Free Thyroid Hormone Measurements Research Articles

Variations in thyroid hormone transport proteins and their clinical implications.

Variations in major thyroid hormone transport proteins may be inherited or acquired and may be associated with changes in serum concentration of the proteins or their affinity for thyroid hormones. These variations most frequently involve thyroxine-binding globulin (TBG), but changes in transthyretin and albumin are also observed. The consequent alteration of thyroid hormone-binding capacity in serum is associated with variations in total thyroid hormone concentration. Increased serum total thyroid hormone levels are found in subjects with TBG excess, familial dysalbuminemic hyperthyroxinemia, and transthyretin-associated hyperthyroxinemia. Conversely, diminished serum thyroid hormone values are observed in subjects with TBG deficiency, and decreased concentration or affinity of transthyretin and albumin is not associated with variations in serum concentrations of thyroid hormones. The transport protein-associated variations in serum total thyroid hormone concentrations do not reflect a change in thyroid status. Euthyroidism can be easily established in subjects with transport protein abnormalities by the normal free thyroid hormone and TSH concentrations. It is, however, crucial to select methods for free thyroid hormone measurement that are not affected by abnormalities of transport proteins. Some assays, such as the analog method, often provide artifactual and misleading results, which may lead to inappropriate and even detrimental treatments. The evolutionary advantage of TBG (and albumin) in terms of thyroid homeostasis still remains to be elucidated.

American Thyroid Association assessment of current free thyroid hormone and thyrotropin measurements and guidelines for future clinical assays. The Committee on Nomenclature of the American Thyroid Association

American Thyroid Association assessment of current free thyroid hormone and thyrotropin measurements and guidelines for future clinical assays. The Committee on Nomenclature of the American Thyroid Association

Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns

Evaluation of thyroid status by measurement of free thyroid hormone concentrations seems particularly helpful in conditions with altered serum binding proteins. In pregnancy, a condition of increased thyroxine binding globulin, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations have been reported to be normal, increased or decreased. In the present study we have measured serum total and free thyroid hormone concentrations in pregnant women, their newborns and nonpregnant women. Serum FT4 and FT3 concentrations have been measured with 10 different commercially available kits and the results obtained have been compared. Serum total thyroid hormone concentrations in pregnant women were significantly higher than in their newborns and in nonpregnant women. Maternal serum FT4 concentrations measured with the different kits were always significantly lower than values in nonpregnant women. Furthermore, with one kit, the mean maternal serum FT4 concentration was below the normal range and with many kits, a large number of maternal serum samples had serum FT4 concentrations below the normal range. With all kits, except two, neonatal serum FT4 concentrations were higher than values in their respective mothers and, in general, lower than values in nonpregnant women. Serum FT3 concentrations in nonpregnant women were in the normal range, except with one kit, in which the mean serum FT3 concentration was below the normal range. Serum FT3 concentrations in newborns resulted markedly lower than in parturient and in non pregnant women. With almost all kits, serum FT3 values were below the normal range in many maternal samples. With one kit, maternal serum FT3 concentrations resulted higher than in nonpregnant women, whereas with the other kits serum FT3 concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid Function Tests in Elderly Patients with and without an Acute Illness

Thyroid function was assessed by measurement of free thyroid hormones and thyrotrophin (TSH) in 78 acutely ill elderly patients and in a control group without acute illness. Abnormal results with any test were more frequently found in the acutely ill group than in controls. In particular, abnormal TSH values were found in 40% of the acutely ill group and in only 8% of controls (p less than 0.001). Seven acutely ill subjects had very low TSH levels (less than 0.04 mU/l) and a blunted response to thyroid-releasing hormone (TRH). With few exceptions these abnormalities could not be attributed to thyroid disease. This suggests that pituitary TSH secretion can be impaired in euthyroid sick old people. High sensitivity TSH assays may therefore be inappropriate as first-line tests of thyroid function, at least in this select group.

