Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management
Objective: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2017-09-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | http://www.endocrineconnections.com/content/6/7/540.full |
| _version_ | 1818891230162976768 |
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| author | Benjamin G Challis Andrew S Powlson Ruth T Casey Carla Pearson Brian Y Lam Marcella Ma Deborah Pitfield Giles S H Yeo Edmund Godfrey Heok K Cheow V Krishna Chatterjee Nicholas R Carroll Ashley Shaw John R Buscombe Helen L Simpson |
| author_facet | Benjamin G Challis Andrew S Powlson Ruth T Casey Carla Pearson Brian Y Lam Marcella Ma Deborah Pitfield Giles S H Yeo Edmund Godfrey Heok K Cheow V Krishna Chatterjee Nicholas R Carroll Ashley Shaw John R Buscombe Helen L Simpson |
| author_sort | Benjamin G Challis |
| collection | DOAJ |
| description | Objective: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period.
Design: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed.
Results: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged
I–IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden.
Conclusion: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease. |
| first_indexed | 2024-12-19T17:37:30Z |
| format | Article |
| id | doaj.art-5e4a457eaf8b49049ef3637d4624361e |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-19T17:37:30Z |
| publishDate | 2017-09-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-5e4a457eaf8b49049ef3637d4624361e2022-12-21T20:12:17ZengBioscientificaEndocrine Connections2049-36142049-36142017-09-016748949710.1530/EC-17-0076Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and managementBenjamin G Challis0Andrew S Powlson1Ruth T Casey2Carla Pearson3Brian Y Lam4Marcella Ma5Deborah Pitfield6Giles S H Yeo7Edmund Godfrey8Heok K Cheow9V Krishna Chatterjee10Nicholas R Carroll11Ashley Shaw12John R Buscombe13Helen L Simpson14Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK; Wolfson Diabetes and Endocrine Centre, Addenbrooke’s Hospital, Cambridge, UK; IMED Biotech Unit, Clinical Discovery Unit, AstraZeneca, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK; Wolfson Diabetes and Endocrine Centre, Addenbrooke’s Hospital, Cambridge, UKWolfson Diabetes and Endocrine Centre, Addenbrooke’s Hospital, Cambridge, UKWolfson Diabetes and Endocrine Centre, Addenbrooke’s Hospital, Cambridge, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UKWolfson Diabetes and Endocrine Centre, Addenbrooke’s Hospital, Cambridge, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge, UK; Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge, UKDepartment of Radiology, Addenbrooke’s Hospital, Cambridge, UK; Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge, UKDepartment of Diabetes and Endocrinology, UCLH NHS Foundation Trust, London, UKObjective: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. Design: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. Results: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I–IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. Conclusion: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease.http://www.endocrineconnections.com/content/6/7/540.fullinsulinomahypoglycaemiaPRRTWES |
| spellingShingle | Benjamin G Challis Andrew S Powlson Ruth T Casey Carla Pearson Brian Y Lam Marcella Ma Deborah Pitfield Giles S H Yeo Edmund Godfrey Heok K Cheow V Krishna Chatterjee Nicholas R Carroll Ashley Shaw John R Buscombe Helen L Simpson Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management Endocrine Connections insulinoma hypoglycaemia PRRT WES |
| title | Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management |
| title_full | Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management |
| title_fullStr | Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management |
| title_full_unstemmed | Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management |
| title_short | Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management |
| title_sort | adult onset hyperinsulinaemic hypoglycaemia in clinical practice diagnosis aetiology and management |
| topic | insulinoma hypoglycaemia PRRT WES |
| url | http://www.endocrineconnections.com/content/6/7/540.full |
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