Pharmacokinetics of Long Acting Somatostatin Analogue (Lanreotide) Therapy in Hyperinsulinaemic Hypoglycaemia (HH) and Understanding Its Molecular Action Via Somatostatin Receptors By Immunohistochemistry

Presentation Number: SAT 611
Date of Presentation: April 1st, 2017

Pratik Shah*1, Sofia A Rahman2, Sharon McElroy3, Clare Gilbert3, Kate Morgan3, Louise Hinchey3, Maria Guemes1, Senthil Senniappan4, Roberta Button3, Rebecca Margetts3, Hannah Levy3, Carles Marti5, Carles Celma Lezcano5, Rakesh Amin1 and Khalid Hussain6
1Great Ormond Street Hospital for Children and UCL Institute of Child Health, London, United Kingdom, 2UCL Great Ormond Street Institute of Child Health, London, 3Great Ormond Street Hospital for Children, London, United Kingdom, 4Alder Hey Childrens Hospital, Liverpool, 5Kymos Pharma Services, Barcelona, 6UCL Great Ormond Street Institute of Child Health, London, United Kingdom

Abstract

Background: Hyperinsulinaemic hypoglycaemia is one of the common causes of hypoglycaemia in children. Diazoxide and octreotide are first and second-line of treatment for HH respectively. Children not responding to medical therapy undergo pancreatectomy and as a result there is need to develop newer therapy to manage this complex condition. Long-acting somatostatin analogue (Lanreotide or LA) has been used in adults with neuroendocrine conditions through its effect on somatostatin receptors 2 (SSTR2) and 5 (SSTR5).

Objective and hypotheses: 1) To evaluate the efficacy, safety and pharmacokinetics of LA therapy in children with HH. 2) To determine somatostatin receptor expression on pancreatic alpha, beta and delta cells of HH patients on LA therapy.

Method: Children were started on 30mg LA administered every 4-weekly. Plasma LA concentrations were collected in both groups (those on diazoxide and octreotide) and measured by radioimmunoassay (>3years of age). The samples were collected at times 0,+1,+2,+4,+24 and +96 hours post 1st dose, before each dose for 6 months and then at 12 months of treatment. Children >3 years of age had paediatric quality of life (PedsQL) assessment and continuous glucose monitoring (CGMS) pre and 1-year post-LA. Formalin fixed pancreatic tissue sections were studied on those children who had pancreatectomy prior to starting LA therapy for immunohistochemistry.

Results: 31 children were commenced on LA. Pharmacokinetic data on 21 children showed that LA concentrations significantly peak after 2-4 hours of administration. After the first dose of LA, there was a strong correlation (r=0.836, p-value<0.001) between the LA concentration and blood glucose. However before each dose of lanreotide, there is weak correlation (r=0.382, p-value<0.001) between the lanreotide concentration and blood glucose. There was no significant difference in LA concentrations between two groups (diazoxide and octreotide) at each time period. Blood glucose concentrations <3.5mmol/l were significantly reduced 1-year post-LA compared with pre-LA (p-value = 0.004). The quality of life improved in health, emotion, social, school and psychosocial functioning 1 year post commencing LA. SSTR2 and SSTR5 expression was greater in diffuse and normal compared to focal pancreatic tissue.

Conclusion: This is the first study in children to undertsand the pharmacokinetics of LA therapy in hyperinsulinaemic hypoglycaemia. We observed significant benefits in terms of frequency of hypoglycaemia and quality of life one year after starting LA therapy. Immunohistochemistry suggest that diffuse disease is more likely to respond to LA than focal disease.

 

Nothing to Disclose: PS, SAR, SM, CG, KM, LH, MG, SS, RB, RM, HL, CM, CCL, RA, KH