Life-threatening hyperkalaemia and multisystem toxicity following first-time exposure to cocaine

Cocaine is a drug notorious for its ability to adversely affect almost any organ in the body and cause a plethora of biochemical abnormalities secondary to its severe vasoconstrictive properties. These abnormalities are not exclusively seen in habitual users or cases of overdose, and may sometimes cause confusion as to the underlying pathology. We describe a case of a young female who presented to the Accident and Emergency department in the early hours of the morning complaining of muscle weakness following the inhalation of a small quantity of an ‘unknown substance’ the previous night. Investigations showed life-threatening hyperkalaemia with a potassium of 9.0 mmol/L, evidence of rhabdomyolysis, acute renal as well as liver failure, disseminated intravascular coagulopathy and a raised troponin of 7000 ng/L, which later peaked to 15,600 ng/L. Four days later, she became hypoxic as a result of adult respiratory distress syndrome with grossly abnormal chest X-ray appearances. Following intensive therapy, she made a dramatic recovery and was discharged from hospital 20 days from presentation. This case highlights the importance of biochemical profiling in patients presenting with possible drug use, even in the absence of significant symptoms. </jats:p

Challenges and benefits of endogenous steroid analysis by LC-MS/MS

Quantification of endogenous hormonal steroids and their precursors is essential for diagnosing a wide range of endocrine disorders. Historically, these analyses have been carried out using immunoassay, but such methods are problematic, especially for low-concentration analytes, due to assay interference by other endogenous steroids. MS offers improved specificity over immunoassay and can be highly sensitive. GC–MS, with use of stable isotopically labeled internal standards, is considered the ‘gold standard’ method for serum steroid analysis. GC–MS is the method of choice for profiling steroid metabolites in urine, but these techniques are not appropriate for routine use in clinical laboratories owing to a need for extensive sample preparation, as well as analytical expertise. LC–MS/MS compares well to GC–MS in terms of accuracy, precision and sensitivity, but allows simplified sample preparation. While most publications have featured only one or a limited number of steroids, we consider that steroid paneling (which we propose as the preferred term for multitargeted steroid analysis) has great potential to enable clinicians to make a definitive diagnosis. It is adaptable for use in a number of matrices, including serum, saliva and dried blood spots. However, LC–MS/MS-based steroid analysis is not straightforward, and understanding the chemical and analytical processes involved is essential for implementation of a robust clinical service. This article discusses specific challenges in the measurement of endogenous steroids using LC–MS/MS, and provides examples of the benefits it offers. </jats:p

An association between post-meal bile acid response and bone resorption in normal subjects

Background The mechanism surrounding bone suppression after a meal may involve several mediators, but is yet to be clarified. Bile acids (BA) function as signalling molecules in response to feeding, and may be directly involved in bone suppression acutely after a meal. The aim of this study was to test the hypothesis that BA are involved in the acute bone suppression observed after a meal. Methods A prospective study in which samples collected from volunteers fed a 400 Kcal test meal after an overnight fast were analysed for parathyroid hormone (PTH), BA, and carboxyterminal of type 1 collagen telopeptide (CTX). The study was carried out in 10 healthy male volunteers. Ethical approval was obtained from the Local Research and Ethics Committee at King's College Hospital. Results Total BA, glycine conjugated bile acids (GCBA), PTH and CTX showed a response to meal ingestion. There was a negative correlation between percentage change in PTH and CTX ( R2 = −0.82, P = 0.004), and between PTH and GCBA ( R2 = −0.39, P = 0.005). Conclusion This study demonstrated an association between GCBA and PTH suppression after a meal. The drop in PTH concentration after a meal may be responsible for the suppression of bone resorption as observed by the decrease in CTX concentration. </jats:sec

Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation

Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women. Thirty-six women were classified as low bone density as determined by a heel ultrasound scan and twenty women had normal bone density acting as 'controls'. Those with low bone density (LBD) were supplemented with oral Ca and vitamin D and were classified according to whether they were 'responders' or 'non-responders' according to biochemical results before and after therapy compared to controls receiving no supplementation. Metabolomic studies on serum and urine were done for the three groups at 0 and 3 months of therapy using NAIR spectroscopy with pattern recognition. The 'non-responder' group showed a higher frequency of polymorphisms in the ESR1 (codons 10 and 325) and VDR (Bsm1 and Tag1 compared with to the 'responders'. The wild-type genotype for Fok1 was more frequent in those with LBD (70%) compared with the control group (10%). Distinctive patterns of metabolites were displayed by NMR studies at baseline and 3 months of post-treatment, segregating responders from non-responders and controls. Identification of potential 'non-responders' to vitamin D and Ca, before therapy, based on a genomic and/or metabolomic profile would allow targeted selection of optimal therapy on an individual basis.</p