52 POROČILO O PRIMERU / CASE REPORT ACTA MEDICO–BIOTECHNICA 2024; 17 (1): 52-56 Članek prispel / Received 17. 1. 2024 Članek sprejet / Accepted 21. 5. 2024 Abstract This case report highlights the rare oc- currence of acute pancreatitis in a pa- tient exhibiting normal lipase levels. The patient presented to the emergen- cy department with abdominal pain and fever. Laboratory tests indicated an acute inflammatory process but a negative lipase value. The diagnosis was established by a CT scan show- ing necrotizing pancreatic changes with elevated carbohydrate-deficient transferrin (CDT) levels, suggesting alcohol as the etiology. Management involved supportive care, aggressive fluid resuscitation, nutritional sup - port, and empirical antibiotic thera- py, which led to clinical improvement. This case emphasizes the importance of a comprehensive clinical assessment beyond standard biochemical markers in diagnosing and managing pancre- atitis. Izvleček Članek obravnava redek primer pa- cienta z akutnim pankreatitisom ter normalnimi vrednostmi lipaze. Pacient je v urgentni center prišel zaradi bolečin v trebuhu ter povišane telesne tempera- ture. Laboratorijske preiskave so po- kazale akutni vnetni proces, vrednosti lipaze pa so bile normalne. Diagnoza akutnega pankreatitisa je bila postavl- jena s pomočjo CT preiskave abdom- na, najverjetneje alkoholne etiologije zaradi povišanih vrednosti transferina z zmanjšanim deležem ogljikovih hidra- tov (CDT) pri pacientu. Zdravljenje je bilo konzervativno, z agresivnim nadomeščanjem tekočin, prehransko podporo ter empirično antibiotično terapijo, kar je vodilo v klinično izbol - jšanje. Primer poudarja pomembnost celovitega diagnostičnega pristopa pri obravnavi pacientov s pankreatitisom, ki presega le standardne biokemične označevalce. Ključne besede: pankreatitis, negativne vrednosti lipaze, alkoholizem, nekrozantni pankreatitis, konzervativno zdravljenje Key words: pancreatitis, negative lipase, alcoholism, necrotizing pancreatitis, supportive care Akutni pankreatitis z normalnimi vrednostmi lipaze: prikaz primera Acute pancreatitis in a patient with normal lipase: a case report Avtor / Author Tjaša Kitanovski 1,2 , Andrej Grahek 1 , Žan Garvas 3 Ustanova / Institute 1 Splošna bolnišnica Novo mesto, Urgentni center, Novo mesto, Slovenija; 2 Univerzitetni klinični center Ljubljana, Klinični inštitut za radiologijo, Ljubljana, Slovenija; 3 Univerza v Ljubljani, Medicinska fakulteta, Ljubljana, Slovenija; 1 General Hospital Novo mesto, Emergency center, Novo mesto, Slovenia; 2 University medical centre Ljubljana, Institute of Radiology, Ljubljana, Slovenia; 3 University of Ljubljana, Medical faculty, Ljubljana, Slovenia; Naslov za dopisovanje / Correspondence Tjaša Kitanovski General Hospital Novo mesto, Emergency center, Novo mesto, Slovenia tjasa.kitanovski@gmail.com https:/ /doi.org/10.18690/actabiomed.268, CC BY 4.0 © 2024 Avtor(ji) / The Author(s) 53 POROČILO O PRIMERU / CASE REPORT ACTA MEDICO–BIOTECHNICA 2024; 17 (1): 52-56 POROČILO O PRIMERU / CASE REPORT INTRODUCTION Pancreatitis, an inflammatory condition affecting the pancreas, ranges from mild and self-contained to severe and life-threatening cases. Acute pancreatitis, caused predominantly by gallstones and excessive alcohol consumption, remains a significant health concern worldwide despite advancements in medical technology and interventions (1). A diagnosis typically follows the Revised Atlanta Classification, which consists of abdominal pain, elevated serum amylase and/or lipase levels, or imaging demonstrating acute pancreatitis (2, 3). Due to the high negative predictive value of serum lipase (94% to 100%), normal lipase levels during acute pancreatitis are rare (4, 5). A subset of patients may present with normal lipase levels Figure 1. Axial CT scan of the abdomen with IV contrast in the arterial phase shows necrotic pancreatic changes, confirming the diagnosis of acute pancreatitis in a patient with normal lipase levels. Source: Department of Radiology, Novo mesto General Hospital, Novo mesto, Slovenia. 