LAUSR

Pituitary Stalk Interruption Syndrome (PSIS) is a rare congenital disorder causing multiple pituitary hormone deficiencies. Though neonatal cholestasis has various causes, PSIS is an uncommon and often overlooked etiology, likely linked to cortisol deficiency. We report two cases of neonatal cholestasis due to severe cortisol deficiency, highlighting the need to consider PSIS in differential diagnosis. We report two cases of a two-month-old female infant and a three-day-old male newborn presenting with neonatal cholestasis. Initial workups ruled out common infectious and metabolic causes. The association of hypoglycemia led to considering endocrine causes and tests revealed severe cortisol deficiency, with one case also exhibiting hypothyroidism. Brain MRI confirmed PSIS in both patients. Hormone replacement therapy with hydrocortisone, and levothyroxine when needed, led to resolution of cholestasis and stabilization of glucose levels. Follow-up showed persistent growth issues, prompting growth hormone (GH) therapy initiation in one case, while GH testing was planned in the other. Neonatal cholestasis can be an early and often transient manifestation of PSIS, associated with cortisol deficiency. Early recognition and prompt hormone replacement therapy are essential for improving clinical outcomes. A comprehensive hormonal evaluation, including cortisol, thyroid, and GH levels, alongside pituitary MRI, is crucial for timely diagnosis and management.