Cross-reactivity. There are 6 currently available immunoassays, all of which use competitive binding between the sample drug and a drug chemically labeled with an enzyme, radioisotope, or fluorophore. The sample drug and labeled drug compete for substrate binding sites on drug-specific antibodies.41,42 Similar to competitive binding for enzymatic reactions in the body, the substrate binding site can experience cross-reactivity—causing substances other than the drug in question to bind to the immunoglobulin, leading to a false positive result (TABLE 3).43 Other factors that can alter the results include the cutoff value of the test and the absorption, distribution, metabolism, and excretion of the drug.42 Thus, a confirmatory test of gas chromatography-mass spectrometry is recommended before making decisions based on the results of UDS.43-45
Routine screens for patients on chronic opioid therapy. Routine use of UDS in emergency departments is no longer recommended, based on evidence that the results are unlikely to have a significant effect on patient management.46 For patients on chronic opioid therapy, however, routine screening has proven helpful in detecting prescription opioid abuse, illicit drug use, and diversion. Up to 34% of patients on prescription opioids have been found to be using illicit drugs, as well.42
THE TAKEAWAY: Use UDS as a tool in managing patients on chronic opioid therapy, but before acting on results, assess for factors, such as the use of oral or topical medications and the cutoff value of the test, that may be associated with false positive or false negative results.43-45
8. Thyroid function testing: When should you test?
Thyroid-stimulating hormone (TSH) is the first-line test when investigating presumed hyper- or hypothyroidism.47,48 Third-generation chemiluminometric assays can reliably measure TSH concentrations <0.01 mU/L by using multiple antibodies to produce a sandwich-type effect on the molecule in question.49
TSH levels exhibit diurnal variation, however, and are affected by other medications, including steroids, opiates, and some antihistamines, among others, as well as comorbidities.47,48 Chronic and acute conditions unrelated to thyroid disease can cause transient changes in TSH concentrations, and have the potential to modify the binding capacity of plasma thyroid hormone binding proteins.48 Thus, TSH should be ordered for hospitalized patients only when clinical suspicion of a thyroid problem exists.48 The USPSTF recommends against routine TSH screening for asymptomatic adults.46
How to respond to abnormal results. For patients found to have abnormal TSH levels, free T4 (fT4) is the next test to order.47,49 An fT4 assay is a superior indicator of thyroid status because it is not affected by changes in iodothyronine-binding proteins, which influence total hormone measurements.49 The results will be elevated in hyperthyroidism and reduced in hypothyroidism.47
Triiodothyronine (T3) measures can be useful in diagnosing Graves’ disease, in which T3 toxicosis may be the initial symptom—or an indication of a relapse. Because T3 is often a peripheral product, however, nonthyroid illnesses and medications can cause artifactually abnormal results.49
Other thyroid-specific labs include thyroid ,antibodies such as antithyroid peroxidase, antithyroglobulin, and TSH receptor, both blocking and stimulating.49 Thyroglobulin is a precursor form of thyroid hormone and should be measured when factitious hyperthyroidism is suspected. Management of hyper- and hypothyroidism often is independent of etiology. Retesting TSH to assess treatment response should be postponed until ≥2 months after any change in medication or dosing.50
Thyroid studies can be very difficult to interpret. TSH should be the first test ordered. However, if TSH values do not match the clinical picture, fT4, T3, and other thyroid tests that are less affected by outside factors can be useful in identifying the cause.
THE TAKEAWAY: Routine TSH testing is not indicated for asymptomatic adults. When evaluating thyroid function is clinically indicated, TSH is the initial test of choice.47,48,51
CORRESPONDENCE
Joshua Tessier, DO, Iowa Lutheran Family Medicine Residency, 840 East University Avenue, Des Moines, IA 50316; joshua.tessier@unitypoint.org