S3490 A Rare Link Between Pyridostigmine Therapy and Gallstone Migration in Myasthenia Gravis

Introduction: Gallbladder stones occur due to digestive fluid calcification in gallbladder affecting 10%–15% of the adult U.S. population, with higher prevalence in young females. About 10% of the gallstones migrate to bile duct leading to choledocholithiasis with a cholestatic pattern of liver injury. Pyridostigmine, an acetylcholinesterase inhibitor commonly used to treat myasthenia gravis, increases acetylcholine levels potentially leading to high parasympathetic drive promoting gallbladder motility and contraction. We present a case of an 83-year-old man with myasthenia gravis who developed acute choledocholithiasis, likely triggered by an increased pyridostigmine dose. Case Description/Methods: An 83-year-old man with known history of myasthenia gravis on pyridostigmine, presented with 1-week complaints of fatigue, weakness and watery diarrhea. He was hemodynamically stable on presentation, and his physical examination was unremarkable. Patient reported that his Pyridostigmine dose was increased from 60 mg three times a day (180 mg/day) to 120 mg three times a day (360 mg/day) just before the start of his symptoms. A computed tomography abdomen and pelvis with contrast revealed choledocholithiasis with a 0.8 cm stone in the distal common bile duct, a dilated common bile duct measuring 1.5 cm, and gallstones in the gallbladder. Liver function tests showed ALP 90, ALT 13, AST 24, total bilirubin 0.9, and direct bilirubin 0.4. Patients' watery diarrhea could be attributed to malabsorption with underlying choledocholithiasis or increased pyridostigmine dose. Patient underwent endoscopic retrograde cholangiopancreatography (ERCP) which showed bulging major papilla and filling defect - subsequently stone was retrieved and a covered metal stent was placed. Repeat liver function tests were normalized; the patient subsequently underwent laparoscopic cholecystectomy. Post surgery period was uncomplicated and patient symptoms of diarrhea resolved. Discussion: Pyridostigmine can increase parasympathetic nervous system drive with the stimulation of muscarinic receptors. These receptors are found in the smooth muscles of gallbladder thus pyridostigmine can lead to increased contraction by increasing acetylcholine levels. This can theoretically lead to translocation of stones from gallbladder and cause acute choledocholithiasis. In this case, the rapid onset of choledocholithiasis following a pyridostigmine dose increase highlights a potential parasympathetic-mediated mechanism which has been rarely reported. Thus use of high dose parasympathomimetics should be carefully handled with closed follow up for such rare complications.