Diagnosis Of Factitious Hypoglycemia Research Articles

HPLC-MS/MS in the diagnosis of factitious hypoglycemia: A case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pitfalls in Diagnosing Hypoglycemia Due to Exogenous Insulin: Validation and Utility of an Insulin Analog Assay

ObjectiveTo overcome the limitations of commercially available insulin immunoassays which have variable detection of analog insulin and can lead to clinically discordant results and misdiagnosis in the workup of factitious hypoglycemia. Patients and MethodsWe performed analytical validation of a liquid chromatography high resolution accurate mass (LC-HRAM) immunoassay to detect insulin analogs. We completed clinical assessment using a large cohort of human serum samples from 78 unique individuals, and subsequently used the assay in the evaluation of eight individuals with high diagnostic suspicion for factitious hypoglycemia. ResultsThe performance characteristics show that the LC-HRAM immunoassay can be applied to detect five commonly used synthetic insulin analogs (lispro, glulisine, aspart, glargine metabolite, and detemir) in human serum. Our clinical cases show that this assay could be used in the diagnosis of factitious hypoglycemia by identifying the analog insulin(s) in question. ConclusionThe LC-HRAM immunoassay reported here overcomes a gap in our diagnostic pathway for hypoglycemia. The results obtained from our studies suggest that this method is appropriate for use in clinical laboratories when factitious hypoglycemia is considered as a differential diagnosis.

Clinical case of factitious hypoglycemia

Hypoglycemic syndrome (HGS) is a significant decrease glucose in blood, manifested by neurological symptoms, and stopped by the introduction of glucose. Among the many causes of HGS the special place is taken by the factitious hypoglycemia, as one of the variants of Munchausen syndrome. Hypoglycemia in such cases is achieved by the intentional introduction of hypoglycemic drugs. The most commonly used medications are sulfonylurea derivatives, which are affordable, inexpensive and legal. The close collaboration of clinicians with the laboratory service plays a key role in the diagnosis of factitious hypoglycemia. Since the results of biochemical and hormonal analyzes in patients with hypoglycemia due to reception of oral hypoglycemic medications and pancreatogenous HGS are identical, the only way to differentiate these conditions is by detection of insulin secretagogue substances in the blood (or urine).The determination of oral hypoglycemic medications in cases of suspicion of artificial reception is not implemented in Russia. Factitious hypoglycemia in most cases is the diagnosis of exclusion, and its confirmation if often based on detection of medications among the personal effects of patient. This is a significant difficulty given the ethical standards. However, since 2018 we conduct in our Centre the determination of 7 oral hypoglycemic medications (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in patient’s blood using the liquid chromatography–tandem mass spectrometry (LC-MS). This article presents a clinical case of a patient without diabetes mellitus taking glibenclamide and detection of this drug using highly selective LC-MS.

P-237 - Life-threatening factitious hypoglycemia: a case report and review

Although fundamentally a psychiatric disorder, factitious disorder challenges physicians of any specialty as it might simulate a wide variety of medical conditions. Insulin or sulfonylurea-induced hypoglycemia, in particular, might mimic insulinoma. To examine the risk factors, to highlight the diagnostic difficulties and to discuss the management options for factitious hypoglycemia. A case report. A twenty-nine-year-old was admitted at the endocrinology department for recurrent episodes of “spontaneous” hypoglycemia resulting in several seizures and even in a deep coma state. Investigations concluded that the patient had factitious hypoglycemia due to surreptitious insulin and glibenclamide use. She was referred to the psychiatric outpatient clinic for examination and management. Psychiatric interview found no associated axis I disorder. Treatment included olanzapine along with psychotherapy. Diagnosis of factitious hypoglycemia is often a daunting task, management remains difficult and long-term prognosis is unpredictable. Close cooperation between endocrinologists and psychiatrists can further clarify the diagnosis and help optimize the treatment.

Caractéristiques immuno-analytiques du peptide-C

The C-peptide is a polypeptide of connection that is generated during the proteolytic cleavage of proinsulin in pancreatic beta cells. It is secreted in equimolar amounts with insulin. Unlike insulin, C-peptide is not metabolized by the liver but filtered by the kidneys and excreted in the urine. Because of its longer half-life (compared with insulin), the C-peptide value is better suited to control the secretion of β cells. The C-peptide plays an important role in the structural conformation of A and B chains of insulin and the formation of two disulfide bonds present in the proinsulin molecule that are conserved in the active insulin. The main indications of its assay are: evaluating the residual function of β cells in diabetic patients and in case of exogenous insulin substitution, the evaluation of secretory capacity of β cells in the early stage of diabetes mellitus, control of patients with symptoms of hypoglycemia. Less frequently, the assay may be useful in patients suffering from polycystic ovarian syndrome, the diagnosis of insulinoma, the diagnosis of factitious hypoglycemia, the evaluation of β-cell transplantation and monitoring of patients after pancreatectomy. The urinary assay facilitates the monitoring of gestational diabetes and the follow-up of patients with unstable glycemic status. Besides structural and physiological C-peptide data, this paper points out the optimal conditions for immunoassay and interpretation of results. Le peptide-C est un polypeptide de connexion qui est formé lors du clivage protéolytique de la pro-insuline dans les cellules béta pancréatiques. Il est sécrété en quantité équimolaire avec l’insuline. Contrairement à l’insuline, le peptide-C n’est pas métabolisé par le foie mais filtré par les reins et éliminé dans les urines. À cause de sa demi-vie plus longue que celle de l’insuline, la détermination du peptide-C est mieux adaptée pour contrôler les sécrétions des cellules β. Le peptide-C joue un rôle important dans la conformation structurelle des chaînes A et B de l’insuline et la formation des deux ponts disulfure présents dans la molécule de pro-insuline qui sont conservés dans celle de l’insuline active. Les principales indications du dosage sont : l’évaluation de la fonction résiduelle des cellules β chez les patients diabétiques et en cas de substitution par l’insuline exogène, l’évaluation des capacités sécrétoires des cellules β dans le stade précoce de diabète sucré, le contrôle des patients avec symptômes d’hypoglycémie. Plus exceptionnellement, son dosage peut être utile chez les patientes affectées d’un syndrome des ovaires polykystiques, le diagnostic d’un insulinome, le diagnostic d’une hypoglycémie factice, l’évaluation d’une greffe des cellules β et pour la surveillance de patients après pancréatectomie. Le dosage urinaire facilite le suivi du diabète gestationnel et celui des patients en cas de situation glycémique instable. Après les caractéristiques structurales et physiologiques du peptide-C, cet article aborde les données pré-, per- et postanalytiques utiles pour l’interprétation des dosages.

Hypoglycemia Due to Surreptitious Injection of Insulin: Identification of Insulin Species by High-Performance Liquid Chromatography

To identify the circulating species of insulin after separation by high-performance liquid chromatography (HPLC) in patients with factitious hypoglycemia. In three of four patients presented, the diagnosis of surreptitious insulin injection was made by documenting the presence of animal insulin in the circulation after separation of the circulating insulin forms by HPLC. Animal insulin was identified. Thus, the identification of the circulating form of insulin in the circulation by HPLC may be a useful adjunct in the diagnosis of factitious hypoglycemia if animal insulin has been injected and if the simultaneously measured concentrations of insulin and C-peptide are inconclusive.