Background: Cholestatic hepatopathy is a rare but serious threat to neonates and young infants. Their immature hepatic excretory function predisposes for severe and rapidly progressive hepatic injury. Because of the wide range of possible etiologies, it is often difficult to make an accurate diagnosis. One rare endocrine cause can be primary or secondary hypocortisolism.
Case presentation: i) A 7-week-old term-born female with cholestasis, elevated liver enzymes, fatigue and history of hypoglycaemic seizures was referred to our centre. Parents are consanguineous. Conjugated bilirubin was 9.6 mg/dl (<0.3), AST 884 U/l (<79), ALT 215 U/l (<48). ACTH was elevated (>2000 pg/ml) and serum cortisol was not detectable. Mutational analysis revealed a homozygous mutation in melanocortin 2 receptor-associated protein (MRAP) as cause of ACTH resistance due to defective receptor signalling. ii) A 2-day-old full-term girl presented due to hypoglycaemic seizures. She was treated with intravenous glucose. At this time only Gamma-GT was elevated to 300 U/l (<181). She was discharged 13 days later with normalized blood sugars. Two weeks later she developed cholestasis, anaemia and elevated liver enzymes: conjugated bilirubin was 5.35 mg/dl (<0.3), AST 797 U/l (<79), ALT 278 (<48). Basal cortisol levels were decreased (0.3 μg/dl) and ACTH and cortisol showed a diminished reaction on stimulation with CRH (ACTH max. 16.9 pg/ml and cortisol max 4.9 μg/dl). MRI revealed septo-optic pituitary dysplasia. In both cases hydrocortisone replacement led to complete normalization of liver enzymes and bilirubin.
Conclusion: Since symptoms may be unspecific or very subtle, diagnosis of neonatal/infantile hypocorticsolism can easily be missed with significant delay in starting hormonal replacement therapy. Therefore, we strongly emphasize to analyse cortisol levels in the work-up of cholestasis in newborns and infants in particular in association with severe hypoglycaemia.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology