Endocrine Biomarkers

Clinicians and Clinical Chemists in Partnership

Hossein Sadrzadeh, Gregory Kline, Hossein Sadrzadeh, Gregory Kline

• Publisher: Elsevier
• Year: 2017
• ISBN:
  9780128034187
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

Endocrine Biomarkers: Clinical Aspects and Laboratory Determination covers all the pre-analytical variables that can affect test results, both in the clinic and laboratory. Biomarkers of endocrine and bone diseases are discussed from both clinical and laboratory perspectives, and the authors elaborate on the teamwork-based app+roach between the clinician and the laboratory professional in the diagnosis and management of endocrine and bone disorders.

Discussions include test utilization, laboratory measurement methods, harmonization and standardization, interpretation of results, and reference intervals. Each chapter ends with a discussion of one or two relevant cases with shared opinions from both a clinician and a clinical chemist. Each chapter also includes a summary box outlining key points and common pitfalls in the use of specific disease biomarkers and tests.

• Focuses on the traditional, current, and emerging clinical chemistry tests for endocrine and bone diseases, along with their application in individual clinical management
• Presents a brief discussion of each disorder and its respective interrelationships, along with laboratory methodologies that can be used to aid in evaluation of disorders
• Reviews common approaches to the measurement of the relevant hormones, with a special focus on measures that require a structured clinical testing scenario
• Reviews novel chemistry tests as potential means of future diagnostic tests
• Provides an overview of the current methodology and controversies in the concept of target lipid levels, paying particular attention to the role of clinical chemistry in helping to implement population health targets

Chapter 1

Variables affecting endocrine tests results, errors prevention and mitigation

Hossein Sadrzadeh, PhD¹, Leland Baskin, MD² and Gregory Kline, MD³, ¹Professor, Department of Pathology and Laboratory Medicine, and Graduate Studies, University of Calgary and Section Chief of Clinical Biochemistry, Calgary Laboratory Services, Calgary, Alberta, Canada, ²Associate Professor, Department of Pathology and Laboratory Medicine, University of Calgary and VP of Medical Operations Calgary Laboratory Services, Calgary, Alberta, Canada, ³Clinical Professor, Department of Medicine, Division of Endocrinology, University of Calgary, Calgary, Alberta, Canada

Abstract

All the tests in clinical laboratories are susceptible to preanalytical variables that can affect test results before a specimen is even analyzed. These variables include physiologic or nonphysiologic in nature and include types of collection devices, stature of patient during the collection, diet, circadian rhythms, the environment where the specimen is collected, proper blood collection techniques, the effect of drugs that the individual takes, and others. In addition to preanalytical variables, there are analytical and postanalytical factors that can cause erroneous test results. Traditionally, immunoassays (IAs) have been the most commonly used laboratory analyses for endocrine evaluation. Like all laboratory tests, they are affected by the factors described above; however, because of the numerous configurations of IA, these effects occur in varying degrees and directions. Several methods and techniques have been developed to mitigate the interferences, which has led to the rise of liquid chromatography with tandem mass spectrometry as the state-of-the-art method for measuring hormones and other molecules found in very low concentrations in human specimens. Both clinical biochemists and clinicians should be familiar with these factors and consider them whenever a test result does not match the clinical picture. In addition the clinician who interprets the test result must be aware of each test’s reliability for both ruling in or ruling out the disease in question. Application of the test result to the detailed clinical assessment will permit the best overall use of the laboratory in medicine. This chapter describes all the above factors in details.

Keywords

Preanalytical variables; postanalytical variables; immunoassays; interferences; HAMA; biotin; chromatography; mass spectrometry; LC–MS/MS

Chapter Outline

1.1 Introduction 2

1.2 Preanalytical Variables 2

1.3 Analytical Variables 3

1.4 Postanalytical Variables 3

1.5 Complete Test Process 3

1.6 Preanalytical 4

1.6.1 Physician Visits and Test Ordering 4

1.6.2 Sites of Blood Collection 7

1.6.3 Blood Specimen Classifications 9

1.6.4 Blood Collection Tubes 12

1.6.5 Specimen Processing, Transfer, and Storage 19

1.7 Analytical 19

1.7.1 Important Issues in Immunoassays 21

1.8 Clinical Applications of Valid Laboratory Results 27

1.8.1 Consideration of Clinical Application of Results Should Precede Ordering the Test 27

1.8.2 Clinicians Should Seek Advice From Specialists Prior to Ordering Tests With Which They Are Unfamiliar 28

1.8.3 Test Sensitivity 28

1.8.4 Test Specificity and Sensitivity 29

1.8.5 Positive and Negative Predictive Values 31

1.8.6 Screening and Confirmatory Tests 34

1.8.7 Accuracy and Precision Applied to Clinical Decision Making Around Fixed Biochemical Targets or Thresholds 35

1.9 The Endocrinologist–Chemist Relationship 36

References 37

1.1 Introduction

To make no mistakes is not in the power of man; but from their errors and mistakes the wise and good learn wisdom for the future

Plutarch

Errors inevitably occur in life, from errors of transcription to errors in judgement, and human beings, like any other creature, are not immune from making or experiencing errors in all aspects of their everyday lives, including in their health care. Indeed the Institute of Medicine of the National Academies in its 1999 report entitled “To Err is Human: Building a Safer Health System” estimated that up to 98,000 patients per year in the United States die due to medical errors [1]. Although the number of people affected by medical errors has been questioned by Brennan [2], the important fact is that errors do occur and each year many patients are deleteriously affected. In the United States, it is estimated that 22.8 million individuals have experienced at least one medical error either personally or via a family member [1], with an annual cost of 17–29 billion dollars (USD) [3]. The United States Agency for Health Care Research and Quality estimates that medical errors are the eighth leading cause of death in the country, higher than cancer, AIDS, and motor vehicle accidents [1,4].

