Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls.

The validity and reliability of serum Tg measurements is central to accurate diagnosis and cost-effective management of patients with differentiated thyroid carcinoma. Serum Tg is one of the most difficult biochemical tests for a laboratory to maintain at a high level of precision and reliability across the long clinical sampling interval typically employed when monitoring this condition. Physicians should be aware that the diagnostic value of serum Tg measurement is method-dependent, and that intermethod differences still approach 30% even after methods have been standardized on the new CBR reference preparation. This dictates that, ideally, serial serum Tg measurements in a patient should always be made in the same laboratory by the same method. Physicians need to consider a number of factors before selecting a laboratory to perform Tg measurements in patients with differentiated thyroid carcinoma. These factors include assay sensitivity, as judged by the discrimination between lower limit of the euthyroid range and the functional sensitivity limit, as well as assay specificity, especially with respect to serum TgAb interference. laboratories should use a sensitive TgAb immunoassay (not hemagglutination) to prescreen sera for TgAb and report the TgAb level if positive. Furthermore, it is the laboratory's responsibility to advise physicians fully about any change in Tg method as well as the direction of TgAb interference expected with that method. When TgAb is present, the serum Tg level should be a measure of the total (free and TgAb-bound) serum Tg level. Typically, IMA methods underestimate the serum total Tg level, especially when serum TSH is suppressed, whereas RIA methods tend to overestimate the serum total Tg level. The interpretation of a serum Tg level in a TgAb-positive patient should be made with caution and with consideration to any changes in TgAb levels. Serial TgAb monitoring of TgAb-positive patients may provide a physician with additional prognostic information on outcome. Precise, reproducible serial serum Tg measurements are critical, especially when patients are judged to have a high risk for recurrence, have tumors that are inefficient serum Tg secretors (as judged from the relationship between the preoperative serum Tg value and tumor mass or the serum Tg response to endogenous TSH stimulation), or have very high serum Tg values requiring dilution. In such patients, the banking of left-over sera (frozen) for concurrent intra-assay remeasurement with a more recent specimen significantly increases the clinical value of the test and facilitates earlier detection of recurrence or progression (see Fig. 2). Differentiated thyroid carcinoma is frequently diagnosed in young patients with decades of life expectancy. After their initial surgical treatment, these patients need life-long monitoring, because late recurrences and death from the disease can occur. The use of high-quality serum Tg measurements can significantly improve the cost-effective management of this disease by identifying low-risk patients in whom periodic radioiodine scans or therapy may be deferred in favor of serial serum Tg monitoring (on L-T4 suppression therapy). With this approach, expensive imaging procedures can be targeted to the minority of patients who are at high risk for recurrence.