-HIAA) determinations were also performed. Four patients had hyperparathyroidism, none of whom had pituitary or familial disease. Hyperprolactinemia was compatible with a pituitary disease in one patient. No acromegalic feature or any increase in IGF-I was found. Hypergastrinemia, compatible with an associated pancreatic NET, was found in one patient. Genetic screening of the MEN1 gene was performed in five of the six patients with two components of the MEN1 syndrome. A nonsense mutation (Arg108stop) was identified in the tumor of one patient. Elevated NSE, 5-HIAA, CT, GP alpha, free hCG beta, SMS, and nonsuppressible UFC were found in 47%, 46%, 14%, 19%, 12%, 3%, and 6% of NET patients, respectively. Production of CT, GP alpha, and free hCG beta was highly related to the primary site: all but two of these secretions originated in foregut NET. 5-HIAA secretion was found in 27% of foregut-derived and 85% of midgut-derived NET. In conclusion, MEN1 is a rare event in patients presenting with apparently sporadic NET. It occurred mainly in foregut NET and should be screened for by serum calcium and PTH-(1-84) measurements. Routine hormonal measurements should depend on the primary site. NSE, 5-HIAA, CT, and alphaGP should be routinely measured in foregut-derived NET; only serum NSE and 5-HIAA measurements are recommended in midgut-derived NET.

Carcinoids of unknown origin: Comparative analysis with foregut, midgut, and hindgut carcinoids

Background: Carcinoids are rare neuroendocrine tumors typically arising in the gastrointestinal tract. A significant percentage of these tumors present as metastatic disease of unknown primary site. The aim of this study was to better define the functional and clinical characteristics of carcinoids of unknown primary (CUP) site. Methods: This study examines the hormonal activity, clinical characteristics, and survival of 434 patients with carcinoids originating in the foregut, midgut, hindgut, or unknown location. The 143 patients with CUP were compared with the other groups with regard to presenting characteristics, diagnostic tests and therapeutic modalities used, hormonal activity, and survival. Results: The hormone levels (urinary 5-hydroxyindoleacetic acid and serotonin, serum and platelet serotonin) of CUP were not significantly different from midgut carcinoids with metastatic disease. Although survival with CUP was shorter than with carcinoids with identified primaries (10-year survivals of 22% vs 62%, 50%, and 48% for foregut, midgut, and hindgut, respectively), the survival curve for CUP was quite similar to that of patients with midgut carcinoids with distant disease (10-year survival of 22% vs 28%). Conclusions: CUP are similar to midgut carcinoids presenting with metastatic disease with regard to hormone production and survival. Like other carcinoids, CUP can be an indolent disease process with gradual progression over decades. (Surgery 1998;124:1063-70.)