Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism-The UK Perspective

Antonia Dastamani; Daphne Yau; Clare Gilbert; Kate Morgan; Paolo De Coppi; Ross J Craigie; Jamshed Bomanji; Lorenzo Biassoni; Rakesh Sajjan; Sarah E Flanagan; Jayne A L Houghton; Senthil Senniappan; Mohammed Didi; Mark J Dunne; Indraneel Banerjee; Pratik Shah

doi:10.1210/jendso/bvac033

Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism-The UK Perspective

J Endocr Soc. 2022 Mar 15;6(6):bvac033. doi: 10.1210/jendso/bvac033. eCollection 2022 Jun 1.

Authors

Antonia Dastamani¹, Daphne Yau², Clare Gilbert¹, Kate Morgan¹, Paolo De Coppi³, Ross J Craigie⁴, Jamshed Bomanji⁵, Lorenzo Biassoni⁶, Rakesh Sajjan⁷, Sarah E Flanagan⁸, Jayne A L Houghton⁸, Senthil Senniappan⁹, Mohammed Didi⁹, Mark J Dunne¹⁰, Indraneel Banerjee², Pratik Shah^{1

11}

Affiliations

¹ Endocrinology Department, Great Ormond Street Hospital for Children, London, UK.
² Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK.
³ Department of Surgery, Great Ormond Street Hospital for Children, London, UK.
⁴ Department of Paediatric Surgery, Royal Manchester Children's Hospital, Manchester, UK.
⁵ Nuclear Medicine Department, UCL Hospitals NHS Foundation Trust, London, UK.
⁶ Nuclear Medicine Department, Great Ormond Street Hospital for Children, London, UK.
⁷ Nuclear Medicine Department, Royal Manchester Children's Hospital, Manchester, UK.
⁸ Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
⁹ Department of Paediatric Endocrinology, Alder Hey Children's Hospital NHS Trust, Liverpool, UK.
¹⁰ School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
¹¹ Genetics and Genomic Medicine Programme, University College London (UCL) Great Ormond Street Institute of Child Health, London, UK.

Abstract

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery.

Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort.

Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018.

Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose.

Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management.

Keywords: ABCC8 gene; focal lesion; hyperinsulinemic hypoglycemia.