Endocrine Abstracts

Case history: We report 7 weeks old with central diabetes insipidus, holoprosencephaly (HPE), immunodeficiency and severe colitis. She was first admitted with severe diarrhoea and hypernatremia. A diagnosis of central diabetes insipidus (CDI) was made and she was commenced on subcutaneous desmopressin (DDAVP). Her initial hypothalamic–pituitary axis (HPA) was normal (ACTH 10 ng/l, cortisol 635 nmol/l, GH 23 μg/l and TSH 3.30 μ/l). However repeated cortisols and ACTH were low (cortisol 82 nmol/l and ACTH <5 ng/l) demonstrating HPA dysfunction and she was commenced on hydrocortisone therapy (10 mg/m²). A diagnosis of hypopituitarism was considered and thus MRI scan was done which revealed lobar HPE. Florid colitis and central salt wasting made electrolytes and fluid balance management difficult. Total parenteral nutrition was continued for 6 weeks with several failed attempts to re-introduce oral feeds. A gastroscopy and colonoscopy confirmed enterocolitis and she was commenced on sulfasalazine 50 mg QDS and probiotic therapy. Over 12 weeks hospital stay she developed three line and two urinary tract infections. Her immunology screen identified very low IgG (0.1 g/l), IgA (0.07 g/l), raised IgM (1.17 g/l) and normal T cell immunophenotype. She was started on intravenous immunoglobulin infusions. IPEX syndrome was considered in view of the combination of immune deficiency, endocrine problems and colitis; however she had normal FoxP3 expression and CD4+CD25+CD127lo cell counts. She was discharged after 3 month on DDAVP and hydrocortisone. Her colitis has stabilised on sulphasalazine and probiotics but she remains on fortnightly immunoglobulin infusions. She has normal developmental milestones to date.

Conclusion: This case report highlights the complexity of managing fluid and electrolyte balance in CDI especially in the light of unresolving colitis. We believe that this is the first case report of CDI, HPE, immunodeficiency and severe colitis in infancy. Genetic comparative genomic hybridisation micro array studies are awaited to clarify this complex phenotype.