Thiazide-Induced Acute Interstitial Pancreatitis in a 55-Year-Old Male: A Rare Adverse Drug Reaction.

A 55‐year‐old Asian man visited the outpatient department (OPD) for a routine check‐up on March 10, 2025. He was hypertensive for 5 years for which he was taking losartan 50 mg daily. He was nondiabetic and had a family history of hypertension in his father (85 years) and brother (52 years). He was a nonsmoker, nonalcoholic, and followed a vegetarian diet. He complained of occasional episodes of mild diffuse headache. On examination, his blood pressure was 150/90 mm‐Hg in both arms, and other vital signs were within normal limits. Workup for secondary hypertension was done without significant findings and he was advised to follow lifestyle modifications, including regular exercise and the DASH (Dietary Approaches to Stop Hypertension) diet. He was also asked to maintain a blood pressure record at home for 1 week and return for follow‐up. After 1 week, his home‐recorded blood pressure showed persistent elevation above 150/90 mmHg. A combination antihypertensive therapy — losartan 50 mg with hydrochlorothiazide 25 mg—was prescribed once daily in the evening, and he was advised to continue monitoring his blood pressure and return in 2 weeks. Two weeks later, he presented to the emergency department with severe epigastric pain, nausea, and two episodes of vomiting. The pain was severe and constant, radiating to the back at mid ‐thoracic region. Laboratory tests showed l eukocytosis with neutrophilia, elevated serum amylase and lipase levels with a normal lipid profile (Table  1 ). The pancreas could not be clearly visualized on the abdominal ultrasonogram and showed no gallstones. A contrast‐enhanced CT scan further confirmed the diagnosis of acute interstitial pancreatitis with a bulky pancreas, fuzzy margins, and minimal peripancreatic fluid collection with peripancreatic fat stranding (Figure  1 ). There was no necrosis, thrombosis, and pancreatic duct dilatation. The gallbladder appeared normal, and there was no dilation of the common bile duct (CBD). Laboratory values of patient on day of admission and 2 days after admission. Acute interstitial pancreatitis with bulky pancreas, fuzzy margins, peri‐pancreatic fat stranding, and minimal free fluid. The absence of gallstones on imaging and a normal lipid profile excluded gallstones and hypertriglyceridemia. To verify the patient's claim of no history of alcohol intake, collateral history was taken from the patient's family, which was supported by a normal gamma‐glutamyl transferase (GGT) level of 28 U/L and undetectable blood alcohol concentration on admission. Imaging showed no features suggestive of chronic pancreatitis. These findings collectively helped us to exclude alcohol as an etiological factor in our patient. Autoimmune pancreatitis was excluded based on the absence of other autoimmune disorders, lack of involvement of other organs, and CT findings that were not consistent with the typical findings of autoimmune pancreatitis. Blood cultures obtained at the time of presentation showed no growth after 72 h of incubation, excluding any bacterial infections. The patient resides in a non‐endemic area for scorpions, and there were no physical signs of a scorpion bite in a thorough physical examination. There was no history of recent travels, trauma, or surgical interventions. The patient was managed conservatively with i ntravenous fluids, analgesics, bowel rest (NPO). Hydrochlorothiazide was suspected as the potential cause of the pancreatitis and was discontinued. The patient showed gradual clinical improvement. He was discharged after 5 days of hospital stay with oral medications and advised to follow‐up in 2 weeks for further evaluation in search of etiology. An MRCP (Magnetic Resonance Cholangiopancreatography) was performed and found to be normal, ruling out biliary obstruction or pancreatic duct anomalies. The combination of losartan and hydrochlorothiazide was permanently discontinued, and he was switched to a combination of losartan 50 mg and amlodipine 5 mg.

Kshitiz Pandey: conceptualization, formal analysis, methodology, project administration. Ashish Panday: supervision, writing – original draft. Pratik Pandey: formal analysis, methodology, validation. Anand Chaudhary: project administration, resources, software, writing – review and editing. Sushmita Khanal: data curation, investigation, validation, writing – review and editing.