Use of Sensitive Immunoradiometric Assay for Thyrotropin in Clinical Practice

Although measurement of thyrotropin (thyroid-stimulating hormone; TSH) by radioimmunoassay was a major advance in the laboratory diagnosis of thyroid failure--replacing the time-consuming TSH stimulation test--it was not sufficiently sensitive to discriminate reliably between euthyroid and hyperthyroid patients. Measurement of the TSH response to thyrotropin releasing hormone (TRH) served this purpose, however. The recent development of TSH assays that are severalfold more sensitive and more specific than conventional radioimmunoassays has allowed distinction of euthyroid from hyperthyroid patients and eliminated the need for the TRH test. Although undetectable levels of TSH, compatible with hyperthyroidism, are occasionally noted in euthyroid patients with severe nonthyroidal illness and during the first trimester of pregnancy, false-positive results are less often recorded for TSH than for free or total thyroid hormone measurements. Measurement of TSH by sensitive immunoradiometric assay is currently the most useful first-line test of thyroid function in patients with suspected thyroid disease and, in addition, has a valuable role in monitoring the dose of thyroxine replacement therapy.

Serum free thyroid hormones in different degrees of hypothyroidism and in euthyroid autoimmune thyroiditis.

Serum total and free T4 and T3, thyroxine-binding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 micrograms, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of free thyroid hormones in patients on long-term phenytoin therapy.

Total thyroxine and triiodothyronine levels are often reduced in long-term phenytoin therapy, a finding at variance with the euthyroid clinical state of these subjects. We have measured free (biologically active) thyroid hormone levels in 31 patients on phenytoin therapy and have found a significant reduction in measurements of both free thyroxine and free triiodothyronine. In contrast, addition of phenytoin to normal serum in vitro resulted in an increase in free thyroxine and free triiodothyronine concentrations. The findings in vitro are consistent with displacement of thyroid hormones from thyroxine binding globulin while the reduced free hormone levels in vivo confirm that the effects of phenytoin are not confined to binding inhibition and suggest that phenytoin has induced a change in the cellular metabolism of thyroid hormones.

Clinical implications of the measurement of free thyroid hormones in thyroid disease.

SUMMARYWe determined the dialysable fractions of T3 (DFT3) and T4 (DFT4) to study the behaviour of free thyroid hormones in different states of thyroid function.The relationship between DFT4/TBG and DFT3/TBG in forty‐nine individuals, (nine hyperthyroid, ten euthyroid, ten hypothyroid patients, ten pregnant women and ten subjects taking oral contraceptives) was best described in both instances by two regression curves. The first regression showed that both DFT4 and DFT3 were inversely correlated with TBG. The second regression described the nine most biochemically toxic patients. They were statistically independent of the first, and being almost perpendicularly disposed to the TBG axis were interpreted as saturation curves. Analysis of the discriminant value of free thyroid hormone levels (AFT3, AFT4) derived from DFT3 and DFT4 showed that free thyroid hormone measurements were in no way superior to total thyroid hormone measurement in the biochemical diagnosis of hyper‐ and hypothyroidism. Furthermore, there were no signficant differences in DFT3, DFT4, AFT3 and AFT4 between patients and controls in subjects whose only abnormality was a decreased (n=18) or exaggerated (n=9) TSH response in the TRH test. Finally, mean total T3 and AFT3 were both significantly higher than controls in patients with hot nodules who were hyperthyroid (n=9) but only AFT3 was higher in corresponding patients (n=9) who were euthyroid.

Measurement of free thyroid hormones in serum by dialysis and gas chromatography.

We describe a simultaneous, absolute analysis for free (dialyzable) triiodothyronine and thyroxine in serum by the sequence: dialysis, internal standard addition to the dialysate, cation-exchange chromatography, derivatization, and gas chromatography with electron capture detection. The detection limit is 0.2 pg and the precision (repeatability) in the range of 4 to 20 ng/liter is 1.6%. Mean values for free T3 and T4 in 29 euthryoid sera were 4.2 and 18.9 ng/liter, respectively, in close agreement with accepted values. Correlation coefficients for the two compounds were 0.99 and 0.97, respectively, when this procedure was compared with a method involving tracer dialysis and radioimmunoassay. A chromatographic peak was seen for free 3,3',5'-triiodothyronine in the analyses of two of eight hyperthyroid sera, and, with a larger sample volume, from a euthyroid serum. The new method is a potential reference and research procedure for analysis of free iodothyronines.