Introduction: Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as Congenital Hyperinsulinism (CHI). Hypoglycaemia is the main feature of CHI, and early diagnosis and immediate management are essential to reduce the high risk of neurological damage. Diazoxide is the mainstay of medical treatment, with surgery being an option in appropriate cases.
Objective: To describe management and outcome of patients with hyperinsulinemic hypoglycaemia within our service.
Methods: Children diagnosed with HH were identified between 2009 and 2017. Clinical course, genetic data, interventions and follow-up data were documented.
Results: A total of 39 children (25 males) were identified, with increasing frequency of referrals during the study period (24/39 during 20152017). Seven patients with secondary and syndromic HH were excluded. 26/32 (81.2%) presented within the first 72 hours of life, 27/32 (84.3%) were born at term. Median birth weight was 3201gm (range 19164610 g). Most were born with an appropriate weight for gestational age (62.5%), only (15.6%) were large for gestational age. Maximum glucose requirement ranged between 6.718.8 mg/kg per min (median 13.1). Median insulin level in critical samples was 11.9 mIU/l (range 1.3110). Diazoxide was started in all patients. Most patients responded, however 7 did not and required octreotide/continuous feeding, with 6/7 requiring surgery. Adverse effects to diazoxide therapy requiring discontinuation were observed in 4 patients, mainly pulmonary hypertension. Genetic mutations were detected in 12/32 (37.5%), (9 K-ATP channel mutations, 3 GLUD 1 mutations). Hyperinsulinism resolved in conservatively treated patients within 12 months in 11/32 (34.3%) compared to 14/32 (43.7%) requiring more than 12 months of medication with 11/14 having no identifiable mutation. A total of 7 (21.8%) patients underwent pancreatectomy (3-subtotal/near-total, 4-focal). Patients with subtotal/near total pancreatectomy still required diazoxide/octreotide post-surgery, with 2/3 developing diabetes.
Conclusion: Although macrosomia and SGA are risk factors, most babies in our cohort were of normal birth weight. Initial glucose requirement and insulin level at diagnosis do not influence disease outcome. Genetic mutation does not exclude medical remission; long-term conservative treatment of CHI is feasible as surgery does not guarantee complete remission but carries risk of pancreatic dysfunction. The need for ongoing treatment in absence of gene mutations suggests that there may be other novel genetic mechanisms involved in regulating insulin secretion. Early management of hypoglycaemia remains critical to prevent long term neurological deficits.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology