Novel endoscopic and MRI-based methods for evaluating exocrine pancreatic function in pancreatitis and monogenic forms of diabetes

Abstract

Background: Monogenic diabetes (Maturity onset diabetes in the young, MODY) are autosomal dominantly inherited diabetes syndromes characterized by diabetes due to beta cell dysfunction, with typical onset of diabetes before 25 years of age. Two MODY subtypes, HNF1B-MODY and CEL-MODY, have been associated with exocrine pancreatic dysfunction. Assessment of exocrine pancreatic function is a challenge due to few available tests with acceptable feasibility and diagnostic value. Aims: In the present study we wanted to evaluate two novel methods for measuring pancreatic exocrine function; a rapid endoscopic secretin test and a dynamic magnetic resonance imaging (MRI) based protocol. We further wanted to use these two methods to assess the degree and nature of exocrine pancreatic dysfunction in CELMODY and HNF1B-MODY. Materials and methods: We recruited 52 consecutive patients with suspected chronic pancreatitis, 23 patients with CEL-MODY and 8 patients with HNF1B-MODY. Suspected chronic pancreatitis patients underwent the endoscopic procedure only, while MODY patients were offered endoscopy and MRI procedure. In addition, 25 healthy controls underwent endoscopy and 20 healthy controls underwent the MRI protocol. In patients with suspected chronic pancreatitis, a renowned multimodal clinical score was used as reference standard. In MODY patients results from the examinations were compared to nutritional status as achieved from patient records before any treatment with pancreatic enzyme supplements. The endoscopic procedure started 30 minutes after secretin stimulation, with 15 minutes collection of duodenal juice. Duodenal juice was analyzed for bicarbonate in chronic pancreatitis patients, and for bicarbonate and digestive enzyme activities in MODY-patients and healthy controls. The MRI protocol consisted of anatomical imaging, followed by dynamic imaging before and after secretin stimulation. The dynamic series consisted of repeated duodenal fluid volume quantification with magnetic resonance cholangiopancreaticography (MRCP) and measuring apparent diffusion coefficient (ADC) in pancreatic tissue using diffusion-weighted imaging. Results: Using bicarbonate as diagnostic marker, the rapid endoscopic secretin test had acceptable diagnostic value in detecting chronic pancreatitis, and performed significantly better than fecal elastase 1. In healthy controls, increase in secretin stimulated duodenal fluid volumes correlated well with changes in ADC after secretin stimulation. In CEL-MODY patients we found moderately low bicarbonate levels and reduced pancreatic fluid output, and severely reduced digestive enzyme activity levels compared to controls. With exception from low levels of vitamin E, CEL-MODY patients revealed no signs of malnutrition. In HNF1B-MODY patients we found moderately reduced bicarbonate levels, reduced pancreatic fluid output and moderately reduced levels of digestive enzyme activities compared to controls. Pancreatic gland volumes were small in all but one HNF1B-MODY patients, but pancreatic volume output per gland size was increased. Conclusions: Both rapid endoscopic secretin test and the MRI protocol are feasible and well tolerated examination modalities reflecting pancreatic exocrine function. CEL-MODY patients have moderately reduced ductal and severely reduced acinar pancreatic function, but compensated nutritional status. HNF1B-MODY patients have moderately reduced ductal and acinar pancreatic function, partly compensated by hypersecretion from a hypoplastic pancreas.