A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism
BackgroundThe diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12–18 pmol/L (2–3 mU/L).ObjectiveTo evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.Method...
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doaj-54a946bccc804a0aa5bdef92ae67117d2021-02-19T06:46:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-02-011110.3389/fendo.2020.614993614993A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital HyperinsulinismJulie Siersbæk0Julie Siersbæk1Annette Rønholt Larsen2Annette Rønholt Larsen3Mads Nybo4Henrik Thybo Christesen5Henrik Thybo Christesen6Henrik Thybo Christesen7Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkDepartment of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkHans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkDepartment of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, DenmarkHans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkDepartment of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkOdense Pancreas Center (OPAC), Odense University Hospital, Odense, DenmarkBackgroundThe diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12–18 pmol/L (2–3 mU/L).ObjectiveTo evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.MethodsDiagnostic fasting tests, performed without medication or i.v.-glucose, were investigated in children with a clinical diagnosis of CHI, or idiopathic ketotic hypoglycemia (IKH). The CHI diagnosis was either clinical or by the alternative, p-insulin-free criteria; hypoglycemia plus disease-causing genetic mutations and/or CHI-compatible pancreatic histopathology. We included diagnostic p-insulin samples with simultaneous p-glucose <3.2 mmol/L and used a sensitive insulin assay (Cobas e411 immunoassay analyzer; lower detection limit 1.2 pmol/L; normal range 15.1–147.1 pmol/L). Receiver operating characteristics area under the curve (ROC AUC) values and optimal cut-offs were analyzed for the performance of p-insulin to diagnose CHI.ResultsIn 61 CHI patients, the median (range) p-insulin was 76.5 (17–644) pmol/L compared to 1.5 (1.5–7.7) pmol/L in IKH patients (n=15). The ROC AUC was 1.0 for the diagnosis of CHI defined both by the clinical diagnosis (n=61) and by alternative criteria (n=57). The optimal p-insulin cut-offs were 12.3 pmol/L, and 10.6 pmol/L, at p-glucose <3.2 mmol/L (n=61), and <3.0 mmol/L (n=49), respectively.ConclusionsThe sensitive insulin assay performed excellent in diagnosing CHI with optimal p-insulin cut-offs at 12.3 pmol/L (2.0 mU/L), and 10.6 pmol/L (1.8 mU/L), at p-glucose <3.2 mmol/L, and <3.0 mmol/L, respectively. A sensitive insulin assay may serve to simplify the diagnosis of CHI.https://www.frontiersin.org/articles/10.3389/fendo.2020.614993/fullhypoglycemiacongenital hyperinsulinismchildrendiagnostic performanceimmunoassays |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julie Siersbæk Julie Siersbæk Annette Rønholt Larsen Annette Rønholt Larsen Mads Nybo Henrik Thybo Christesen Henrik Thybo Christesen Henrik Thybo Christesen |
spellingShingle |
Julie Siersbæk Julie Siersbæk Annette Rønholt Larsen Annette Rønholt Larsen Mads Nybo Henrik Thybo Christesen Henrik Thybo Christesen Henrik Thybo Christesen A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism Frontiers in Endocrinology hypoglycemia congenital hyperinsulinism children diagnostic performance immunoassays |
author_facet |
Julie Siersbæk Julie Siersbæk Annette Rønholt Larsen Annette Rønholt Larsen Mads Nybo Henrik Thybo Christesen Henrik Thybo Christesen Henrik Thybo Christesen |
author_sort |
Julie Siersbæk |
title |
A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism |
title_short |
A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism |
title_full |
A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism |
title_fullStr |
A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism |
title_full_unstemmed |
A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism |
title_sort |
sensitive plasma insulin immunoassay to establish the diagnosis of congenital hyperinsulinism |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2021-02-01 |
description |
BackgroundThe diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12–18 pmol/L (2–3 mU/L).ObjectiveTo evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.MethodsDiagnostic fasting tests, performed without medication or i.v.-glucose, were investigated in children with a clinical diagnosis of CHI, or idiopathic ketotic hypoglycemia (IKH). The CHI diagnosis was either clinical or by the alternative, p-insulin-free criteria; hypoglycemia plus disease-causing genetic mutations and/or CHI-compatible pancreatic histopathology. We included diagnostic p-insulin samples with simultaneous p-glucose <3.2 mmol/L and used a sensitive insulin assay (Cobas e411 immunoassay analyzer; lower detection limit 1.2 pmol/L; normal range 15.1–147.1 pmol/L). Receiver operating characteristics area under the curve (ROC AUC) values and optimal cut-offs were analyzed for the performance of p-insulin to diagnose CHI.ResultsIn 61 CHI patients, the median (range) p-insulin was 76.5 (17–644) pmol/L compared to 1.5 (1.5–7.7) pmol/L in IKH patients (n=15). The ROC AUC was 1.0 for the diagnosis of CHI defined both by the clinical diagnosis (n=61) and by alternative criteria (n=57). The optimal p-insulin cut-offs were 12.3 pmol/L, and 10.6 pmol/L, at p-glucose <3.2 mmol/L (n=61), and <3.0 mmol/L (n=49), respectively.ConclusionsThe sensitive insulin assay performed excellent in diagnosing CHI with optimal p-insulin cut-offs at 12.3 pmol/L (2.0 mU/L), and 10.6 pmol/L (1.8 mU/L), at p-glucose <3.2 mmol/L, and <3.0 mmol/L, respectively. A sensitive insulin assay may serve to simplify the diagnosis of CHI. |
topic |
hypoglycemia congenital hyperinsulinism children diagnostic performance immunoassays |
url |
https://www.frontiersin.org/articles/10.3389/fendo.2020.614993/full |
work_keys_str_mv |
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