Clinical Chemistry Podcast

Studies have found that drugs are now so prevalent that over 10% of a population were found to have traces of Class A drugs on their fingerprints despite never using any of those drugs. While fingerprints have been suggested as a possible sample to rapidly and noninvasively carry out drug testing, identifying drug users and not those who may have passively encountered a drug can be complex. In a study published in the June 2018 issue of Clinical Chemistry and available online now, researchers from the University of Surrey together with Dutch scientists may have found a solution. They present evidence that their techniques give a zero false positive rate in the fingerprints from drug-free volunteers. Yet, they were able to detect 87.5% of the cocaine users and 100% of heroin users.

Familial hypercholesterolemia is a frequent genetic disorder encountered in clinical practice and is associated with high levels of serum LDL cholesterol known as the "bad cholesterol." A diagnosis of familial hypercholesterolemia has important clinical implications with respect to risk of cardiovascular disease and a requirement for intensive pharmacological therapy. Often, the baseline LDL cholesterol before treatment is not available because the patient has initiated and continues on lipid lowering therapy, especially statins. Furthermore, the original baseline LDL cholesterol may predate the current status by many years and cannot be easily retrieved. The February 2018 issue of Clinical Chemistry published a paper describing a method to obtain an imputed, or estimated, baseline LDL cholesterol concentration in these patients who are already taking cholesterol lowering drugs. Both a computer program and a smartphone app are available from links in the paper. We are pleased to have the lead author of that paper as a guest on this podcast. Isabelle Ruel is a Clinical Biochemist at the Research Institute of the McGill University Health Center Royal Victoria Hospital in Montreal, Quebec, and is currently the national coordinator of the Canadian Registry on Familial Hypercholesterolemia.

A paper in the March 2018 issue of Clinical Chemistry describes a liquid chromatography tandem mass spectrometry procedure for multi-steroid profiling in Cushing syndrome and other disorders. The lead author of that study is Dr. Graeme Eisenhofer, who is professor and the Chief of the Division of Clinical Neurochemistry at the Institute for Clinical Chemistry and Laboratory Medicine at the Technical University in Dresden, Germany. He is our guest in this podcast.

Commutability is an important concept in determining traceability and the relationship among different methods that are used to measure the same analyte but just how to describe and classify commutable materials is not always straightforward. The March 2018 issue of Clinical Chemistry published a series of three reports from the Working Group on Commutability of the International Federation of Clinical Chemistry and Laboratory Medicine, or IFCC, that describe recommendations for assessing commutability.

Normal pregnancy is associated with profound hormonal and metabolic changes in the mother, including changes in thyroid hormones. These normal changes include increased thyroid binding globulin, increased total T3 and total T4, transient decrease in TSH, and in some patients, a transient increase in serum FT4 during the first trimester. In 2017, the American Thyroid Association issued new guidelines for the diagnosis and management of thyroid diseases during pregnancy, which can be difficult due to the numerous normal physiological changes. Most would agree that the document is an excellent review of current literature relating to the assessment of thyroid status during pregnancy. However, one researcher wonders if a particular recommendation of the document is misguided.

Expert Q&A

In the era of precision medicine, it is no surprise that there is an emerging interest in personalizing one's diet based on their genetic make-up. This concept called, "precision nutrition," refers to the application of -omics techniques such as genomics and metabolomics, to achieve better prevention or treatment of disease to optimize nutrition. The January 2017 Clinical Chemistry special issue on obesity includes a review article that summarizes the current and future roles of nutritional metabolomics.

Although bariatric surgery techniques were originally developed to treat morbid obesity, the indications for their use have expanded as a consequence of the emerging evidence of their wider metabolic benefits. Now described as metabolic surgeries, these treatment methods derive as much benefit from their metabolic and cardiovascular effects as from the resulting weight reduction. Though promising evidence is emerging, there is a need for further mechanistic studies to assess the true potential of metabolic surgery to treat the myriad other disorders of metabolism and to better understand their consequences in terms of cardiovascular disease and cancer risk reduction. Additionally, there may be unintended consequences of bariatric surgery that are related to long term adverse skeletal effects and nutritional deficiencies.

Hepatitis C virus or HCV infection affects close to 150 million people worldwide. In the U.S., it is estimated that as many as five million people have been infected with the Hepatitis C virus, many of whom are unaware of their infection. HCV is now the most common indication for liver transplantation, and it accounts for more deaths each year than all other reportable infectious diseases combined including HIV. Advances in testing methods and antiviral therapies with increased development of infrastructures that improve access care now make eradication of HCV infection in well-resourced countries a realistic goal. However, challenges in implementing screening programs and continues evolution of assay methods and screening protocols raise several issues for how clinicians and laboratories respond to the changing landscape for HCV diagnosis and treatment. The December 2017 issue of Clinical Chemistry includes a Q&A article with several experts who offer their insights and opinions on this topic.

Adrenal steroid analysis plays an important role in the diagnosis of Cushing's syndrome, disorders of steroidogenesis, and adrenal tumors. The analytical sensitivity and specificity for steroid assays have evolved over time from individual immunoassays to multiplexed mass spectrometry-based methods. This transition has highlighted a need for simultaneous measurement of multiple steroids and their various metabolites to achieve the best diagnostic accuracy. Therefore, metabolomic profiling performed by liquid chromatography, high-resolution accurate-mass mass spectrometry might be poised to make a substantial impact on endocrine laboratory testing. The December 2017 Issue of Clinical Chemistry describes such a method used to determine sex- and age-based reference intervals and to perform a limited assay evaluation in patients with different adrenal diseases.