Thyroid hormone free

Fig. 1. Mechanisms controlling free thyroid-hormone levels.

H18. Hay, I.D., Bayer, M. F., Kaplan, M. M., Klee, G. G., Larson, P. R., and Spencer, C. A., American Thyroid Association assessment of current free thyroid hormone and thyrotropin measurements and guidelines for future clinical assays. Clin. Cliem. 37,2002-2008 (1991). 

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

Thyroid hormone production is regulated by TSH secreted by the anterior pituitary, which in turn is under negative feedback control by the circulating level of free thyroid hormone and the positive influence of hypothalamic thyrotropin-releasing hormone. Thyroid hormone production is also regulated by extrathyroidal deiodination of T4 to T3, which can be affected by nutrition, nonthyroidal hormones, drugs, and illness. 

TSH-induced hyperthyroidism is diagnosed by evidence of peripheral hypermetabolism, diffuse thyroid gland enlargement, elevated free thyroid hormone levels, and elevated serum immunoreactive TSH concentrations. Because the pituitary gland is extremely sensitive to even minimal elevations of free T4, a normal or elevated TSH level in any thyrotoxic patient indicates inappropriate production of TSH. 

Thyroid function tests - Decreased levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, and there is no... 

Carr D, McLeod DT, Parry G, Thornes HM. Fine adjustment of thyroxine replacement dosage comparison of the thyrotrophin releasing hormone test using a sensitive thyr-otrophin assay with measurement of free thyroid hormones and clinical assessment. Clin Endocrinol (Oxf) 1988 28(3) 325-33. 

The interaction between free thyroid hormones and their binding proteins (TBPs) conforms to a reversible binding equilibrium that is described by the following mass action relationship ... 

Numerous methods have been developed for assessing the concentrations of FT4 and FT3 in serum. These methods include direct assays that currently serve as reference methods and indirect assays that are more widely available for general laboratory use. The following section describes the principles of these methods and offers some guidelines for their use. The theoretical basis, analytical validity, and clinical utility of these methods have been discussed. Special reports from the Nomenclature Committee of the American Thyroid Association, the National Academy of Clinical Biochemistry, and the NCCLS also review some of the issues and concerns regarding free thyroid hormone measurements. 

Historically, direct procedures were too cumbersome, time-consuming, and expensive for use in a routine clinical laboratory. The introduction of very sensitive immunoassays for T4 and T3 combined with improvements in the dialysis or ultrafiltration of undiluted serum has allowed direct measurement of free thyroid hormones. Thus direct equilibrium dialysis and ultrafiltration methods are available for FT4 measurement. 

FT4 assays based on direct equilibrium dialysis or ultrafiltration measure free hormone without the need for total hormone measurements. These methods are unaffected by either variations in serum binding proteins or thyroid hormone autoantibodies. However, IV heparin administration can cause spurious elevations m FT4 determined by these techniques as a consequence of in vitro generation of free fatty acids. Mean values obtained in euthyroid healthy subjects are reported to be slightly higher when using ultrafiltration methods than when using equilibrium dialysis. Analytical performance goals have been recommended for free thyroid hormone assays.When an FT4 assay... 

Indirect Methods for Estimating Free Thyroid Hormones... 

Immunoassays of various designs for estimating free thyroid hormones using antibody extraction techniques have been developed. These assays are subdivided as either sequential two-step assays or simultaneous one-step Canalogue ) assays. Each procedure involves the direct incubation of serum with a specific anti-T4 or anti-T3 antibody, during which thyroid hormones reach a new equilibrium with all of the binders present. A slight decrease in free hormone concentration occurs, but is insignificant if the antibody sequesters less than 5% of the total amount of hormone present in the specimen. Thus the amount of immunoex-tracted T4 or T3 closely approximates the undisturbed free hormone concentration that preexists in serum at equilibrium. 

Prom Hay ID, Bayer MP, Kaplan MK, et al American Thyroid Association Assessment of current free thyroid hormone and thyrotropin measurement and guidelines for future clinical assays. Clin Chem 199i 37 2002 8. 

Rigorous evaluation of free thyroid hormone methods is required before new assays are placed into clinical service. Performance data on analytical accuracy should be obtained not only on serum from patients with thyroid dysfunction but also in serum from patients with binding protein abnor-mahties. Effects of drugs that compete for hormone binding sites on serum proteins should also be evaluated. Moreover, adequate assessment requires an examination of the effects of progressive sample dilution. In theory, the free concentration of T4 and T3 should not decrease with dilution until about 20% of the bound ligand is dissociated. In the case of... 

Ingbar SH, Braverman LE, Dawber NA, Lee GY. A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration. J Clin Invest 1965 44 1679-89. 

Taimela E, Koskinen P, Nuutila P, et al. Free thyroid hormones and a third-generation TSH assay in the detection of hyperthyroidism during long-term thyroxine treatment in thyroid carcinoma patients. Scand J Clin Lab Invest 1995 55 181-186. 

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