S3591 Benign Pancreatic Hyperenzymemia: An Uncommon Cause of Elevated Pancreatic Enzymes

Introduction: Serum pancreatic enzyme tests (amylase and lipase) are widely used to assess pancreatic function and to aid in the diagnosis of conditions such as acute or chronic pancreatitis. However, elevated pancreatic enzyme levels can also result from various non-pancreatic conditions. Thus, interpreting isolated enzyme elevation without correlating clinical and imaging findings remains a diagnostic challenge. We present a case of benign pancreatic hyperenzymemia (BPH), also known as Gullo’s syndrome—a rare and benign cause of persistently elevated pancreatic enzymes. Case Description/Methods: A 65-year-old White man with history of hypertension, diverticular disease, and colonic polyps was referred to the gastroenterology clinic for persistently elevated amylase and lipase levels. These tests were initially ordered by his primary care provider in 2018 following his mother was diagnosed with pancreatic cancer. At that time, mild elevations in pancreatic enzymes were observed. Over the following years, repeated testing showed fluctuating yet persistently elevated enzyme levels. Liver function tests remained within normal limits. The patient reported mild bloating only but denied alcohol use. Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRCP) performed in April 2023 revealed hepatic steatosis without biliary ductal dilatation, and pancreatic divisum. Upper endoscopy and colonoscopy performed in 2024 were unremarkable. A follow-up magnetic resonance imaging/MRCP in April 2024 for pancreatic cancer screening showed no significant interval changes. Given the extensive negative work-up—including normal liver function tests, negative imaging, and unremarkable endoscopy—the persistent enzyme elevation in an otherwise asymptomatic patient is most consistent with BPH. Although pancreatic divisum can be associated with pancreatitis, it typically presents with clinical symptoms and higher lipase levels. The concurrent presence of both macroamylasemia and macrolipasemia is unlikely. Discussion: BPH is characterized by chronic, fluctuating elevations of pancreatic enzymes in the absence of pancreatic pathology. The diagnosis is typically made after ruling out other causes and is supported by periodic normalization and fluctuation of enzyme levels over months to years. Although a diagnostic protocol involving daily enzyme measurements over 5 days has been proposed, our patient declined this testing due to needle phobia. Recognizing this benign entity is essential to avoid unnecessary investigations and to provide appropriate reassurance to patients.