P3C246: An Unexpected Cause of Infantile Cholestasis

Introduction: Conjugated hyperbilirubinemia in an infant always requires further work-up. We present a case of a two-month-old female whose presenting symptom of hyperbilirubinemia resulted in a rare, non-hepatic diagnosis.

Case Description: A two-month-old female presented for persistent jaundice. She was born to a mother with gestational diabetes mellitus (GDM) and required neonatal intensive care unit (NICU) care for persistent hypoglycemia, attributed to her mother’s GDM, and hyperbilirubinemia.

After discharge from the NICU, she had persistent failure to thrive and jaundice. An outpatient gastroenterologist obtained labs which noted an elevated direct bilirubin and gamma-glutamyl transferase (GGT). She had an abdominal ultrasound which noted a contracted gallbladder.

Due to her persistent cholestasis, she was admitted to the hospital to rule out biliary atresia. A liver biopsy was performed and showed a paucity of bile ducts. Unexpectedly, admission studies showed a blood glucose of 30. Her hypoglycemia did not recover with 5% dextrose containing intravenous fluids nor frequent feeding. Laboratory studies drawn during an episode of hypoglycemia showed low insulin, cortisol, and growth hormone levels. Total and free carnitine, plasma amino acids, lactate, and beta-hydroxybutyrate were within normal limits. She subsequently had brain imaging, which showed an ectopic neurohypophysis and non-visualized adenohypophysis and pituitary stalk. The final cause of her cholestasis was determined to be panhypopituitarism.

Discussion: The differential diagnosis of cholestasis in a two-month-old is broad and includes anatomical, genetic, metabolic, and infectious etiology (Table 1).

Biliary atresia is a disease that results in the obliteration of bile ducts, and is a common cause of infantile cholestasis. Direct hyperbilirubinemia in infants two months and younger requires prompt workup for biliary atresia due to the urgency of the palliative Kasai procedure. Outcomes of the Kasai procedure are improved if performed prior to 60 days of life. Liver biopsy is the most accurate way to diagnose biliary atresia, with bile duct proliferation seen as the most sensitive and specific feature. Instead of bile duct proliferation, our patient had a paucity of the intralobular hepatic bile ducts, making biliary atresia less likely.

Our patient’s persistent hypoglycemia prompted consideration of alternative etiologies for cholestasis. Obtaining both hormone levels and metabolic studies during an episode of hypoglycemia was critical to diagnosing her panhypopituitarism. Importantly, the patient was noted to have hypoglycemia in the NICU that was attributed to her mother’s GDM, and critical hypoglycemia labs were not drawn at that time.

Conclusion: In a patient two-months-old or younger who presents with conjugated hyperbilirubinemia, it is important to rule out biliary atresia due to the urgency of palliation. However, it is vital to maintain a broad differential for cholestasis that extends beyond liver pathologies, and to obtain critical metabolic and endocrine labs during episodes of hypoglycemia.