Amalie G Rasmussen1,2, Maria Melikian3, Evgenia Globa4, Sönke Detlefsen2,5,6, Lars Rasmussen5,7, Henrik Petersen8, Klaus Brusgaard9, Annett H Rasmussen1, Michael B Mortensen5,7, Henrik T Christesen1,2,5. 1. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. 2. Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. 3. Department of Pediatric Endocrinology, Endrocrine Research Center, Moscow, Russia. 4. Department of Pediatric Endocrinology, Ukrainian Research Center of Endocrine Surgery, Kyiv, Ukraine. 5. OPAC, Odense Pancreas Center, Odense University Hospital, Odense, Denmark. 6. Department of Pathology, Odense University Hospital, Odense, Denmark. 7. Department of Surgery, Odense University Hospital, Odense, Denmark. 8. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. 9. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Abstract
BACKGROUND/ OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with transient or persistent hypoglycemia. Histologically, focal, diffuse, and atypical forms of CHI exist, and at least 11 disease-causing genes have been identified. METHODS: We retrospectively evaluated the treatment and outcome of a cohort of 40 patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark, from January 2000 to May 2017. RESULTS: Twenty-two patients (55%) could not be managed with medical monotherapy (diazoxide or octreotide) and six (15%) patients developed severe potential side effects to medication. Surgery was performed in 17 (43%) patients with resection of 66% to 98% of the pancreas. Surgically treated patients had more frequently KATP -channel gene mutations (surgical treatment 12/17 vs conservative treatment 6/23, P = .013), highly severe disease (15/17 vs 13/23, P = .025) and clinical onset <30 days of age (15/17 vs 10/23, P = .004). At last follow-up at median 5.3 (range: 0.3-31.3) years of age, 31/40 (78%) patients still received medical treatment, including 12/17 (71%) after surgery. One patient developed diabetes after a 98% pancreatic resection. Problematic treatment status was seen in 7/40 (18%). Only 8 (20%) had clinical remission (three spontaneous, five after pancreatic surgery). Neurodevelopmental impairment (n = 12, 30%) was marginally associated with disease severity (P = .059). CONCLUSIONS: Persistent, non-focal CHI remains difficult to manage. Neurological impairment in 30% suggests a frequent failure of prompt and adequate treatment. A high rate of problematic treatment status at follow-up demonstrates an urgent need for new medical treatment modalities.
BACKGROUND/ OBJECTIVE:Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with transient or persistent hypoglycemia. Histologically, focal, diffuse, and atypical forms of CHI exist, and at least 11 disease-causing genes have been identified. METHODS: We retrospectively evaluated the treatment and outcome of a cohort of 40 patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark, from January 2000 to May 2017. RESULTS: Twenty-two patients (55%) could not be managed with medical monotherapy (diazoxide or octreotide) and six (15%) patients developed severe potential side effects to medication. Surgery was performed in 17 (43%) patients with resection of 66% to 98% of the pancreas. Surgically treated patients had more frequently KATP -channel gene mutations (surgical treatment 12/17 vs conservative treatment 6/23, P = .013), highly severe disease (15/17 vs 13/23, P = .025) and clinical onset <30 days of age (15/17 vs 10/23, P = .004). At last follow-up at median 5.3 (range: 0.3-31.3) years of age, 31/40 (78%) patients still received medical treatment, including 12/17 (71%) after surgery. One patient developed diabetes after a 98% pancreatic resection. Problematic treatment status was seen in 7/40 (18%). Only 8 (20%) had clinical remission (three spontaneous, five after pancreatic surgery). Neurodevelopmental impairment (n = 12, 30%) was marginally associated with disease severity (P = .059). CONCLUSIONS: Persistent, non-focal CHI remains difficult to manage. Neurological impairment in 30% suggests a frequent failure of prompt and adequate treatment. A high rate of problematic treatment status at follow-up demonstrates an urgent need for new medical treatment modalities.
Authors: Indraneel Banerjee; Julie Raskin; Jean-Baptiste Arnoux; Diva D De Leon; Stuart A Weinzimer; Mette Hammer; David M Kendall; Paul S Thornton Journal: Orphanet J Rare Dis Date: 2022-02-19 Impact factor: 4.123
Authors: A P Bjarnesen; P Dahlin; E Globa; H Petersen; K Brusgaard; L Rasmussen; M Melikian; S Detlefsen; H T Christesen; M B Mortensen Journal: BJS Open Date: 2021-03-05