Casting a Wider NET: Pancreatic Exocrine Insufficiency Induced by Somatostatin Analogues among Patients with Neuroendocrine Tumours?

SIMPLE SUMMARY: Somatostatin analogues (SSA) are used to treat patients with unresectable neuroendocrine tumours (NET). An underrecognized side-effect of SSAs is pancreatic exocrine insufficiency (PEI), where the pancreas is unable to maintain the normal digestion of food. Whilst the few papers that have investigated SSA-induced PEI report rates of between 12 and 48%, anecdotal evidence of PEI symptoms suggests this figure is greater. The disparity may be due to the overlap in symptoms of the tumour itself and PEI, but also the diagnostic methods used. Swift diagnosis of PEI is essential to ensure appropriate management of the symptoms for an improved survival and quality of life for patients. This study is the first to utilize the (13)C-mixed triglyceride breath test ((13)C-MTGT) in patients before and after they commence SSA treatment, demonstrating a novel and alternative diagnostic strategy in this patient cohort, whilst highlighting the early impact of SSAs on pancreatic function. ABSTRACT: Somatostatin-analogues (SSAs) are a first-line treatment of unresectable neuroendocrine tumours (NETs). However, SSAs inhibit pancreatic secretions, which could lead to pancreatic exocrine insufficiency (PEI). PEI is known to be detrimental to patient quality of life and nutritional status. This study aimed to evaluate the effect of SSAs on pancreatic exocrine function in patients with NETs, using the (13)C-mixed triglyceride breath test ((13)C-MTGT). Exocrine function was assessed using the (13)C-MTGT at baseline and after a third SSA injection (two months). A quotient of (13)CO(2)/(12)CO(2) was measured by mass spectrometry, and the cumulative percent dose recovered at 6 h (cPDR) is reported. The secondary endpoints investigated were change in weight, HbA1C, and vitamin D levels. Ten patients completed the study. Exocrine function reduced in all patients (n = 10) following SSA therapy (median reduction from baseline: −23.4% (range: −42.1–0.5%, p = 0.005)). vitamin D levels decreased in all but one patient (median decrease from baseline: −26.5%, (−44.7–10%; p = 0.038)), and median HbA1C levels increased by 8.0% (0–59.3%; p = 0.008). Change in weight was not significant (median decrease from baseline: −0.21% (−4.5–3.5%, p = 1.000)). SSA therapy has a consistent impact on exocrine function from early in the treatment course, but the long-term clinical effects of this remain to be defined. Further studies are required to determine the clinical relevance of this observation and optimise the management of PEI in this cohort.