Cross-reactivity in assays for prolactin and optimum screening policy for macroprolactinaemia.

Objectives: Macroprolactin cross-reacts in immunoassays for prolactin causing apparent hyperprolactinaemia (macroprolactinaemia) and consequent misdiagnosis and mismanagement of patients.

Methods: We determined the prevalence of macroprolactinaemia using prolactin immunoassays with reported "high" (Tosoh) or "low" cross-reactivity (Roche) with macroprolactin. We additionally modelled the effects of increasing the screening threshold on workload and sensitivity in the detection of macroprolactinaemia.

Interference by macroprolactin in assays for prolactin: will the Diagnostics Regulation lead to a solution at last?

Cross reactivity with high molecular weight complexes of prolactin known as macroprolactin is a common cause of positive interference in assays for serum prolactin. All prolactin assays currently available are affected with 5-25% of results indicating hyperprolactinaemia falsely elevated due to macroprolactinaemia - hyperprolactinaemia due to macroprolactin with normal concentrations of bioactive monomeric prolactin. Macroprolactinaemia has no pathological significance but, if it is not recognised as the cause, the apparent hyperprolactinaemia can lead to clinical confusion, unnecessary further investigations, inappropriate treatment and waste of healthcare resources.

Macroprolactinemia Detection by Magnetically Assisted Polyethylene Glycol Precipitation: Potential for Automation.

Background: Macroprolactin is an immunoglobulin-prolactin complex that is not bioactive in vivo but the prolactin component remains immunoreactive. The complex is a universal source of interference in prolactin immunoassays and commonly results in misdiagnosis of hyperprolactinemia with consequent clinical mismanagement of patients. Removal of macroprolactin by precipitation with polyethylene glycol (PEG) is an effective technique for identifying such patients but unfortunately not universally employed due to the manual nature of the procedure.

Determination of prolactin: the macroprolactin problem.

Serum prolactin is frequently measured when investigating patients with reproductive disorders and elevated concentrations are found in up to 17% of such cases. Clinical laboratories rely predominantly on automated analysers to quantify prolactin levels using sandwich immunometric methodologies. Though generally robust and reliable, such immunoassays are susceptible to interference from a high molecular mass prolactin/IgG autoantibody complex termed macroprolactin.

Clinical observations on the significance of raised cardiac troponin-T in patients with myositis of varying etiologies seen in rheumatology practice.

To study the source and clinical relevance of elevated cardiac troponin-T (cTnT) in patients with inflammatory myositis of varying etiology is the objective of this study. Patients with new-onset myositis of varying etiologies and raised serum cTnT and creatine kinase (CK) were identified. Clinical myocardial disease was ruled out on the basis of history, examination, ECG, and 2D-echocardiography.

Immunoglobulin interference in serum follicle-stimulating hormone assays: autoimmune and heterophilic antibody interference.

Interference in immunoassay caused by endogenous immunoglobulin is a cause of incorrect laboratory results that can drastically affect patient management. Two cases of immunoglobulin interference in serum follicle-stimulating hormone (FSH) assays are presented. These cases illustrate two common mechanisms for false-positive interference in two-site (sandwich) immunoassays.

Circulating immunoreactive cardiac troponin forms determined by gel filtration chromatography after acute myocardial infarction.

Background: Cardiac troponin I (cTnI) and cTnT measurements are used in the diagnosis of acute myocardial infarction (AMI). Together with troponin C (TnC), the cTnI and cTnT forms make up the ternary cTnT-cTnI-TnC (TIC) complex found within myocardium. Whether cTn occurs in the circulation after AMI as ternary TIC, binary cTnI-TnC (IC) complexes, or free troponin forms has not been thoroughly investigated.

An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations.

Objectives: To report detailed investigations in a case of elevated serum B(12) due to the presence of an IgG-B(12) complex, to determine the prevalence of this phenomenon and to review the literature.

Design And Methods: 431 samples with elevated B(12) (median 1250 ng/L, range 901-114,480 ng/L) were treated with polyethylene glycol to precipitate immunoglobulin complexes. Samples with >50% of precipitable B(12) (PPB(12)) were further investigated by protein G adsorption, gel filtration chromatography and measurement of B(12) on different analytical platforms.

Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms.

Background: Macroprolactin is an important source of immunoassay interference that commonly leads to misdiagnosis and mismanagement of hyperprolactinemic patients. We used the predominant immunoassay platforms for prolactin to assay serum samples treated with polyethylene glycol (PEG) and establish and validate reference intervals for total and monomeric prolactin.

Methods: We used the Architect (Abbott), ADVIA Centaur and Immulite (Siemens Diagnostics), Access (Beckman Coulter), Elecsys (Roche Diagnostics), and AIA (Tosoh) analyzers with samples from healthy males (n = 53) and females (n = 93) to derive parametric reference intervals for total and post-PEG monomeric prolactin.

A paediatric case of macro aspartate aminotransferase.

Macroenzymes are enzymes in plasma that have a higher molecular mass than the corresponding enzyme normally present under (patho) physiological conditions. Macro species have been described for most routinely measured enzymes, but with only a few reports of macro species with aspartate aminotransferase (AST), and in particular very few reports in children and adolescents. Routine biochemical analysis in a 15-year-old girl presenting with lower back pain revealed an isolated raised AST as part of a liver function test profile.

False-positive polyethylene glycol precipitation tests for macroprolactin due to increased serum globulins.

Background: The polyethylene glycol (PEG) precipitation test is widely used to detect hyperprolactinaemia caused by macroprolactin. We report two cases of hyperprolactinaemia in which a low recovery of serum prolactin (PRL) after PEG precipitation indicated the presence of macroprolactin, but no macroprolactin was detected by gel filtration chromatography (GFC). Both cases had elevated concentrations of serum globulin (IgG myeloma and polyclonal hypergammaglobulinaemia due to human immunodeficiency virus [HIV] infection), which prompted us to investigate further the effect of serum globulin on the specificity of the PEG precipitation procedure.

What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid haemorrhage in computed tomography-negative patients?

Background: Spectrophotometry of cerebrospinal fluid (CSF) for bilirubin is the recommended method for investigation in suspected cases of subarachnoid haemorrhage (SAH), when a computed tomography (CT) of the head is negative for blood. There is a potential need for a simpler alternative. Measurement of CSF ferritin might fulfil this need.

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol.

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG).

National audit of cerebrospinal fluid testing.

Background: UK National External Quality Assessment Service (NEQAS) Specialist Advisory Group for EQA of CSF Proteins and Biochemistry was interested in current practice for the biochemical investigation of cerebrospinal fluid (CSF) in the UK.

Methods: A questionnaire was sent to laboratories via regional audit committees and the results collated.

Results: Most laboratories were analysing CSF in a satisfactory manner.

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol.

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG).

Prevalence of increased serum creatine kinase activity due to macro-creatine kinase and experience of screening programmes in district general hospitals.

Background: Macro creatine kinase type 1 (MCK1) may be the cause of elevated total serum CK activity, which can lead to diagnostic confusion. There is evidence that this problem is poorly recognized perhaps due to a lack of information on its prevalence. Precipitation with polyethylene glycol (PEG) has been described for the detection of MCK1 but has not been fully evaluated.

Pseudo-pseudohypercalcaemia, apparent primary hyperparathyroidism and Waldenström's macroglobulinaemia.

An apparent primary hyperparathyroidism was reported due to pseudo-pseudohypercalcaemia in a 74-year-old man with Waldenström's macroglobulinaemia. It is important to recognise artificially elevated serum calcium levels so as to avoid erroneous diagnosis, unnecessary investigations and potentially inappropriate treatment.

Hypoglycemia due to an insulin binding antibody in a patient with an IgA-kappa myeloma.

Context: Autoantibodies to insulin have been described to cause spontaneous hypoglycemia in nondiabetic subjects. There have been occasional reports of spontaneous hypoglycemia due to monoclonal anti-insulin antibodies. We present the first report of a patient with an IgA-kappa myeloma in whom frequent hypoglycemia resulted from the ability of the monoclonal IgA-kappa to bind insulin.