Horm Metab Res. 1992;. Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;. Brent GA, Hershman JM, Braunstein GD. Patients with severe nonthyroidal illness and serum thyrotropin concentrations in the hypothyroid range.It is performed by mixing a comparatively low affinity solid phase T3 resin binder with an aliquot;of the patient's serum to which is added a trace amount of 125I-labeled T3. The 125I-T3 partitions between solid-phase resin binder and serum binding sites, and at the end of the incubation the supernatant serum is removed.
Intraassay coefficient of variation is on the order of 5; interassay variation is approximately 7. Irrespective of how precise the quantification of T4 is, there is appreciable overlap of the values between normal subjects and hypothyroid or hyperthyroid patients.1990;. Spencer CA, LoPresti JS, Patel A, et al. Applications of a new chemiluminometric TSH assay to subnormal assessment. J Clin Endocrinol Metab. 1990;. Kaptein EM. Clinical application of free thyroxine determinations.
Free Thyroxine Index Inasmuch as changes in the T3RU caused by binding abnormalities are discordant with changes in T4, the T3RU has been used to correct the total T4. This corrected T4, the free T4 index (FT4I is generally calculated as follows: The resultant number is expressed without units and is illustrated by the following.Definition Thyroid function tests are designed to distinguish hyperthyroidism and hypothyroidism from the euthyroid state. To accomplish this task, direct measurements of the serum concentration of the two thyroid hormonestriiodothyronine (T3) and tetraiodothyronine (T4)more commonly known as thyroxine, are extensively employed.
No single estimation of T4, corrected or otherwise, can reliably identify the status of thyroid function in all patients. Free Thyroxine A more accurate method of assessing thyroid function is to measure the concentration of free T4 using an equilibrium dialysis technique.Estimates of fractional thyroid iodide uptake have been employed for decades using 131I as a marker. Because of the relative low cost and accuracy of the direct measurements of serum hormone concentration, the 131I uptake has fallen into disuse.
In: Klee. GG, ed. Clinics in Laboratory Medicine: Pathophysiology of Thyroid Disease. Philadelphia, PA: W.B. Saunders Company;. Ross DS. Subclinical hyperthyroidism: possible danger for overzealous thyroxine replacement therapy. Mayo Clin Proc.In this section, the generally available tests of thyroid function and their limitations are described. Their appropriate use and interpretation should allow an accurate assessment of thyroid status in almost all cases.
Clin Chem. 1996;. Ridgway EC. Modern concepts of primary thyroid gland failure. Clin Chem. 1996;. Nicoloff JT, Spencer CA. The use and misuse of the sensitive thyrotropin assays. J Clin Endocrinol Metab.The T3 resin uptake (T3RU) is used as an indirect measure of serum thyroid hormone binding capacity, and the Free T4 index (FT4I derived from the T4 and T3RU, corrects estimates of T4 for serum binding abnormalities.
Free T4: total serum free (more.) Triiodothyronine Resin Uptake. Patients with high or low T4 values often have increased or decreased concentrations of TBG rather than abnormal rates of T4 production.Conversely, a patient with reduced concentration of TBG and a corresponding low concentration of total T4 would have a high T3RU. These changes are outlined in. Table 142.1 T3 Resin Uptakes and T4 Concentrations Expected with Various Conditions.
The most useful of these is the TSH releasing hormone (TRH) challenge wherein TSH is measured before and after TRH infusion. The characteristic response patterns in hyperthyroidism and in various types of hypothyroidism are diagnostic when taken in conjunction with the rest of the clinical picture.Iodide has essentially no effect on the T4 antibody interaction. Two infrequently encountered compounds that displace circulating T4 from TBG binding sites, diphenylhydantoin and salicylic acid, also have no effect on the T4 antibody interaction.
For clinical purposes, the T4 antibodies have adequate specificity. The variable number of high-affinity TBG binding sites in serum would tend to abort the precisely controlled interaction of a limited quantity of antibody binding sites with unknown amounts of T4.Conversely, in hypothyroidism less label is bound to the resin binder because of the reduced amount of endogenous T4 competing for a normal complement of TBG sites. With a primary increase in TBG concentration the RU is also reduced, but now because of an excess of TBG rather than a reduction of T4.
The 125I-T3 activity remaining on the resin binder divided by total 125I-T3 added and then multiplied by 100 defines percentage RU. Normal values vary between 25 and 50 and are a function of the type of solid phase binder used and the conditions employed for incubation.Am J Med. 1986;. Hamblin PS, Dyer SA, Mohr VS, et al. Relationship between thyrotropin and thyroxine changes during recovery from severe hypothyroxinemia of critical illness. J Clin Endocrinol Metab. 1986;.
The dextro isomer of T4 generally binds as well to antibody, as does the naturally occurring levo isomer, but the dextro isomer is not naturally present in biological fluids in measurable quantities.This requires a grasp of thyroid physiology, a knowledge of the limitations of the tests in question, and a thorough understanding of the patient. Given these prerequisites, the outcome will often be helpful, but a number of common clinical circumstances cause changes in the tests that can mislead the unknowing.
Figure 142.1 Thyroid function studies in normal subjects and in hypothyroid and hyperthyroid patients. Cross-hatched areas represent the respective normal ranges. T4: total serum thyroxine. T3RU: T3 resin uptake. FT4I: free thyroxine index.Nelson JC, Clark SJ, Borut DL, et al. Age related changes in serum free thyroxine during childhood and adolescence. J Pediatr. 1993;. Fisher DA. Physiological variations in thyroid hormones; physiological and pathophysiological considerations.
Clin Chem. 1996;. Faglia G, Beck-Peccoz P, Piscitelli G, et al. Inappropriate secretion of thyrotropin by the pituitary. Horm Res. 1987;. Ohzeki T, Hanaki K, Motozumi H, et al. Refractoriness at peripheral and pituitary receptors in general and pituitary types of thyroid hormone resistance.Similar constructs for low binding states versus hypothyroidism can be developed from. In, comparison of the total T4 with the FT4I shows that the latter test discriminates better between normals and abnormals, but there is still overlap between subsets of patients.