Background: Congenital hyperinsulinism (CHI), is the most common cause of severe hypoglycaemia in neonates and infants. The cornerstone of medical therapy is diazoxide. Octreotide, a somatostatin analogue, is the second therapeutic option in diazoxide unresponsive cases. However, due to its short half-life and requirement of multiple daily doses, lack of compliance may cause recurring hypoglycaemia and related neurological deficits, particularly for the family with low socioeconomic status. Long acting somatostatin analogues that provide good glycaemic control by a monthly injection, might help in the management of CHI patients who have poor compliance with conventional medical therapy. Herein, we report the management of 5 patients with diazoxide unresponsive CHI who have poor compliance, using the long-acting somatostatin analogue, octreotideLAR (oLAR).
Patients: Patient details are summarised in Table 1. Patients 1, 2 (siblings) and 3 were diagnosed in the neonatal period and were diazoxide unresponsive but, octreotide responsive. All developed severe neurodevelopmental deficits and epilepsy due to recurring hypoglycaemic episodes as a result of the poor compliance. Patient 4 was the first cousin of patient 3 and had another sister with CHI due to identical mutation and severe mental-motor retardation. This patients was commenced oLAR at a younger age and had favorable blood measurements and neurological development. Patient 5 was also started on oLAR therapy at a younger age and had a good glycaemic control, consequently normal neurological development. In all five patients diazoxide and multidose octreotide was weanned off successfully. Furthermore, we have not observed any severe acute or long-term side effects requiring treatment withdrawal.
|Patient 1||Patient 2||Patient 3||Patient 4||Patient 5|
|Age of diagnosis (week)||1st week||1st week||1st week||2nd week||1st week|
|Age at oLAR therapy (year)||5.8||9.8||4.0||1.3||1.9|
|Mutation||Homozygous c.3512del (ABCC8)||Homozygous c.3512del (ABCC8)||Homozygous c.3554C>A (ABCC8)||Homozygous c.3554C>A (ABCC8)||NA|
|Octreotide dose (μg/kg per day)||10||5||13.3||20||10|
|Diazoxide dose (mg/kg per day)||10||10||7.5||15||15|
|OctreotideLAR (mg/28 day)||30||30||30||30||30|
|TFTs at follow up||Euthyroid||Euthyroid||Euthyroid||Euthyroid||Euthyroid|
|Baseline IGF1/IGFBP3 (μg/l)||108/3000||241/4030||53/3140||NA/4280||101/3020|
|IGF1/IGFBP3 follow-up (μg/l)||NA/NA||NA/NA||136/NA||NA/NA||167/4180|
|Side effect (other)||No||No||No||No||No|
Conclusion: Administration of long acting somatostatin analogs (every 28 days) resulted in better compliance and thereby prevented recurring hypoglycaemic episodes and related neurological deficits. In low scoieconomic class with anticipated poor compliance, long acting somatostatin analogs may potentially be the first option in the medical therapy of CHI.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology