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The Thyroid Diagnostic cascade has been designed as a diagnostic tool to aid in the initial diagnosis of common adult thyroid disorders. This panel is not intended for use in pediatric patients or in monitoring patients receiving treatment for thyroid disease. This cascade is also not appropriate to use to diagnose primary thyroid neoplasm. The diagnostic cascade begins with sensitive-thyroid–stimulating hormone (TSH), a highly effective screening assay. In patients with an intact pituitary-thyroid axis, TSH provides a physiologic indicator of the functional level of thyroid hormone activity. Increased TSH indicates inadequate thyroid hormone, and suppressed TSH indicates excess thyroid hormone.
TSH: TSH is most often used for the evaluation of the thyroid axis, proper understanding of its utility and limitations is clinically important.
TSH concentrations follow a diurnal rhythm: it typically peaks around midnight and nadir around mid-day. Reference intervals are generally obtained from subjects tested in the daytime, closer to nadir than peak, therefore, when evaluating patient’s serial TSH concentrations, differences in sample collection time should be considered.
TSH Variability: TSH has moderate intra-individual variability and marked inter-individual variability. Since the intra-individual variation is considerably less, when comparing a specific patient’s current TSH level a better approach is to compare with any past level than comparing the patient’s current TSH level to the reference interval. A difference of 0.7 mIU/L or greater is considered significant when evaluating a patient’s serial TSH values.
Method Dependency: TSH methods do not always yield the same result. As much as a 10% difference between results may be generated from different TSH methods. Therefore, the same method should be used when monitoring TSH concentration over time. Similarly TSH reference intervals are also method-dependent and are appropriately applied only to patient results generated from the same method.
Free-T4: Free thyroxine comprises a small fraction of total thyroxine. The free T4 (FT4) is available to the tissues and is, therefore, the metabolically active fraction. Free thyroxine (FT4) are most commonly used in preference to total hormone measurements (TT4 or TT3) to improve the diagnostic accuracy for detecting hypo- and hyperthyroidism in patient populations with the thyroid hormone binding abnormalities.
The majority of these screens will be normal and no further testing will be necessary. However, when the TSH result is abnormal, free T4 (test code T4-FREE) will automatically be performed. Interpretive comments and further test recommendations will be reported based on the TSH and free T4 results. Refer to Thyroid Function Ordering Algorithm.
The TSH results should be interpreted in light of the total clinical presentation of the patient, including: symptoms, clinical history, data from additional tests, and other appropriate information. This assay is not validated for testing neonatal serum TSH levels.
Dopamine and glucocorticoids lower TSH secretion.
Non-thyrometabolic disorders may cause abnormal free T4 levels. Anticonvulsant drug therapy (particularly phenytoin) may result in decreased free T4 levels due to an increased hepatic metabolism. Lithium and iodide preparations lower FT4 levels.
Patients on heparin therapy may have elevated free T4 levels due to release of non-esterified fatty acids, this can alter the relationship between free and bound hormones.