There are many different laboratory techniques to measure estimated free serum T4 and T3. These methods invariably measure a portion of free hormone that is dissociated from the in vivo protein bound moiety. This is of little clinical significance assuming the same proportions are measured for all assays and considered in the calibration of the assay (342). The T3 resin uptake test is an example of one laboratory method used to estimate free T4 in the serum. The T3 resin uptake (T3 RU) determines the fractional binding of radiolabeled T3, which is added to a serum sample in the presence of a resin that competes with TBG for T3 binding. The binding capacity of TBG in the sample is inversely proportional to the amount of labeled T3 bound to the artificial resin. Therefore, a low T3 resin uptake indicates high TBG T3 receptor site availability and implies high circulating TBG levels.
The free T4 index (FTI) is obtained by multiplying the serum T4 concentration by the T3 resin uptake percentage, yielding an indirect estimate of the levels of free T4:
T3 RU% × T4 total = free T4 index.
A high T3 RU percentage indicates reduced TBG receptor site availability and high free T4 index and thus hyperthyroidism, whereas a low T3 resin uptake percentage is a result of increased TBG receptor site binding and thus hypothyroidism. Equilibrium dialysis and ultrafiltration techniques may be used to determine the free T4 directly. Free T4 and T3 may also be determined by radioimmunoassay. Most available laboratory methods used for determining estimations of free T4 are able to correct for moderate variations in serum TBG but are prone to error in the setting of large variations of serum TBG, when endogenous T4 antibodies are present, and in the setting of inherent albumin abnormalities (340).
Because most disorders of hyperthyroidism and hypothyroidism are related to dysfunction of the thyroid gland and TSH levels are sensitive to excessive or deficient levels of circulating thyroid hormone, TSH levels are used to screen for these disorders. Current thyrotropin or TSH sandwich immunoassays are extremely sensitive and capable of differentiating low-normal from pathologic or iatrogenically subnormal values and elevations. TSH measurements provide the best way to screen for thyroid dysfunction and accurately predict thyroid hormone dysfunction in about 80% of cases (343). Reference values for TSH are traditionally based on the central 95% of values for healthy individuals, and some controversy exists regarding the upper limit of normal. Values in the upper limit of normal may predict future thyroid disease (342,344). In a longitudinal study, women with positive thyroid antibodies (TPOAbs or TgAbs), the prevalence of hypothyroidism at follow-up was 12.0% (3.0% to 21.0%; 95% CI) when baseline TSH was 2.5 mU/L or less, 55.2% (37.1%–73.3%) for TSH between 2.5 and 4.0 mU/L, and 85.7% (74.1%–97.3%) for TSH above 4.0 mU/L (345). Physicians ordering thyrotropin
Table 31.10 Thyroid Autoantigens