Interpreting insulin immunoassays during investigation of apparent spontaneous hypoglycaemia and insulin overdose

Chemmanam, Julie; Isaacs, Michelle; Jones, Graham; Greenfield, Jerry R.; Burt, Morton G.

doi:10.1111/imj.13644

Cited by 9 publications

(5 citation statements)

References 12 publications

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“…In 2001 Sapin et al [ 13 ] first suggested the absence of cross-reactivity with insulin analogues in some assays [ 13 ], which was subsequently confirmed by other groups [ 12 , 14 – 16 ]. There are also a number of publications with clinical cases on this topic [ 17 – 20 ]. Chemmanam et al [ 20 ] reported two cases of hypoglycemia where the diagnosis was initially unclear due to the use of the RE assay.…”

Section: Discussionmentioning

confidence: 99%

“…In both cases insulin concentration was normal when measured with the Roche’s immunoassay, but was appropriately elevated when remeasured with the Advia Centaur immunoassay and a diagnosis of hypoglycemia secondary to insulin analogue administration was made. In addition, this work compared 4 analytical platforms with respect to the detection of 5 insulin preparations [ 20 ]. These cases emphasize that understanding the binding characteristics of the insulin immunoassay used by the laboratory is essential to making a correct diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…There are also a number of publications with clinical cases on this topic [17][18][19][20]. Chemmanam et al [20] reported two cases of hypoglycemia where the diagnosis was initially unclear due to the use of the RE assay. In both cases insulin concentration was normal when measured with the Roche's immunoassay, but was appropriately elevated when remeasured with the Advia Centaur immunoassay and a diagnosis of hypoglycemia secondary to insulin analogue administration was made.…”

Section: Discussionmentioning

confidence: 99%

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Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism

Yukina

Katsobashvili

Platonova

et al. 2022

Clin Diabetes Endocrinol

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Background Hypoglycemic syndrome is a potentially life-threatening condition that can lead to the disruption of brain and internal organ functions, and in severe cases to irreparable consequences or death. Factitious hypoglycemia (FH) is the deliberate use of insulin preparations or oral hypoglycemic drugs with the aim of lowering blood glucose levels into the pathologically-hypoglycemic range. Deliberate administration of insulin analogs may be difficult to prove because they might not have epitopes or containing low affinity epitopes that are the targets of antibodies used in particular assay kits. Case presentation A 34 years old woman was admitted to the Endocrinology Research Centre in September 2021 with a diagnosis of hypothyroidism and diabetes mellitus. Upon admission she complained of high glycemia indexes up to a maximum of 34 mmol/l ( 612 mg/dl), high TSH and low free T4 ( fT4) concentrations, despite reporting regular levothyroxine administration at a dose of 200 mcg per day. Under nursing supervision, her fT4 was rapidly normalized suggesting non-compliance as the cause of low thyroid hormone milieu. Glycemic fluctuations from 33 to 2.1 mmol/l (594 to 38 mg/dl) according to glucometer measurements were observed against the background of Lis-Pro insulin therapy, while no hyperglycemia was registered in venous blood and in the interstitial fluid concomitantly with the values found by glucometer. It was assumed that the patient’s fingers were intentionally contaminated with glucose solution. Factitious hypo- and hyperglycemia were suspected. During yet another episode of hypoglycemia (1.86 mmol/L, 33 mg/dl) venous blood was drawn. Low to low-normal insulin and C-peptide values were found: 2.2 µU/ml (Roche kit) and 1.18 ng/ml, respectively. Therefore, insulin concentration in the same sample was re-tested with another kit (Abbott) and a significantly elevated value of 89.9 µU/ml was detected. Based on these results, FH was confirmed due to exogenous administration of an insulin analog undetectable by the Roche kit. Conclusion This clinical example illustrates to draw attention to multiple manipulations employed by subjects with Munchhausen Syndrome. In addition, this diagnosis may be further complicated by the laboratory use of immunoassay kits incapable of detecting some insulin analogs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism

Yukina

Katsobashvili

Platonova

et al. 2022

Clin Diabetes Endocrinol

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“…9 During laboratory research, exogenous injection of human insulin is characterized by high levels of this hormone, as well as suppression of C-peptide and proinsulin. 10 However, in cases of surreptitious injection of insulin analogs, many authors 2,[11][12][13] reported the low level of detected insulin. Some experts have linked these cases to low cross-reactivity of several types of immunoassay with insulin analogs.…”

Section: Introductionmentioning

confidence: 99%

“…Some experts have linked these cases to low cross-reactivity of several types of immunoassay with insulin analogs. 2,11,12,[14][15][16][17] This is due to differences in immunoreactivity of insulin analogs and human insulin because of amino acid sequence changing in the C-terminal part of the B-chain. 11 Moreover, changing of only 1 amino acid can highly decrease the ability of some analyzers to observe this preparation.…”

Section: Introductionmentioning

confidence: 99%

Clinical Case of Surreptitious Hypoglycemia Due to Deliberate Insulin Analog Administration

Yukina

Nuralieva

Трошина

et al. 2021

Clin Med Insights Case Rep

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Hypoglycemic syndrome is a life-threatening condition that can lead to hypoglycemic coma and death. Surreptitious hypoglycemic syndrome is the deliberate use of insulin preparations or oral hypoglycemic drugs aimed to reduce blood glucose level. If human insulin is injected, high level of immunoreactive insulin (IRI) and low level of C-peptide at the moment of hypoglycemia are always detected. However, the fact of deliberate administration of insulin analogs is difficult to prove. In these cases if insulin kit test with low cross-reactivity with insulin analogs is used, the low levels of IRI and C-peptide will be suspected. Some experts suggest the presence of cross reactivity with analogs of insulin in a number of commercial kits, which makes it possible to detect cases of surreptitious hypoglycemia. We present a clinical case of a patient with surreptitious hypoglycemia due to the administration of insulin analogs and discuss the problems of its laboratory diagnosis.

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Clinical Interpretation of Analytical Results

2020

Fundamentals of Analytical Toxicology

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Interpreting insulin immunoassays during investigation of apparent spontaneous hypoglycaemia and insulin overdose

Cited by 9 publications

References 12 publications

Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism

Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism

Clinical Case of Surreptitious Hypoglycemia Due to Deliberate Insulin Analog Administration

Clinical Interpretation of Analytical Results

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