Endocrine Abstracts

Background: Approximately 20% of NET patients develop CS, characterised by diarrhoea and flushing. However, CS is not the only cause of diarrhoea among NET patients. Non-CS causes should be considered to allow for appropriate management. We investigated the reported occurrence of diarrhoea from various non-CS causes in patients with gastroenteropancreatic NETs (GEP-NETs), to explore the need for differential diagnosis (DDx) of NET diarrhoea.

Methods: MEDLINE/Embase/Cochrane Library were searched in September 2018 with terms for NETs, CS and diarrhoea. Congress abstract books/bibliographies/ClinicalTrials.gov were hand-searched. Two independent reviewers screened articles at title/abstract and full text stage. Articles reporting evidence on potential causes of diarrhoea in GEP-NET patients were included.

Results: 19 articles reported on non-CS causes of diarrhoea. 14 reported on pancreatic enzyme insufficiency (PEI) in NET patients, predominantly on/after treatment with somatostatin analogs (SSAs); 17.3%–84% of patients experienced steatorrhoea, and where reported, 14.3%–46.1% of NET patients received pancreatic enzyme replacement therapy. Faecal fat measurement confirmed PEI in 11.6% of patients on SSAs, and faecal elastase test was used to explore PEI in 3 further studies. Variation in reported proportions could result from heterogeneity in study design and patient population. Small intestinal bacterial overgrowth (SIBO) diagnosed by hydrogen and methane breath test was reported in 23.6%–62% of NET patients; bile acid malabsorption (BAM) in 80% by SeHCAT scan. Single cases of colitis (20%) and Campylobacter coli infection (7.1%) were reported in 2 studies of patients with CS diarrhoea. While conditions such as PEI were reported, most cases were not confirmed with clinical tests, or it was not clear if they were truly causing diarrhoea instead of, or in addition to, CS. Additional studies suggested other potential causes of diarrhoea without quantitative data, including short bowel syndrome, chemotherapy-associated diarrhoea, dumping syndrome, laxative abuse and lymphangiectasia.

Conclusions: Quantitative evidence on prevalence of diarrhoea of different aetiologies in NET patients is lacking. PEI was most commonly reported, suggesting that it is important to consider in DDx of NET diarrhoea. Limited data on BAM, SIBO and infection, and lack of data on other potential causes of diarrhoea, could result from little awareness among clinicians or lack of investigation into these causes; management of diarrhoea in NET patients should involve experienced clinicians e.g. gastroenterologists and surgeons. Further research is required to determine the prevalence of each cause, to inform and highlight the importance of DDx of diarrhoea in NET patients.