ESPE Abstracts

Background: Rapid-onset obesity with hypothalamic dysregulation, hypoventilation and autonomic dysregulation (ROHHAD) is a rare syndrome with a high risk of morbidity and mortality. Blood glucose dysregulation is not widely recognised as a feature of ROHHAD and the mechanism is not well understood. We describe glucose dysregulation in two children with ROHHAD syndrome.

Case 1: The patient presented at 6 years with rapid weight gain (BMI-SDS +2.45). She had hyperprolactinaemia, central diabetes insipidus (DI), growth hormone deficiency (GHD) and central hypothyroidism. MRI pituitary was normal. At 14 years she developed central hypoventilation requiring nocturnal BiPAP. Aged 14 years she developed glucose dysregulation with intermittent hypergylcaemia, HbA1C of 59mmol/mol (NR<48mmol/mol) but a normal oral glucose tolerance test (OGTT). A year later, her HbA1c had risen to 64mmol/mol and she had raised blood sugar level (BSL) on OGTT (2 hours BSL 22.5mmol/L; NR <11.1). She was diagnosed with diabetes and commenced metformin (1g twice daily) and insulin (0.5units/kg/day). Auto-antibodies were negative. BSLs rapidly normalised and insulin was discontinued after one week. Metformin was continued and liraglutide (0.6mg/day for 2 weeks, then 1.2mg/day) was commenced for weight management. Within two months her HbA1c normalised (39mmol/mol). Continuous glucose monitoring sensor (CGMS) showed daily hypoglycaemic episodes with approximately 30% of time <3.9mmol/L. Therefore, liraglutide was discontinued and the hypoglycaemia resolved. BMI-SDS is now +2.72. She continues metformin with normal HbA1c (41mmol/mol), average BSL 7.2mmol/l and 92% time in range.

Case 2: The patient presented in cardio-respiratory arrest aged 4 years following a 6-month period of rapid weight gain (BMI-SDS +3.1). She had central hypoventilation requiring nocturnal BiPAP, central DI, hyperprolactinaemia and GHD. MRI pituitary was normal. Aged 5 years, despite a significant improvement in her BMI-SDS (to +1.35) she had persistent high random BSLs (12-16mmol/L) on multiple occasions. Her OGTT (2 hours BSL 12.2mmol/L) was suggestive of diabetes, but with a normal HbA1c (33mmol/mol) and no symptoms of diabetes. Auto-antibodies were negative. BSLs subsequently normalised and therefore treatment was not commenced.

Conclusions: The mechanism of glucose dysregulation and diabetes in these patients is unclear, possibly related to the hypothalamic or autonomic dysfunction characteristic of ROHHAD. CGMS may be useful in ROHHAD to evaluate glucose dysregulation. Hypoglycaemia is not a well described side-effect of liraglutide, however, in the context of ROHHAD, this could be centrally mediated or due to an exaggerated incretin response. Further exploration is required in this area to understand the underlying, potentially novel, mechanism.