This article discusses the most common causes of raised alkaline phosphatase levels in an asymptomatic patient and provides advice on the relevant investigations.

Chronic diarrhoea is common and mostly due to diarrhoea predominant irritable bowel syndrome. Diarrhoea predominant irritable bowel syndrome affects about 11% of the population; however, up to a third of these patients actually have bile acid diarrhoea. There are, therefore, more than one million sufferers of bile acid diarrhoea in the UK. Bile acid diarrhoea is caused by small bowel malabsorption of bile acids and the increased bile acids in the large intestine cause diarrhoea. Once diagnosed, the treatment of bile acid diarrhoea is simple and effective. Bile acid diarrhoea , however, is often not diagnosed because of a lack of easily available and reliable diagnostic methods. In the United Kingdom, the radiolabelled 23-seleno-25-homotaurocholic acid test is the gold-standard method of diagnosis. 23-seleno-25-homotaurocholic acid test, however, is expensive, inconvenient to the patient, involves radiation exposure and has limited availability. As such, a laboratory biomarker is desirable. This review briefly discusses the pathophysiology and management of bile acid diarrhoea and critically evaluates methods for its diagnosis, including serum 7α-hydroxy-4-cholesten-3-one, faecal bile acid measurement, serum fibroblast growth factor 19, urine-2-propanol, and the 14C-glycocholate breath and stool test.

Background: Biotin interference in biotin-streptavidin-based immunoassays is increasingly reported due to individuals taking biotin-containing supplements and patients prescribed biotin. The reported prevalence of serum biotin above the lowest threshold (≥10 µg/L) for interference in Roche Diagnostics immunoassay tests is 0.8% in Australia and 7.4% in the USA. There are, however, no such data in UK populations. In a service evaluation, we therefore studied the prevalence of biotin interference in routine serum samples received in our laboratory. Methods: Biotin was measured in 524 anonymized surplus serum samples in which at least one immunoassay test had been requested. Results: The median (95% confidence intervals) for serum biotin was 0.27 µg/L (0.07–0.93 µg/L). Serum biotin was <10 µg/L in all samples, <5 µg/L in 522 (99.6%) and <1 µg/L in 513 (98.1%) samples. In four samples, serum biotin was ≥2.5 µg/L (0.8%). Conclusions: These data indicate that the probability of biotin immunoassay interference in our patient population is extremely low, with the exception of assays reporting the lowest interference thresholds (e.g. Ortho Troponin I assay [threshold ≥2.5 µg/L]).

Background: The widely accepted practice of not reporting any results from ethylenediaminetetraacetic acid (EDTA) contaminated samples necessitates repeat phlebotomy and could delay clinical management decisions. EDTA, however, interferes variably or not at all in assays. EDTA concentration in contaminated samples, like serum indices, therefore, could be used to selectively report the result of analytes not affected at measured EDTA concentration. Methods: A serum pool, level 1 and level 3 internal quality control materials were spiked with tripotassium-EDTA to create samples with EDTA concentration up to 6.0 mmol/L. EDTA and 45 common and critically important analytes were measured on Abbott Architect to identify EDTA concentrations for analytes where the change in concentration exceeded their respective reference change value (RCV) for unidirectional change at 95% probability. Results: Serum potassium increased and calcium decreased exceeding RCV at 0.17 mmol/L EDTA. Alkaline phosphatase (ALP) decreased exceeding RCV at EDTA >1.86 mmol/L. The decrease in iron did not exceed a wide RCV of 61.9% until maximum spiked EDTA but exceeded the desirable specification for allowable total error (30.7%) at EDTA >1.86 mmol/L. The small decrease in magnesium did not exceed RCV. EDTA up to the concentration in blood collection tubes did not affect the results of any other measured analyte. Conclusions: Only serum potassium, calcium, ALP and iron studies, of the 45 analytes studied, should not be reported in EDTA contaminated samples. EDTA concentration cut-offs for selective reporting would further facilitate reporting of these analytes in EDTA contaminated samples.

Although adult spontaneous (non-diabetic) hypoglycaemia is rare, its recognition is important for the preventative or curative treatment of the underlying cause. Establishing Whipple’s triad—low blood glucose, neuroglycopaenia and resolution of neuroglycopaenia on increasing blood glucose levels to normal or above—is essential to verify hypoglycaemia. Awareness that hypoglycaemia may occur in severely ill patients is important for its prevention. Further investigation in such cases is unnecessary unless another cause of hypoglycaemia is suspected. Patients are often asymptomatic and normoglycaemic at review. Their history of medication, self-medication, access to hypoglycaemic drugs, alcohol use and comorbidity may provide aetiological clues. The investigation involves obtaining blood samples during symptoms for laboratory glucose measurement or provoking fasting or postprandial hypoglycaemia as directed by symptoms. If confirmed, insulin, c-peptide, proinsulin and beta-hydroxybutyrate are analysed in hypoglycaemic samples. These will classify hypoglycaemia due to non-ketotic hyperinsulinaemia, non-ketotic hypoinsulinaemia and ketotic hypoinsulinaemia, and direct investigations to identify the underlying cause. There are, however, many pitfalls that may mislabel healthy individuals as “hypoglycaemic” or misdiagnose treatable or preventable causes of spontaneous hypoglycaemia. Clinical acumen and appropriate investigations will mostly identify hypoglycaemia and its cause.