Thiazide diuretics are the first‐line pharmacologic management of hypertension and are among the commonly prescribed antihypertensives [ 5 , 6 ]. However, rare but serious adverse effects such as acute pancreatitis must be considered when more common etiologies have been ruled out. Our case highlights a case of drug‐induced acute pancreatitis in a patient initiated on thiazide therapy for hypertension. Thiazide diuretics exert their antihypertensive effect by inhibiting sodium‐chloride symporters in the distal convoluted tubule, thereby reducing plasma volume and vascular resistance. Though the exact mechanism is still unclear, thiazide‐induced pancreatitis has been attributed to several potential mechanisms, including drug‐induced hypercalcemia, hypersensitivity reactions, pancreatic duct constriction, and direct cytotoxic effects on acinar cells [ 1 , 7 ]. Diagnosis of acute pancreatitis is classically based on meeting two out of the following three criteria: Characteristic abdominal pain; serum lipase or amylase levels ≥ 3 times the upper limit of normal; and radiologic findings consistent with pancreatic inflammation [ 7 ]. Our patient met all three criterias. Finding the etiology of acute pancreatitis is a challenge when the common etiologies such as gallstones, alcohol use, hypertriglyceridemia, and trauma are excluded. Imaging in our case ruled out gallstone disease and laboratory evaluation did not reveal hyperlipidemia or hypercalcemia. No history of alcohol intake, infection, or prior abdominal trauma prompted the search for the rarer cause of acute pancreatitis. Thus, the recently initiated thiazide diuretic became the prime suspect. Although drug‐induced acute pancreatitis accounts for a small proportion of cases (0.1%–2%), there is a huge list of drugs that has been linked with acute pancreatitis [ 8 ]. Among them, diuretics, mainly loop diuretics and thiazides, have been reported in many literatures [ 1 , 2 , 3 , 4 ]. The European Case–Control Study on Drug‐Induced Acute Pancreatitis (EDIP) did not find a significant association between thiazide diuretic use and an increased risk of acute pancreatitis, suggesting that while the risk exists, it may be modest [ 9 ]. The case–control analysis by Ksiądzyna [ 10 ] showed that patients on diuretics present two and a half times more frequently with AP than the control group. Pravallika et al. [ 11 ] reported eight hydrochlorothiazide‐induced cases out of 31 cases (25.8%) of drug‐induced acute pancreatitis. The latency period between drug initiation and symptom onset may range from days to years, complicating recognition [ 1 ]. Patients at higher risk for developing thiazide‐induced pancreatitis include those with certain demographic and clinical characteristics. According to the analysis of the FDA Adverse Event Reporting System (FAERS), males and individuals aged 41–54 years are at increased risk for drug‐related acute pancreatitis, which includes thiazide diuretics. Additionally, patients with multiple comorbidities, such as hypertension, who are on polypharmacy regimens, may also be at higher risk due to the potential for drug interactions and cumulative adverse effects [ 12 , 13 ]. Various pathophysiological mechanisms for thiazide‐induced pancreatitis have been proposed, including direct damage to pancreatic acinar cells which produce digestive enzymes, immune‐mediated pancreatic injury, pancreatic duct constriction possibly resulting from drug‐induced changes in smooth muscle tone or ductal pressure, and metabolic complications like thiazide‐induced hypercalcemia or hypertriglyceridemia, both are known risk factors for acute pancreatitis [ 1 , 3 , 6 , 7 , 8 , 14 ]. Additionally, thiazides may cause ischemia of the pancreas by inducing hypovolemia and reducing pancreatic blood flow, which can contribute to pancreatic injury [ 13 ]. There is currently no specific genetic predisposition directly linked to the development of thiazide‐induced pancreatitis [ 9 , 15 ]. Checking normal IgG4 levels could help exclude the possibility of acute episodes of autoimmune pancreatitis [ 16 ]. In our case, the patient had a normal lipid profile and calcium levels. Also, the electrolytes level was normal. Normal ductal luminal diameters of the biliary tree excluded pancreatic duct constriction. Thus, a hypersensitivity reaction or direct cytotoxicity is suspected based on laboratory findings and radiographical findings. The cornerstone of initial therapy was aggressive intravenous fluid resuscitation aimed at counteracting third‐space fluid loss, maintaining pancreatic perfusion, and minimizing the risk of necrosis [ 8 , 17 ]. Supportive measures including pain control with opioids and bowel rest were instituted; the suspected causative agent, that is, the thiazide diuretic, was immediately discontinued. Our patient improved clinically within 72 h with marked reduction in the level of pancreatic enzymes and resolution of symptoms. Though there are no exact criteria to confirm a drug caused pancreatitis, clinicians need to consider the temporal association between drug exposure and symptom onset, rule out other possible causes, improvement after stopping the drug, and note if symptoms return when restarting the drug (usually not tested due to ethical concerns). Since thiazide‐related pancreatitis can develop long after starting the drug, it is also crucial to take a detailed medication history in any patient with pancreatitis of unknown cause. For those with ongoing issues like high calcium levels caused by thiazides, stopping the drug might be wise even before pancreatitis develops as a preventive measure.

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Acute pancreatitis is a potentially life‐threatening inflammatory condition of the pancreas with a wide spectrum of clinical presentations. The most common etiologies include gallstones, chronic alcohol consumption, hypertriglyceridemia, certain infections, and idiopathic causes. However, drug‐induced pancreatitis remains a less frequent but important and often under‐recognized cause, accounting for approximately 0.1%–2% of cases [ 1 , 2 , 3 ]. The World Health Organization (WHO) has identified over 500 medications as potential causes of acute pancreatitis as an adverse drug reaction [ 4 ]. Most of the cases of drug‐induced pancreatitis cause mild to moderate pancreatitis and recover with fewer complications following the withdrawal of offending drugs. Among them, thiazide diuretics, widely prescribed for hypertension and heart failure, have been associated in many literatures [ 1 , 2 , 3 ]. Although the exact pathophysiology is still unclear, proposed mechanisms include hypersensitivity reactions, drug‐induced hypercalcemia, and direct pancreatic toxicity [ 1 , 3 ]. This case report highlights the importance of considering thiazide as a potential cause of acute interstitial pancreatitis in a patient with a recent start of intake, when there are no other identifiable etiological factors. The temporal relationship between drug initiation and symptom onset should be considered when diagnosing drug‐induced acute pancreatitis.

The authors declare no conflicts of interest.