Introduction: Septo-optic dysplasia (SOD) is a rare syndrome complex characterized by midline forebrain defects, optic nerve hypoplasia, and hypopituitarism. SOD is usually associated with short stature secondary to growth hormone deficiency. We present an unusual case of SOD with liver cirrhosis and severe insulin resistance at presentation leading to early diabetes and preserved growth.
Case: A seven and half year old boy presented with hypotension, hypercapnoeic respiratory failure and bilateral pneumonia, on background of bilateral blindness due to optic nerve dysplasia (which was known since 6 months of age). His height was 137cm (> 97th centile), weight was 59 kg (> 97th centile). Investigations revealed panhypopituitarism with diabetes insipidus and MRI changes were consistent with septooptic dysplasia. He had raised liver enzymes, hepatosplenomegaly with coarse liver echotexture and portal hypertension. Metabolic liver disease screen was normal. Liver biopsy confirmed micronodular cirrhosis with severe steatosis and negative iron, PAS staining. Soon after, he was diagnosed with type 2 diabetes mellitus and severe insulin resistance. Progressive weight gain has complicated the management. However he achieved an adult height of 180 cm despite growth hormone (GH) deficiency. He did not receive GH therapy. He has been managed at our clinic for panhypopituitarism replacement therapy and type 2 diabetes for the last 12 years.
Discussion Points:
Congenital hypopituitarism is associated with neonatal cholestasis, but liver cirrhosis in childhood is rare. The link between hypopituitarism and hepatic dysfunction will be discussed.
Hypothalamic involvement can directly influence insulin resistance independent of weight gain. Possible relationship of hypothalamic pathology with insulin resistance and early onset diabetes will be explored.
Hyperinsulinemia can also promote growth despite growth hormone deficiency which explains the normal height achieved.
Key references:
1) Polizzi A, et al. Septo-optic dysplasia complex: a heterogeneous malformation syndrome. Pediatric neurology 2006;34:66-71.
2) Loria P, et al.. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol 2009;6:236-47.
3) Nakajima K, et al. Pediatric non-alcoholic steatohepatitis associated with hypopituitarism. J Gastroenterol 2005;40:312-315.
4) Hideyuki Iwayama, et al. Hyperinsulinemia may promote growth without GH in children after resection of suprasellar brain tumors. Endocrine 2011:40:130-133.
5) Trivin C, et al. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index. BMC Paediatrics 2009, 9:24.