2023 54 POROČILO O PRIMERU / CASE REPORT POROČILO O PRIMERU / CASE REPORT ACTA MEDICO–BIOTECHNICA 2024; 17 (1): 52-56 despite classic signs of pancreatitis, as presented in our case (3, 4). CASE PRESENT A TION A 52-year-old male with a past medical history of arterial hypertension and a childhood history of acute lymphoblastic leukemia presented with a 2-day history of fever and stabbing pain in the left lower quadrant of his abdomen. The patient described the pain as sharp, rated 8/10 in intensity while walking, and alleviated during rest. He denied nausea, vomiting, changes in stool color, or urinary symptoms. The absence of typical symptoms initially prompted consideration of differential diagnoses distinct from pancreatitis. The clinical examination showed mild distress due to abdominal pain. However, the patient was otherwise alert and oriented with stable vital signs. His abdomen was tender to palpation, with muscle guarding present. Peristalsis was present. Laboratory investigations revealed marked leukocytosis, elevated C-reactive protein (CRP) levels, and other laboratory abnormalities consistent with an acute inflammatory process. Notably, the patient’s serum lipase levels were within the normal range (1,11 ukat/L) and did not rise during hospitalization (0,53 ukat/L on day 3) (Table 1). A CT scan of the abdomen with IV contrast showed acute necrotizing pancreatitis, establishing the diagnosis (Figure 1). The patient received aggressive fluid resuscitation, bowel rest, and parenteral nutrition, followed by a targeted diet protocol. The etiology of the pancreatitis was attributed to alcohol due to the elevated CDT levels and concurrent withdrawal symptoms necessitating anxiolytics. Other common etiologies were deemed less probable due to the absence of trauma, medication, and prior interventions. Bilirubin values, liver function tests, triglyceride, and calcium values were normal, and there were no biliary stones on the CT scan. Empirical antibiotic therapy with piperacillin/ tazobactam was initiated due to elevated inflammatory markers and fever. This led to clinical improvement. Table 1: The patient’s laboratory values at admission showed normal lipase and amylase levels. Patient's laboratory values at admission Normal laboratory values Leukocytes 25,64 10^9^/L 4,0 - 10,0 10^9^/L Erythrocytes 5,35 10^12^/L 4,50 - 5,50 10^12^/L Hemoglobin 160 g/L 130 – 170 g/L Thrombocytes 313 10^9^/L 150 - 410 10^9^/L Glucose 5,6 mmol/L 3,6 - 6,1 mmol/L AST (GOT) 0,46 ukat/L < 0,58 ukat/L ALT (GPT) 0,24 ukat/L < 0,74 ukat/L Gamma GT 0,32 ukat/L < 0,92 ukat/L Alkaline phosphatase 1,57 ukat/L < 2,15 ukat/L Lipase 1,11 ukat/L 0 - 1 ukat/L Amylase 0,48 ukat/L 0 - 1,67 ukat/L CRP 387,6 mg/L < 5 mg/L Bilirubin (total) 11 umol/L 3 – 22 umol/L Bilirubin (direct) 7 umol/L 0 - 7 umol/L Triglycerides 0,94 mmol/L 0,6 - 1,7 mmol/L Calcium 1,78 mmol/L 2,1 - 2,6 mmol/L Ethanol 0,5 % CDT 2,71 % 0 - 2,5 % Legend: CRP = C-reactive protein, CDT = carbohydrase-deficient transferrin. Source: Emergency Center, Novo mesto General Hospital, Novo mesto, Slovenia. 2023. The patient was discharged on the tenth day of hospitalization with scheduled follow-up appointments. DISCUSSION The sensitivity of lipase in detecting acute pancreatitis ranges up to 100%. Normal lipase levels are more likely at the early or later stages of the condition. Levels rise within 3 to 6 hours of the onset of acute pancreatitis, peak within 24 hours, and may stay elevated for up to 2 weeks (5, 6). Normal lipase levels in acute pancreatitis can be explained by various factors, including the timing of 55 POROČILO O PRIMERU / CASE REPORT POROČILO O PRIMERU / CASE REPORT ACTA MEDICO–BIOTECHNICA 2024; 17 (1): 52-56 lipase measurement, the degree of pancreatic injury, and individual variations (7-12). Alcoholic pancreatitis, as suspected in our patient, typically presents with elevated lipase levels due to pancreatic inflammation and cellular injury caused by chronic alcohol consumption. This process involves disruption of cellular membranes, impairment of mitochondrial function, and promotion of calcium signaling abnormalities, all contributing to pancreatic cell damage and dysfunction (1, 7). In cases of acute alcoholic pancreatitis, pre-existing chronic damage to the pancreas, such as fibrosis and acinar cell loss, can further complicate enzyme release, resulting in normal lipase levels despite ongoing