Hypercalcemia-Induced Pancreatitis in Pregnancy Following Calcium Carbonate Ingestion

Introduction

Acute pancreatitis is rare in pregnancy, occurring in approximately 3 in 10 000 pregnancies. ¹ The most common identified causes of acute pancreatitis in pregnancy are gallstones and alcohol abuse, which is similar to that of the general population. ² A much less common cause of pancreatitis is hypercalcemia. Proposed mechanisms include thickening of protein plugs in pancreatic ducts by the formation of pancreatic calculi and calcium activation of intrapancreatic trypsinogen. ^3,4 In one study, calcium infusions in rats induced acute hyperamylasemia and early ectopic trypsinogen activation, as well as dose-dependent morphological alterations characteristic of acute pancreatitis. ⁴ This supports the pathophysiological relevance of excess calcium and offers a possible mechanism for its association with clinical pancreatitis. In this report, the authors describe a pregnant patient who developed hypercalcemia and pancreatitis after ingesting an unquantifiable amount of calcium carbonate for Gastroesophageal Reflux Disease (GERD).

Case Presentation

A 31-year-old Caucasian pregnant female (gravida 3, para 1) presented to the emergency department at 34 weeks’ gestation with a one day history of right upper quadrant abdominal pain, nausea, and vomiting. She had an uncomplicated pregnancy up until this point, and her medical history included migraines, postpartum depression, and GERD. The patient’s home medications included 1 prenatal multivitamin orally daily (prenatal 1) and calcium carbonate 500 mg orally in an unquantifiable amount due to constant consumption. She denied alcohol, tobacco, and illicit substance usage. Laboratory findings upon presentation included potassium 2.6 mmol/L, chloride 100 mmol/L, carbon dioxide 26 mmol/L, calcium 15.6 mg/dL (corrected calcium 16.6 mg/dL with albumin 2.7 g/dL), magnesium 0.7 mg/dL, phosphorus 1.8 mg/dL, serum creatinine 1.14 mg/dL, triglyceride 885 mg/dL, serum amylase 370 U/L (RR: 25-115 U/L), serum lipase 4712 U/L (73-393 U/L), parathyroid hormone 18.7 pg/mL (RR: 13.8-85 pg/mL), thyroid stimulating hormone 0.275 μIU/mL (RR: 0.358-3.740 μIU/mL), total bilirubin 0.3 mg/dL (RR: 0.2-1 mg/dL), AST 16 U/L (RR: 15-37 U/L), ALT 16 U/L (RR: 13-56 U/L). An abdominal ultrasound on the day of admission revealed mild nonspecific dilatation of the right renal collecting system but an otherwise negative examination, excluding obstructive pancreatitis. The patient was made nothing by mouth (NPO), and aggressive hydration was initiated. Potassium replacement was given with intravenous potassium phosphate and oral potassium chloride. Despite 4 L of fluid resuscitation, the patient’s lipase rose to 8370 U/L and serum creatinine rose to 1.43 mg/dL on hospital day 2, and the decision was made to perform an emergency cesarean section. A 2320-g boy was delivered (Apgar score 8 at 1 minute, 9 at 5 minutes). Within hours after delivery, her epigastric pain and nausea had resolved. The day following delivery, her triglyceride level had improved to 212 mg/dL and her serum lipase had improved to 1880 U/L. Upon further discussion, the patient admitted to taking calcium carbonate “constantly” for the past several weeks for the treatment of perceived reflux symptoms. Her actual consumption amount was unquantifiable, likely causing her hypercalcemia. The patient’s hypercalcemia was managed by administration of intravenous D5 ½ NS initially and was then changed to Lactated Ringer's solution and her corrected calcium level improved to 11.9 mg/dL within 24 hours. She developed some paresthesias on hospital day 4. Laboratory studies revealed hypocalcemia (corrected calcium 7.2mg/dL), for which she received 2 g of intravenous calcium gluconate. She was discharged home on hospital day 5.

Discussion

This case report describes hypercalcemia-induced pancreatitis in a pregnant patient following excessive calcium carbonate ingestion over a period of several weeks for GERD. Our literature search revealed previous reports of milk–alkali syndrome (MAS) in pregnant patients from calcium carbonate ingestion but only 2 cases of MAS and resultant pancreatitis in pregnant patients. ^5,6 MAS is typically described as the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis that results from the ingestion of large amounts of calcium-containing products. In this particular case, however, serum bicarbonate was not ever elevated. Ongoing metabolic acidosis from acute pancreatitis may have blunted the elevated bicarbonate that you would usually see with MAS.

In this case, fluid resuscitation and delivery of the fetus facilitated triglyceride and calcium lowering and resolution of the pancreatitis. It should be noted that intravenous fluid selection was changed from D5 ½ NS to Lactated Ringer's solution on hospital day 2 as part of the hospital’s intrapartum protocol, which would not be the preferred fluid in a patient with hypercalcemia due to a small but notable calcium content of 3 mEq/L. We concluded that the subsequent hypocalcemia the patient developed was due to a suppressed parathyroid gland from previous hypercalcemia in combination with the calcium-lowering effect of the delivery of the infant and the oxytocin received after surgery. Subsequent symptomatic hypocalcemia was also noted in a previous report but was attributed to the administration of pamidronate, parathyroid hormone suppression, and possibly the calcium sequestration and fat saponification associated with the pancreatitis. ⁶

According to the Naranjo nomogram, pancreatitis from calcium carbonate ingestion in this patient case was considered probable with a score of 5. ⁷ Although we have attributed the pancreatitis to hypercalcemia, it should be noted that the patient did have mildly elevated triglycerides, 885 mg/dL on the day of admission (nonfasting) and 743 mg/dL on hospital day 2. Triglyceride levels gradually increase during pregnancy with up to a 4-fold increase in the third trimester, but hypertriglyceridemia is not considered a risk factor for the development of pancreatitis unless plasma triglyceride levels are >1000 mg/dL. ² Pregnancy has also been independently associated with pancreatitis. ⁸

Our patient’s consumption of calcium carbonate for GERD led to hypercalcemia and likely precipitated acute pancreatitis. Fluid resuscitation and delivery of the fetus facilitated triglyceride and calcium lowering and resolution of the pancreatitis. This case substantiates the potential harm of using large doses of calcium carbonate, a medication frequently consumed in the pregnant population. Education to patients about over-the-counter (OTC) calcium carbonate–containing antacids and the limit of 1.2-1.5 g/d of elemental calcium (3-3.75 g calcium carbonate) is essential in reducing adverse events. ⁹ During pregnancy and lactation, treatment with calcium carbonate should be under the direction of a physician.

Teaching Points

Calcium carbonate is commonly utilized in the pregnant population to relieve GERD due to its OTC status and benign side effect profile.