With more than 7 billion laboratory tests performed in the United States each year and a common belief that ~70% of medical decisions are based on laboratory results, it can be expected that laboratory test results are a significant contributor to medical errors. This belief is supported by considering both the numerous responsibilities of the laboratory and its continued emphasis on reducing errors to improve patient safety and reduce adverse events. The importance of these endeavors is a result of the belief that 50% of errors were due to failure to do the requested tests, 32% were failure to act appropriately on the results, and in general, more than 50% were related to avoidable delays in diagnosis [5]. Therefore the recognition and minimization of preanalytical, analytical, and postanalytical variables that can lead to erroneous results demonstrates that the generation of “accurate results” in the clinical laboratory does not simply depend on having an expensive test run on a state-of-the-art instrument.

1.2 Preanalytical Variables

Preanalytical variables impact the laboratory test result prior to the analysis of the specimen, including physiological (e.g., biological rhythms, gender, age, pregnancy, fasting, and nonfasting) and nonphysiological (e.g., specimen collection process, tube material/type, stoppers, separating gel, preservatives in collection tubes, specimen processing, effect of drugs patient is taking, patient posture, tourniquets, and hemolysis effect). These variables must be considered and their impacts should be completely understood by both the laboratory and clinical team. These preanalytical variables, when applicable, are discussed for different tests in their corresponding chapters.

1.3 Analytical Variables

Analytical factors are those affecting the results during the analysis of specimens and mostly depend on characteristic of a given method and instrument such as precision, accuracy, linearity, limit of detection, and its comparison to a reference method. All methods used for patient testing must be evaluated and verified according to the Clinical Laboratory Standard Institute (CLSI) guideline [6]. Discussion of analytical methods is beyond the scope of this chapter.

1.4 Postanalytical Variables

Postanalytical errors are mostly clerical in nature and can be significant when results are calculated and reported manually. These include reporting results for patients with the same first and last name, miscalculation (specifically when specimen requires dilution and dilution factors must be used to calculate results), and reading or writing errors due to dyslexia (e.g., “76” instead of “67”). It is a good idea that all the results generated from any manual method be checked by senior technologists before reporting.

Key Point

Errors occur on daily basis in clinical laboratories. Most errors occur due to preanalytical factors that affect test results before specimens are tested. Clinicians should be familiar with these errors.

1.5 Complete Test Process

To understand and prevent errors in laboratory testing, one should consider all stages of the testing process as indicated below:

1. Preanalytical

a. Physician visit and test ordering

b. Patient physiology

c. Patient specimen (collection, transport, storage)

2. Analytical

a. Sample preparation

b. Instrumentation

3. Postanalytical

a. Reporting of results

b. Physician action

In this chapter, we will focus on an area of preanalytical variables that is most susceptible to error which is the specimen collection. Specifically, we will talk about sites of blood collection, tubes, and appropriate anticoagulants that are used for proper blood collection and the factors that can impact these processes.

There are many publications on preanalytical variables and their effects on test results. The important one is a set of books written by Donald Young describing all preanalytical variables, including the effects of drugs and diseases on test results [7].

1.6 Preanalytical

The term “pre-analytical variables” refers to factors that affect patient results before the specimen is tested and contribute the most to laboratory error. As mentioned earlier, preanalytical variables can be of physiologic and nonphysiologic nature. Unfortunately, not much can be done to prevent the impact of physiological factors on the test results. Fortunately, nonphysiological factors that can occur at any point from the time of patient’s visit to a doctor to the final stages of specimen collection are mostly preventable. Therefore a thorough understanding of these factors by both the clinicians and laboratorians is of extreme importance for the collection of high-quality specimens and generating highly accurate results. Most of these preanalytical variables, when applicable, are discussed for different tests in their corresponding chapters.

1.6.1 Physician Visits and Test Ordering

A patient’s visit to their doctor’s office is the first step as the consultation and examination performed by the physician provides the basis for test selection. Preanalytical errors can occur at this point in the process if the physician’s examination of the patient is flawed or if the appropriate test(s) are not selected by the physician. If the physician is unsure of the criteria for test selection or how to interpret the results, undertaking a consultation with the laboratory’s medical staff can ensure the appropriateness of the ordered test(s).

1.6.1.1 Patient physiology

It is well established that most laboratory errors (48%–68%) are related to the preanalytical phase of testing [8]. Patient preparation is an additional preanalytical consideration that is highly susceptible to the introduction of errors. Fortunately, patient adherence to preparation instruction and the implementation of specific reference ranges can reduce the impact of some physiological variables on test results. The laboratory, however, has limited ability to prevent physiological variables su...