Thyroid hormones free hormone measurement

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). 

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. 

In thyrotoxic Graves disease, there is an increase in the overall hormone production rate with a disproportionate increase in T3 relative to T4 (Table 20-1). Saturation of thyroid-binding globulin is increased due to the elevated levels of serum T4 and T3, which is reflected in an elevated T3 resin uptake. As a result, the concentrations of free T4, free T3, and the free T4 and T3 indices are increased to an even greater extent than are the measured serum total T4 and T3 concentrations. The TSH level is undetectable due to negative feedback by elevated levels of thyroid hormone at the pituitary. In... 

Increased TBG leading to increased circulating total thyroid hormone, as measured by PBI, T4 by column, or T4 by radioimmunoassay. Free T3 resin uptake is... 

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. 

No abnormalities were found in Brian s urine and his blood cell count was normal. However, his blood glucose was 8.1 mmol l-1 (normal value 3.5-6.7 mmol l-1) and a glucose tolerance test later indicated impaired glucose tolerance. Tests for plasma insulin and thyroid hormones (T3, T4 and TSH) showed normal levels. Two further tests were then performed. A 24-hour urine sample was collected and Brian s free cortisol excretion was found to be considerably higher than normal. A second test, the dexamethasone suppression test, was also carried out. In this test, the patient is given a dose of dexamethasone at 11 -12 p.m. and plasma cortisol is measured early next morning. 

Serum or plasma is used for the measurement of TSH and the thyroid hormones, with serum free of hemolysis and lipemia preferred. Specimens are stable for 5 days at 2 °C to 8 °C and for at least 1 month when stored frozen. For newborn screening, whole blood is collected by heel puncture 48 to 72 hours after birth. 

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... 

The THBR is derived from a version of the T3 or T4 uptake test. Uptake tests are used to estimate the number of unoccupied (unsaturated) thyroid hormone bindhig sites on serum proteins. This information is important because variations in total thyroid hormone concentrations in blood, as discussed previously, have resulted from changes in binding protein concentrations. Values obtained by uptake methods are expressed as a THBR, which is directly proportional to the free hormone fraction (within limits). Measurement of THBR, in conjunction with a total hormone concentration, is a clinically useful indirect method for calculating the FT4 (or FT3) index. The index approach is particularly useful in patients with nonthyroidal illness in whom FT4 immunoassay methodologies are unreliable. Specifically, TT4 measurement is more diagnostically useful in such patients provided that values are interpreted in accord with the severity of illness in the patient that is indirectly reflected by abnormalities in THBR. 

Measurements of TBG also have been used to derive values for FT4 or FT3 by calculation. Assuming TBG is the major determinant of thyroid hormone binding, serum concentrations of TBG and total T4 (or T3), together with the association constant for the binding of T4 (or T3) to TBG, are used to calculate values of the free hormone. In most cases, these calculated values correlate well with those directly determined. 

Selection and Use of Tests for Measuring Free Thyroid Hormones... 

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. 

In the patient with manifest disease, measurement of the serum T4 concentration, T3 resin uptake (or free T4), and the TSH value will confirm the diagnosis of thyrotoxicosis. If the patient is not pregnant, a 24-hour RAID should be obtained. An increased RAIU documents that the thyroid gland is inappropriately utilizing the iodine to produce more thyroid hormone at a time when the patient is thyrotoxic. 

Little is known about the synthesis of TSH. Direct measurement of serum TSH by radioimmunoassay techniques (R6, Ul) or in vitro or in vivo bioassays (A3, K3) showed that TSH in blood decreased when thyroid hormone was given to hypothyroid persons. Free thyroxine levels were more directly related to the changes in TSH concentration (R6). The half-life of TSH in blood as measured by the use of I-labeled h-TSH is about 30-60 minutes (02, 03). 

Steroid and thyroid hormones bind to specific honnone binding glycoproteins in plasma. It is the unbound or free fraction of the hormone in plasma which is biologically active so measurement of free hormone status or binding protein levels may be important in the diagnosis of patients with thyroid or gonadal disorders. 

Knowledge of thyroid hormone binding in plasma, either by measuring the free hormone concentration or by determining TBG levels, may sometimes be needed in the as.sessment of a patient s thyroid status. 

Free thyroid hormone measurement in the diagnosis of thyroid disease. In... 

Note-. 268 school ohildren aged 8-15 years were screened for iodine deficiency in one region of the Czeoh Republic. Actual serum levels of free daidzein, genistein, thyrotropin (TSH), free thyroid hormones, autoantibodies to thyroid peroxidase (AbTPO) and thyroglobulin (AbTg), and ioduria, along with thyroid volume, were measured. S.E.M. shows standard error of the mean. 

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