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      Factitious Hypoglycemia Caused by a Unique Pattern of Drug Use: A Case Report

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          Abstract

          Introduction

          Factitious hypoglycemia, caused by the surreptitious use of insulin and sulfonylureas, is one of the most challenging differential diagnoses of hypoglycemia. Diagnosis is usually established via exclusion with respect to the special patterns of plasma insulin and C-peptide during hypoglycemic episodes.

          Case Presentation

          We report a case of recurrent hypoglycemic episodes and confusing patterns of insulin and C-peptide levels. In the primary evaluations, insulinoma was suspected considering the high plasma concentrations of insulin and C-peptide, besides negative urine and plasma sulfonylureas during hypoglycemic episodes. Considering the normal imaging studies and refractory hypoglycemia to medical therapy, distal pancreatectomy was performed. The patient had no episodes of hypoglycemia after the surgery. Five months later, similar episodes recurred. Further investigations revealed different plasma concentrations of insulin and C-peptide in each hypoglycemic episode. Regarding various biochemical patterns during hypoglycemia and absence of evidence supporting other differential diagnoses, we suspected factitious causes. Close observation revealed that the patient had a history of intermittent glyburide consumption and analog insulin injection.

          Discussion

          Most commercial insulin immunoassays can only detect human insulin and lack the ability to identify synthetic analog insulin. In addition, common detection methods for sulfonylureas and meglitinides are of low diagnostic value in the human plasma and urine. These laboratory defects can lead to the misdiagnosis of insulinoma or noninsulin-mediated hypoglycemia due to the surreptitious use of insulin secretagogues or analog insulin, respectively. Therefore, due to the lack of any definitive laboratory findings, clinical suspicion is the best strategy for diagnosis.

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          Most cited references11

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          LC-MS/MS in the Clinical Laboratory - Where to From Here?

          Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in clinical laboratories during the last 10-15 years. It offers analytical specificity superior to that of immunoassays or conventional high performance/pressure liquid chromatography (HPLC) for low molecular weight analytes and has higher throughput than gas chromatography-mass spectrometry (GC-MS). Drug/Toxicology and Biochemical Genetics/Newborn Screening laboratories were at the vanguard of clinical LC-MS/MS use, but have been eclipsed by Endocrine laboratories. In USA reference/referral laboratories, most steroids and biogenic amines are now assayed by LC-MS/MS, and the technology has started to penetrate into smaller laboratories. Assays for mineralo- and gluco-corticoids and their precursors, sex steroids, metanephrines and 25-hydroxy vitamin D highlight the advantages of LC-MS/MS.However, several limitations of LC-MS/MS have become apparent, centring on the interacting triangle of sensitivity - specificity - throughput. While sample throughput is higher than for conventional HPLC or GC-MS, it lags behind automated immunoassays. Techniques which improve throughput include direct sample injection, LC-multiplexing and samplemultiplexing. Measures to improve specificity and sensitivity include sample clean-up and optimising chromatography to avoid interferences and ion suppression due to sample-matrix components. Next generation instrumentation may offer additional benefits.The next challenge for clinical LC-MS/MS is peptide/protein analysis. The quest for multi-biomarker profiles for various diseases has largely failed, but targeted peptide and protein testing by LC-MS/MS, directed at analytical and clinical questions that need to be answered, is proving highly successful. We anticipate that this will result in similar growth of clinical protein/peptide LC-MS/MS as has been seen for low molecular weight applications.
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            Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues.

            Blood insulin and C-peptide are key investigations in the differential diagnosis of hypoglycaemia. Analogues of insulin have modified primary-sequences compared to native human insulin, as such may not cross react with insulin assays. This has important implications in detecting surreptitious or malicious insulin administration. The aim of this study is to assess the cross-reactivity of all insulins currently listed in the British National Formulary (BNF65, 2013) in clinical insulin assays currently used in UK clinical laboratories.
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              Factitious hyperinsulinism leading to pancreatectomy: severe forms of Munchausen syndrome by proxy.

              Clinical history and inappropriate insulin secretion during hypoglycemic episodes permit the diagnosis of hyperinsulinism. We report 2 cases of factitious hyperinsulinism leading to partial pancreatectomy. Case 1 was an 8-year-old girl who presented with severe hypoglycemia and elevated insulin and C-peptide levels. Catheterization of pancreatic veins was performed to localize the excess insulin secretion. Insulinoma was suspected, and partial pancreatectomy was performed. Ten days after surgery, severe hypoglycemia recurred with severely elevated plasma insulin levels (x100) but very low C-peptide plasma levels, suggesting factitious hyperinsulinemia. Hypoglycemic episodes before surgery were provoked by oral sulfonamides; postoperative episodes were caused by parenteral insulin. Falsified prescriptions for sulfonamides and insulin by the mother, a nurse, were found. Case 2 was a 6-month-old girl who presented with seizures and hypoglycemia but had a symptom-free interval of many months afterward. At 2 years of age, repeated hypoglycemic seizures and elevated insulin plasma levels suggested congenital hyperinsulinism. C-peptide plasma level, measured once, was normal, but blood sampling was performed 15 minutes after a hypoglycemic episode. Partial pancreatectomy was performed. Two weeks after surgery, hypoglycemic seizures recurred, and the patient was admitted for pancreatic vein catheterization. This investigation was performed during hypoglycemia and revealed high insulin levels and undetectable C-peptide levels, suggesting factitious hypoglycemia. Insulin/C-peptide ratio analysis is crucial to assess factitious hypoglycemia, although sulfonamide-induced hypoglycemia is not thereby detected. One percent (2 of 250) of all cases of hyperinsulinemic hypoglycemia in our unit have been identified as Munchausen syndrome by proxy. Atypical disease history should raise the question of factitious hypoglycemia.
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                Author and article information

                Contributors
                Journal
                Int J Endocrinol Metab
                Int J Endocrinol Metab
                10.5812/ijem.
                Kowsar
                International Journal of Endocrinology and Metabolism
                Kowsar
                1726-913X
                1726-9148
                20 December 2017
                January 2018
                : 16
                : 1
                : e62591
                Affiliations
                [1 ]Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
                [2 ]Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Corresponding author: Sayed Mahmoud Sajjadi-Jazi, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Tel: +98-9133258106, E-mail: mahmood.sajadi@ 123456gmail.com
                Article
                10.5812/ijem.62591
                5961186
                94d8f083-95dc-4c46-9810-871e32b43f23
                Copyright © 2018, International Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 14 April 2017
                : 08 October 2017
                : 13 November 2017
                Categories
                Case Report

                factitious,hypoglycemia,insulin,glyburide
                factitious, hypoglycemia, insulin, glyburide

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