inflammation (1, 7). This theory is less likely based on our patient’s clinical and radiographic findings, which did not indicate chronic pancreatic changes. Another explanation is that during the early stages of the disease, serum lipase levels may not accurately reflect ongoing pancreatic injury before significant acinar destruction occurs (8, 9). However, lipase levels measured later in the disease course or during periods of lower pancreatic enzyme activity may appear normal or minimally elevated (5, 10). The first theory was deemed unlikely because the patient did not experience a rise in lipase during hospitalization. Still, the latter could have been the case in our patient, where the peak lipase elevation was missed. In some cases, particularly in patients with severe necrotizing pancreatitis, serum lipase levels might paradoxically remain within the normal range despite significant pancreatic damage (11, 12). Additionally, while hypertriglyceridemia can cause normal lipase levels in acute pancreatitis cases, this theory was unlikely in our patient, as he had normal triglyceride levels (9). Despite our patient’s normal lipase levels, his clinical symptoms, elevated inflammatory markers, and imaging evidence consistent with pancreatitis supported the diagnosis (1, 9, 13). His lipase levels remained low during hospitalization, consistent with literature reports and recommendations that serially trending enzymes have no clinical utility. If clinical suspicion is high and abdominal imaging shows signs of acute pancreatitis, it should be treated as such (10). CONCLUSION This case highlights the diagnostic challenge of lipase- negative pancreatitis. Despite normal lipase levels, the patient’s clinical presentation and imaging supported the diagnosis of acute pancreatitis. A comprehensive assessment integrating clinical, laboratory, and imaging data is crucial for accurately diagnosing and managing patients with abdominal pain. 56 POROČILO O PRIMERU / CASE REPORT POROČILO O PRIMERU / CASE REPORT ACTA MEDICO–BIOTECHNICA 2024; 17 (1): 52-56 REFERENCES 1. Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, et al. Acute Pancreatitis: Diagnosis and Treatment. Drugs. 2022;82(12):1251-76. 2. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the At- lanta classification and definitions by inter- national consensus. Gut. 2013;62(1):102-11. 3. Wang YY, Qian ZY, Jin WW, Chen K, Xu XD, Mou YP , et al. Acute pancreatitis with abdom- inal bloating and distension, normal lipase, and amylase: A case report. Medicine (Balti- more). 2019;98(15):e15138. 4. Shah AM, Eddi R, Kothari ST, Maksoud C, Di- Giacomo WS, Baddoura W. Acute pancreati- tis with normal serum lipase: a case series. JOP . 2010;11(4):369-72. 5. Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Bio- chem. 2017;50(18):1275-80. 6. Shahbazi M, Qudsiya Z, Fahel A, Amini A, Ta- noli T. First Reported Case of Dulaglutide-In- duced Acute Pancreatitis With Normal Serum Lipase Level. Cureus. 2023;15(6):e40576. 7. Apte MV, Pirola RC, Wilson JS. Mechanisms of alcoholic pancreatitis. J Gastroenterol Hepa- tol. 2010;25(12):1816-26. 8. Singh A, Shrestha M, Anand C. Acute pancre- atitis with normal amylase and lipase--an ED dilemma. Am J Emerg Med. 2016;34(5):940 e5-7. 9. Nadhem O, Salh O. Acute Pancreatitis: An Atypical Presentation. Case Rep Gastroen- terol. 2017;11(2):359-63. 10. Agrawal A, Parikh M, Thella K, Jasdanwala S. Acute pancreatitis with normal lipase and amylase: an ED dilemma. Am J Emerg Med. 2016;34(11):2254 e3- e6. 11. Sudarsanam H, Ethiraj D, Govarthanan NK, Kalyanasundaram S, Chitra SA, Mohan S. COVID-19 Associated Acute Necrotizing Pan- creatitis with Normal Serum Amylase and Lipase Levels: Report of an Unusual Finding. Oman Med J. 2021;36(5):e304. 12. Lankisch PG, Burchard-Reckert S, Lehnick D. Underestimation of acute pancreatitis: pa- tients with only a small increase in amylase/ lipase levels can also have or develop severe acute pancreatitis. Gut. 1999;44(4):542-4. 13. Mathur AK, Whitaker A, Kolli H, Nguyen T. Acute pancreatitis with normal serum lipase and amylase: a rare presentation. J Pancreas (Online) 2016 Jan;17(1):98-101. 14. Lankisch PG, Apte M, Banks PA. Acute pan- creatitis. Lancet. 2015;386(9988):85-96.