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Insulin autoimmune syndrome (IAS) is considered to be very rare in Caucasians. Understanding its pathophysiology is paramount in (a) appreciating its potential impact on analyses of pancreatic hormones and (b) explaining its highly variable clinical manifestations in non-diabetic, non-acutely ill patients with indeterminate hypoglycaemia. The underlying aetiology of IAS is the presence of variable affinity/avidity endogenous insulin antibodies in significant amounts. The two types of insulin antibodies namely antibodies which bind insulin and/ or proinsulin(s) and receptor antibodies (insulin mimetic) will be discussed. Their biochemical and immunological roles in causing hypoglycaemia will be highlighted. Clinical manifestations of IAS can vary from mild and transient to spontaneous, severe and protracted hypoglycaemia necessitating in extreme cases plasmapheresis for glycaemic control. Antibodies of IAS can interfere in pancreatic immunoassay tests causing erroneous and potentially misleading results. Thorough testing for endogenous insulin antibodies must be considered in the investigations of non-diabetic, non-acutely ill patients with indeterminate and/or unexplained hypoglycaemia. [ABSTRACT FROM AUTHOR]

Potassium and magnesium are important circulating cations and are predominantly intracellular elements. Only a small fraction of these elements is present in extracellular fluids including blood (∼1%). Measurement of the concentration of such small fractions in blood is commonly used to assess and reflect their body content levels. However, some of these measurements can be flawed and a failure to recognise the limitations of these tests may result in misdiagnosis and/or unnecessary follow-up investigations and/or expensive hospital admissions. The focus of this note is three-fold (a) to highlight and discuss separately the less appreciated pitfalls of potassium and magnesium measurements per se, (b) suggestions to identify and rectify these snags and to improve their clinical interpretation, and finally (c) to discuss briefly the clinical inter-relationship between these two predominantly most abundant intracellular cations without dwelling on details which are outside the scope of this note. [ABSTRACT FROM AUTHOR]

Background: A major use of serum magnesium measurements in clinical practice is to identify patients with deficiency. However, numerous studies have shown that magnesium deficiency is common and may be present in over 10% of hospitalized patients, as well as in the general population. An important cause for under diagnosis of deficiency is that serum magnesium, the most commonly used test, can be normal despite negative body stores. This article focuses on the limitations of “normal” magnesium results and highlights the importance of lifestyle or “modus vivendi” as a pragmatic means of identifying those individuals potentially at risk for negative body magnesium stores. Methods: Researched peer reviewed articles on magnesium published between 1990 and 2008 in MEDLINE and EMBASE, using database keywords “magnesium, deficiency, diagnosis, treatment and hypomagnesaemia”. Bibliographies of retrieved articles have been searched and followed. We have also performed a manual search of each individual issue in which most of these reports have appeared. Results: In 183 peer reviewed studies published from 1990 to 2008, magnesium deficiency was associated with increased prevalence and risk in 11 major conditions. Similarly, in 68 studies performed over the same period, magnesium deficiency was found to predict adverse events and a decreased risk of pathology was noted when supplementation or treatment was instituted. Conclusions: The perception that “normal” serum magnesium excludes deficiency is common among clinicians. This perception is probably enforced by the common laboratory practice of highlighting only abnormal results. A health warning is therefore warranted regarding potential misuse of “normal” serum magnesium because restoration of magnesium stores in deficient patients is simple, tolerable, inexpensive and can be clinically beneficial. Clin Chem Lab Med 2010;48:323–7. [ABSTRACT FROM AUTHOR]

The presence of high affinity/avidity endogenous insulin antibodies in significant amounts in non-diabetic individuals could uniquely be a double whammy. Clinically it could trigger pathology, namely hypoglycaemia, and analytically it could cause erroneous and potentially misleading results (i.e., falsely high or falsely low) in the key biochemical parameters essential in the differential diagnosis of this pathology, namely serum insulin, proinsulin and even C-peptide. The purpose of this paper is to highlight the clinical and analytical sequelae of endogenous insulin antibodies in (a) delaying or even confusing the differential diagnosis of unexpected/unexplained hypoglycaemia, and (b) interfering in some immunoassays of pancreatic hormones (commercial or in-house). [ABSTRACT FROM AUTHOR]

The clinical laboratory may perform additional test or tests to ascertain the integrity of immunoassay analyses when the results are in doubt. Doubling serial dilutions is one of these confirmatory tests. Doubling dilutions is a useful and informative test for detecting inaccuracy and potential interference from endogenous antibodies in immunoassays. Despite its technical simplicity, the science underpinning this test is highly complex. Appreciating such complexities could help in understanding the various outcomes of such tests from misleadingly inaccurate but virtually linear/parallel results, despite the presence of interfering antibodies in some immunoassays, to an array of non-linearity/non-parallelism synonymous with interference in others. A lack of parallelism/linearity could identify some 60% of samples with inaccurate and potentially misleading results caused by endogenous interfering antibodies. Assessing real-time binding kinetics using techniques such as non-linear regression analysis or linearised transformations such as the Scatchard plot could help in identifying more samples in which the doubling dilutions test remains linear and parallel. Clin Chem Lab Med 2007;45:851–4. [ABSTRACT FROM AUTHOR]