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Physicians need quality laboratory support for the accurate diagnosis and cost-effective management of thyroid disorders. Laboratories need to offer methods that are both diagnostically accurate and cost effective. These latter qualities are sometime in conflict. Cost-effectiveness and quality care require that the laboratory serve not only the needs of the majority, but also meet the needs of the minority of patients who have atypical problems that impact the diagnostic accuracy of the tests. Most studies of "cost effectiveness" fail to take into account the human and financial costs resulting from inappropriate management, needless duplication and unnecessary testing of patients with atypical problems that impact the diagnostic accuracy of the tests, and needlessly account for a disproportionately large expenditure of laboratory resources (37). Such problems include binding protein abnormalities that affect the FT4 estimate tests, Tg autoantibodies that interfere with serum Tg measurement, medications or severe NTI that have myriad effects on thyroid tests. It is essential that clinical biochemists develop an active collaboration with physicians using their laboratory services, to select thyroid tests with appropriate characteristics to serve the patient population in question. For instance, the effect of nonthyroidal illness (NTI) on the FT4 method is not important if the laboratory serves exclusively ambulatory patients. In contrast, this is very important for a hospital laboratory that needs to exclude thyroid dysfunction in sick patients. Drugs and other interferences may affect more than 10% of laboratory results in general, and thyroid tests are no exception (19). It follows that discordant thyroid results are often encountered in clinical practice. These discordances need to be interpreted with care using a collaborative approach between clinical biochemists and physicians.
It is recommended that an active laboratory-physician interface be maintained to ensure that quality, cost-effective assays are used in a logical sequence and to assess abnormal thyroid test results and investigate discordances.
The physician depends on the laboratory to provide realistic test data and help to investigate discordant results, whether the tests are performed locally or by a reference laboratory. It is particularly important that the laboratory have readily available data on drug interactions, reference limits, functional sensitivities and detection limits as well as interferences affecting the methods.
The laboratory should avoid frequent or unannounced changes in assay methods and interact closely with physicians before a change in a thyroid test is initiated. The laboratory should be prepared to collaborate with physicians to develop clinical validation data for any new method, as well as data showing the relationship between the old and the proposed new test as well as establish a conversion factor, if necessary.
The diagnostic value and cost-savings of reflex testing strategies (i.e. adding FT3 when FT4 is high, or FT4 when TSH is abnormal) are site-specific (146). Laboratories should only introduce reflex-testing after consultation with the physicians using the laboratory.
It is important that every clinical laboratory develop a relationship with one or more different laboratories that perform thyroid measurements using a different manufacturer's method. Re-measurement of the specimen by an alternative method is the cornerstone of investigating whether a discordance results from an interfering substance in the specimen.
The laboratory should establish and maintain communication with specialized reference laboratories to ensure the availability and high quality of specialized thyroid tests. These specialized tests may include assays for thyroglobulin (Tg) and TSH-receptor antibodies (TRAb). In addition, a reference laboratory offering FT4 measurement by a direct absolute FT4 technique such as equilibrium dialysis should be identified. Direct absolute FT4 testing may be necessary for diagnosing thyroid disease in critical patients with thyroid hormone binding protein disturbances that interfere with the diagnostic accuracy of the FT4 result reported by the clinical laboratory using a FT4 estimate test. In rare cases, it may be necessary to collaborate with a laboratory with the expertise to identify genetic mutations characteristic of thyroid hormone resistance or medullary thyroid disease.
- Have data on the methodologic principles, between-run precision, interferences and any bias relative to other methods readily available for physicians to access, whether the tests are performed locally or sent elsewhere.
Clinical biochemists can reasonably expect that physicians provide relevant clinical information with the submission of the specimen and have a realistic appreciation of the limitations of thyroid laboratory tests. For example, in some conditions the physician should appreciate that immunologic and biologic activity TSH may be dissociated. For example, in patients with central hypothyroidism resulting from pituitary dysfunction the measured immunoreactive TSH has impaired bioactivity. The physician should know that anomalous laboratory results can occur with certain medications and be aware that that the diagnostic accuracy of thyroid tests used in patients with NTI is method dependent.
Without clinical input it is not possible to appreciate the consequences of diagnostic error (37). Many misinterpretations have minor significance, for example, the misclassification of transient changes in serum TSH or FT4 during critical nonthyroidal illness (NTI) as thyroid dysfunction. Other misinterpretations can lead to serious errors such as:
[See Section IIIC for situations where TSH and FT4 are discordant as a result of pathophysiologic conditions or interference with the test result.]
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