Non-Syndromic Bile Duct Paucity Associated with Subsequent Development of Growth Hormone Deficiency – Report of 3 Patients

Abstract

Purpose: Congenital hypopituitarism is a recognized cause of neonatal hepatitis and rarely presents with bile duct paucity. We report three patients who presented with neonatal cholestasis by 8 to 10 weeks of age. Evaluation for infectious, anatomic and metabolic diseases was normal. They all had normal thyroid function tests and serum glucose levels at the time of presentation. They underwent liver biopsy which showed paucity of bile ducts. All patients had poor growth. One patient had abnormal brain imaging in-utero. Post-natal MRI of the brain showed an absent septum pellucidum. He had a normal eye exam and normal pituitary axis, by biochemical studies, as an infant. The second patient had an MRI of the brain as part of a work-up for seizures. This imaging revealed agenesis of the corpus callosum and colpocephaly. The third patient had an MRI of the brain at three and a half years of age for evaluation of failure to thrive (FTT) which demonstrated an element of corpus callosum dysgenesis and an ectopic posterior pituitary gland. All patients had supportive therapy for cholestasis and their liver function tests were normalized between 5–8 months of age. All patients were followed for failure to thrive and referred to endocrinology for comprehensive growth evaluation. All three patients had an inadequate growth hormone (GH) response to clonidine stimulation testing and low levels of somatomedin at 14 months, 16 months and 4 years of age, respectively. They started on GH replacement and their linear growth caught up within 2 years. Two of the three have subsequently required additional pituitary hormone replacement (i.e., first patient thyroxine and third patient thyroxine and cortisol). Conclusions: In conclusion, growth hormone deficiency/hypopituitarism should be in the differential diagnosis of cholestasis due to non-syndromic paucity of bile ducts. Failure to thrive is not necessarily due to cholestasis related malabsorption. Patients should be followed longitudinally for GH deficiency even after normal initial evaluations. MRI of the brain can be a helpful diagnostic tool and should be considered in patients with non-syndromic paucity of bile ducts.