ESPE Abstracts (2015) 84 P-3-1078

Long Acting Somatostatin Analogues in the Management of Congenital Hyperinsulinism in Cases with Poor Compliance to Conventional Therapy

Huseyin Demirbileka, Kahraman Oncelb, Mehmet Nuri Ozbekb,c, Ahmet Denizb, Birsen Baysalb, Ved Bhushan Aryad, Sarah E Flanagane, Sian Ellarde & Khalid Hussaind

aDepartments of Paediatric Endocrinology, Faculty of Medicine, Hacettepe University, Ankara, Turkey; bGazi Yasargil Training and Research Hospital, Paediatrics, Diyarbakir, Turkey; cGazi Yasargil Training and Research Hospital, Paediatric Endocrinology, Diyarbakir, Turkey; dDepartments of Paediatric Endocrinology, University College London, Institute of Child Health, Great Ormond Street Hospital for Children, London, UK; eUniversity of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, UK

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.

Table 1 Presenting age, genetics, treatment and follow up of patients (for abstract P3-1078).
Patient 1Patient 2Patient 3Patient 4Patient 5
Age of diagnosis (week)1st week1st week1st week2nd week1st week
Age at oLAR therapy (year)
MutationHomozygous c.3512del (ABCC8)Homozygous c.3512del (ABCC8)Homozygous c.3554C>A (ABCC8)Homozygous c.3554C>A (ABCC8)NA
Octreotide dose (μg/kg per day)10513.32010
Diazoxide dose (mg/kg per day)10107.51515
OctreotideLAR (mg/28 day)3030303030
Baseline TFT’s EuthyroidEuthyroidEuthyroidEuthyroidEuthyroid
TFT’s at follow upEuthyroidEuthyroidEuthyroidEuthyroidEuthyroid
Linear growthNormalNormalNormalNormalNormal
Baseline IGF1/IGFBP3 (μg/l)108/3000241/403053/3140 NA/4280101/3020
IGF1/IGFBP3 follow-up (μg/l)NA/NANA/NA136/NANA/NA167/4180
Gallbladder pathologyNoNoNoNoNo
Side effect (other)NoNoNoNoNo

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.