Biochemistry Markers of Neuroendocrine Tumours

Neuroendocrine tumours (NET) are a diverse group of neoplasms originating from cells within the diffuse endocrine system. Urine 5-hydroxyindole acetic acid (5-HIAA), a metabolite of serotonin is commonly used in the diagnosis and monitoring of patients with NET in particular small intestinal neuroendocrine tumour with carcinoid syndrome. The collection of urine 5- HIAA over a 24 hour period, and exposure to the acid preservative in the sample container are limitations in the use of urine 5-HIAA. In this thesis, I have developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-HIAA with acceptable analytical performance. I have also demonstrated that it compares well with the currently used urine 5-HIAA assay. I compared plasma and serum 5-HIAA with serotonin, chromogranin A (CgA) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). A significant correlation was observed. Somatostatin analogues (SSA) are often used as first line treatment in patients with metastatic NET. Diarrhoea and steatorrhoea are adverse effects reported with SSA use, which can lead to malabsorption of fat-soluble vitamins (FSV) and trace elements (TE). I have therefore investigated the prevalence of deficiencies in fat-soluble vitamins and trace elements. Deficiencies especially in vitamin K1 and zinc were observed I have shown in this thesis that the measurement of 5-HIAA in plasma or serum is a suitable alternative to urine, and it addresses the inconvenience associated with the timing and collection of the urine. In patients with NET on SSA, monitoring and supplementation of FSV and TE should be considere

An association between post-meal bile acid response and bone resorption in normal subjects

Background The mechanism surrounding bone suppression after a meal may involve several mediators, but is yet to be clarified. Bile acids (BA) function as signalling molecules in response to feeding, and may be directly involved in bone suppression acutely after a meal. The aim of this study was to test the hypothesis that BA are involved in the acute bone suppression observed after a meal. Methods A prospective study in which samples collected from volunteers fed a 400 Kcal test meal after an overnight fast were analysed for parathyroid hormone (PTH), BA, and carboxyterminal of type 1 collagen telopeptide (CTX). The study was carried out in 10 healthy male volunteers. Ethical approval was obtained from the Local Research and Ethics Committee at King's College Hospital. Results Total BA, glycine conjugated bile acids (GCBA), PTH and CTX showed a response to meal ingestion. There was a negative correlation between percentage change in PTH and CTX ( R2 = −0.82, P = 0.004), and between PTH and GCBA ( R2 = −0.39, P = 0.005). Conclusion This study demonstrated an association between GCBA and PTH suppression after a meal. The drop in PTH concentration after a meal may be responsible for the suppression of bone resorption as observed by the decrease in CTX concentration. </jats:sec

The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study

Abstract Background Inflammation is associated with increased bone resorption; the role of inflammation in postprandial bone turnover has not been explored. Consumption of milk fat globule membrane (MFGM) reduces inflammation in animal models. This study aimed to measure postprandial changes in bone turnover after intake of high saturated fat test meals, with- and without the anti-inflammatory ingredient MFGM. Methods Subjects (n = 36 adults) were obese (BMI 30–39.9 kg/m2) or overweight (BMI 25–29.9 kg/m2) with two traits of Metabolic Syndrome. Subjects consumed a different test meal on four occasions at random; blood draws were taken at baseline and 1, 3, and 6 h postprandial. Test meals included whipping cream (WC), WC + MFGM, palm oil (PO) and PO + MFGM. Biomarkers of bone turnover and inflammation were analyzed from all four time points. Results Test meal (treatment) by time interactions were significant for bone resorption marker C-telopeptide of type 1 collagen (CTX) (p < 0.0001) and inflammatory marker interleukin 10 (IL-10) (p = 0.012). Significant differences in overall postprandial response among test meals were found for CTX and soluble intercellular adhesion molecule (sICAM), with the greatest overall postprandial suppression of CTX occurring in meals containing MFGM. However, test meal by MFGM interactions were non- significant for bone and inflammatory markers. Correlations between CTX and inflammatory markers were non-significant. Conclusion This exploratory analysis advances the study of postprandial suppression of bone turnover by demonstrating differing effects of high SFA meals that contained MFGM; however MFGM alone did not directly moderate the difference in postprandial CTX response among test meals in this analysis. These observations may be useful for identifying foods and ingredients which maximize the suppression of bone resorption, and for generating hypotheses to test in future studies examining the role of inflammation in postprandial bone turnover. Trial registration Clinicaltrials.gov NCT01811329 . Registered 11 March 2013