Abstract: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.Keywords: endogenous insulin antibodies; Hirata's disease, insulin autoimmune hypoglycaemia; hypoglycaemia in non-diabetic; insulin autoimmune syndrome (IAS); interference in immunoassays of insulin, proinsulin and C-peptide; wrong immunoassay results .
Gynaecomastia is the most common disorder of the male breast. It can occur at any age, and for this reason laboratory investigations may be requested by clinicians from many specialties. Gynaecomastia may occur transiently in neonates. It may also occur transiently during puberty, when it is common and generally benign. It must, however, be regarded as unusual in prepubertal children and all young and middle-aged men. Although iatrogenic and benign gynaecomastia are common in the elderly, further investigations may still be justi®ed since breast cancer or other neoplasm must be ruled out. Biochemical investigations, when warranted, are aimed at establishing an underlying cause. Endocrine investigations might include serum oestradiol (or oestrone if available), testosterone, luteinizing hormone, sex-hormone-binding globulin, human chorionic gonadotrophin, prolactin and thyroid function tests. In this review, the source and role of oestrogens in men, the androgen±oestrogen dynamics, the causes and clinical entities of gynaecomastia, and interpretation of laboratory tests are described.
The presence of antibodies in some patients' serum has long been known to be a potential source of interference in immunoassays, as shown by numerous case reports. These often appear after the introduction of a new analyte (e.g. troponin) and then decrease in number as the topic becomes exhausted. This highlights the persistent and intrinsic nature of this problem, despite attempts by the manufacturers to compensate for this source of error. However, an explanation of the immunoanalytical basis underpinning these assays could be more effective in raising awareness than intermittent case reports. In this review we have outlined the use of antibodies as reagents, the factors determining how they bind to antigen(s), and the nature of the immune response in order to explain the insidious and unpredictable nature of this form of interference. Studies on the prevalence of interference have yielded values ranging from 0.05 to more than 2%. However, these figures are analyte- and assay-specific, influenced by the study design, and are not therefore generally applicable. It is also highly likely that figures on prevalence and incidence will worsen in the future because of the wider use of monoclonal antibodies as diagnostic and therapeutic tools. Clinical laboratories should be alert to assay interference from antibodies irrespective of its nature, as immunoassays will remain an indispensable analytical tool, unlikely to be replaced in the foreseeable future by a practical alternative.
Full automation of laboratory procedures confers numerous advantages over semi-automated/manual tests because equipment, reagents and the computation of results are offered as an integrated package. Automation has allowed millions of immunoassay tests to be performed with good sensitivity and excellent precision but inaccuracy caused by interference from endogenous immunoglobulins/antibodies remained a problem (irrespective of the immunoassay's format). Interference leading to a falsely high or low result affects a specific sample and may not be obvious despite the strictest laboratory control schemes. Reporting and interpreting such potentially erroneous data remained however the responsibility of the clinical laboratory despite the limited information supplied by their providers. The focus of this review is on highlighting the potential downside of current disjointed and blurred arrangement between the developers/providers of immunoassays, and the laboratorians responsible for providing these data to their clinical colleagues. These limitations can be addressed by drawing attention to the importance of the key fundamentals underpinning these immunologically based analyses which, if carefully considered, could help to formulate pragmatic strategies to reduce errors in immunoassays. In this review, the inherent fallibility of the binding reaction between an antigen and antibody will be reiterated. The difficulties in defining reaction rate kinetics in non-equilibrium automated assays, the potential clinical error rate and the need for minimising analytical error rate of these automated technologies will be highlighted.
Background: Immunoassays are used in almost all medical and surgical specialties, but they suffer from interference from proteins such as antibodies in some patients’ sera. Such interferences are usually reported in the literature only as case reports after the introduction of a new assay. Methods: We undertook a prospective observational study on 5310 patients for whom the common immunoassay tests for thyroid-stimulating hormone (TSH) and/or gonadotropins were requested. All TSH and gonadotropin results were critically assessed for a mismatch between the clinical details and analytical results to identify samples suspected of analytical unreliability. These were tested further by three approaches to screen for interference. Results: From the 5310 sets of results, 59 patients’ samples were identified as suspect and were tested further. Analytically incorrect results were found in 28 (0.53% of the total studied). The magnitude of interference varied, but in 23 of 28 patients (82%), it was considered large enough to have a potentially adverse effect on cost and/or the clinical care of these patients. Two cases, described in detail, illustrate the adverse effect of error on patient care and cost, and the second highlights the difficulties and limitations of current approaches for identifying interference and inaccuracy in immunoassays. Conclusions: Because millions of TSH/gonadotropin tests are carried out in UK hospital laboratories alone, our data suggest that thousands of patients could be adversely affected by errors from interferences. Early identification of interference in cases with unusual results could be valuable.
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