ESPE Abstracts (2016) 86 FC10.3

Pharmacokinetics of Long Acting Somatostatin Analogue (Lanreotide) Therapy in Hyperinsulinaemic Hypoglycaemia (HH) and Understanding its Molecular Action via Somatostatin Receptors by Immunohistochemistry

Pratik Shaha,b, Sofia Rahmana, Sharon McElroyb, Clare Gilbertb, Kate Morganb, Louise Hincheyb, Maria Guemesa,b, Syeda Alamb, Senthil Senniappanc, Roberta Buttonb, Rebecca Margettsb, Hannah Levyb, Emma Bascompta Santacreud, Carles Morte Martid, Carles Celma Lezcanod, Rakesh Amina,b & Khalid Hussaina,b


aUCL Institute of Child Health, London, UK; bGreat Ormond Street Hospital for Children, London, UK; cAlder Hey Children’s Hospital, Liverpool, UK; dKymos Pharma Services, Barcelona, Spain


Background: Diazoxide and octreotide are first and second-line of treatment for HH respectively. Long-acting somatostatin analogue (Lanreotide, LA) has been used in adults with neuroendocrine conditions through its effect on somatostatin receptors 2 (SSTR2) and 5 (SSTR5).

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

Method: Children were started on 30 mg LA administered every 4-weekly. Plasma LA concentrations were collected in both groups (those on diazoxide and octreotide) and measured by radioimmunoassay (>3 years 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<0.001) between the LA 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 <3.5 mmol/l were significantly reduced 1-year post-LA compared with pre-LA (P=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: 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.

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