SUN-273 Diazoxide Use to Limit Weight Gain and Reduce Appetite in a Normoglycaemic Child with Previous Congenital Hyperinsulinism

Diazoxide use to suppress insulin production and achieve weight loss is an area of research interest in obese adults with hyperinsulinaemia, with little success to date. Its use for the purpose of weight management has not, to our knowledge, been described in normoglycaemic children with transient congenital hyperinsulinism. In this case we describe successful use of diazoxide to curtail excessive weight gain in a child who was previously diagnosed with congenital hyperinsulinism but is no longer hypoglycaemic. A 7 day old boy was diagnosed with hyperinsulinism based on an insulin level of 46.1mIU/L (2.6-24.9) and paired glucose of 2.2mmol/L. He was macrosomic at birth, weighing 3.86kg at 36 weeks gestation (99(th) centile) but was not dysmorphic. Genetic testing later revealed a variant of uncertain significance in the ABCC8 gene which has previously been described in congenital hyperinsulinism. The same variant was found in his older half-sister who had transient hyperinsulinism requiring diazoxide therapy for two years. This boy’s hypoglycaemia responded to diazoxide at 7.5mg/kg/day in three divided doses. By six months of age he had “grown out” of his diazoxide dose, now 1.4mg/kg/day, which was well below the therapeutic range of 5-15mg/kg/day. Frequent blood glucose checks showed no evidence of hypoglycaemia on the sub-therapeutic dose. At this time excessive weight gain was noted to +4.5 SD above the mean for age despite an appropriate diet during the day. The boy’s mother also described frequent nocturnal arousals seeking feeds (600mL of milk being given overnight) which did not improve with behavioural strategies. The dose of diazoxide was therefore increased back into the therapeutic range with the rationale that the boy may still have hyperinsulinism that was severe enough to drive weight gain and appetite, yet not severe enough to cause detectable hypoglycaemia. The boy’s weight gain slowed on a diazoxide dose of 7.5mg/kg/day and plateaued on 9mg/kg/day (weight +3.6 SD at 14 months old). The overnight wakening for feeds continued until the distribution of the dose was altered to give a larger proportion (just below 50%) of the dose at night. Within two months of this change he his overnight arousals had reduced from six to three times per night. The boy remained normoglycaemic on the increased dose of diazoxide. This case suggests that, even after normoglycaemia is established, weight gain and appetite may still be driven by residual hyperinsulinism in cases of resolving transient congenital hyperinsulinism. Diazoxide may be useful in such cases to curtail excessive weight gain and reduce appetite.