Sensitive and specific laboratory tests and imaging studies are essential to accurate diagnosis in many clinical settings. Proper use of the laboratory and imaging requires accurate clinical hypotheses generated at the bedside. Laboratory tests and imaging provide reliable and valid answers to well-conceived clinical questions. They are also liable to overinterpretation and can be quite misleading if not interpreted in the clinical context as answers to specific questions. Beyond a few screening tests, these studies should be used to test the physiologic and diagnostic hypotheses generated during the history and physical exam. The laboratory and the radiology suite are not the places to look for ideas; they are the places to test hypotheses. If you are unable to generate testable hypotheses after the history, physical exam, and screening tests, it will be more useful to seek consultation than to begin an undirected series of laboratory and radiologic studies. A full discussion of the proper use of diagnostic tests is beyond the scope of this text.
PRINCIPLES OF LABORATORY TESTING
Laboratory testing is principally done for two reasons: (1) to obtain information that cannot be determined clinically, but which is often important in forming hypotheses and (2) to test hypotheses. Tests in the first category are commonly described as “routine” testing and include serum electrolytes, blood urea nitrogen, creatinine, complete blood counts, urinalysis, and, less commonly, transaminases and erythrocyte sedimentation rate or C-reactive protein. Some, or all, of these tests are performed in patients with significant illness to help the clinician identify significant abnormalities in major organ function or laboratory signs of inflammation or infection. Tests in the second category are innumerable. They are used to identify specific abnormalities and diseases. The diagnostic performance of these tests is dependent upon the patient population tested. Tests in this category are most useful when the diagnosis in question is in the mid-range of probability, roughly 20%–80%. To understand why this is so, it is necessary to understand the measures of test performance and how interpretation is dependent on both the diagnostic criteria for a disease or condition and the pretest probability that the disease is present.
Principles of Testing for Disease
Disease present or absent
How do we determine who has the disease and who does not? This is done with an independent test or set of criteria accepted as establishing “the diagnosis.” The assumption is that a disease is either present or absent. Although this may seem obvious for diseases such as cancer or an infection where a tissue biopsy or culture are the diagnostic standards, most biologic measurements are continuous variables, not either/or determinations; it is often difficult to say whether rheumatoid arthritis is present or not, or which level of creatinine determines renal failure. Most diseases have variable clinical severity; hence the diagnostic standard used to establish the disease can ...