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Abnormal thyroid function tests in devere non-thyroidal illness: diagnostic and pathophysiologic aspects.

In vitro thyroid function tests were studied in twenty-three patients with serious non-thyroidal illness. All had reduced protein binding of serum thyroxine (T4) and serum triiodothyronine (T3) as reflected in increased T4 and T3 uptake tests. The mean T4-binding prealbumin (TBPA) capacity and concentration were about one third the normal levels, whereas the decrease in R4-binding globulin (TBG) was much smaller. Increased serum free fatty acids and reverse T3 were frequently observed, but in vitro displacement of thyroid hormones from their binding sites was achieved only with much high concentrations of these compounds. Other still unrecognized substances significantly inhibiting binding of thyroid hormones might, however, occur in sera of severely ill patients. Evidence in favour of this possibility was the disproportionately high serum T4 by TBG-binding assay relative to T4 by radioimmunoassay. In most of the patients the dual-stage free T4 was elevated, whereas the single-stage free T4 index (CT4I) was within the reference interval. However, neither of these indices reflected the moderately increased dialysable free T4 concentration very accurately. The free T3 index was depressed in most of the patients, whereas the dialysable free T3 concentration was not affected. For practical purposes the combination of normal serum T4 and CT4I in a severely ill patient indicates absence of an associated thyrometabolic disorders.

Adult

[Sex hormone binding globulin (SHBG), a new metabolic in vitro thyroid function test].

SHBG (sex hormone binding globulin) is a carrier protein for the sex hormones testosterone and estradiol with a molecular weight of about 95000 dalton. It can be used as a metabolic test of thyroid function. SHBG was measured by the adsorption method of Mickelson and Petra; the SHBG contained in serum is incubated with 3H-5alpha-dihydrotestosterone and adsorbed to a cellulose filter. Thirty-eight female patients with hyperthyroidism before treatment had markedly elevated levels of SHBG (x +/- SD: 4.85 +/- 2.4 microgram DHT/100 ml) compared with normal controls (1.50 +/- 0.57; p is less than 0.001). A good correlation between the thyroid hormones and SHBG could be domonstrated which was better for T3 than for T4:r =0.76 (p is less than 0.001) for T3 and r= 0.65 (p is less than 0.001) for T4. This agrees with the clinical finding that the circulating T3 level is a better index of the metabolic severity of thyrotoxicosis than T4. After radioiodine treatment SHBG returns to normal values in euthyroid patients (1.38 +/- 0.8; n = 15) and remains elevated in persistent hyperthyroidism (3.99 +/-1,6; n = 67). Even in patients with persistent biochemical hyperthyroidism who are completely euthyroid on clinical examination, SHBG remains high. Despite lack of evidence of clinical hyperthyroidism, this metabolic test demonstrates the biologic significance of merely biochemical hyperthyroidism. Estimation of SHBG as a metabolic thyroid function test in vitro is of special value for the evaluation of patients showing discrepancies between the clinical and biochemical states and for borderline hyperthyroidism.

Carrier Proteins

A critical analysis of some thyroid function tests.

The results of a comparative study of thyroid function tests are reported, the assay for PBI having been used for reference. The merits and sources of error of the Bio-Rad column test, Thyopac-4 test and T3-RIA test are discussed with reference to PBI. The correlation coefficients and the sources of error being taken into consideration, PBI represents a fairly reliable indicator of T4 values and recommends itself on these grounds as a basic routine procedure, the more so as it is simple, cheap and suited for automated analysis. In case of iodine contamination or of the necessity for a selective identification of the T4 factor, the T4 column test is equally reliable. The T3-RIA test will be valuable in special diagnostic problems.

Humans

Thyroid function tests in elderly hyperthyroid patients.

Several tests of thyroid function were performed in 35 hyperthyroid patients over the age of 65 (elderly). The results were compared to those of similar tests in 48 hyperthyroid patients under the age of 65 (young). Total serum thyroxine (T4) was within the normal range in 14 percent of the elderly and 11 percent of the young hyperthyroid patients. The free thyroxine index (FTI) was within the normal range in 11 percent of both groups. The triiodothyronine uptake (T3U) proved to be a poor test in both groups. Although elevation of the triiodothyronine (T3) level allowed a diagnosis of "T3-toxicosis" in 2 elderly and 3 young hyperthyroid patients, the T3 level was normal in 34 percent of the elderly and 13 percent of the young subjects. Correction of the T3 range for age reduced the number of normal T3 values to 12.5 percent in the elderly hyperthyroid patients. The 24-hour uptake of radioactive iodine was normal in 12 percent of the young hyperthyroid patients, 27 percent of the elderly patients with Graves' disease, and 70 percent of the elderly patients with toxic nodular goiter, despite recent readjustment of the normal range for the test. It is concluded that the diagnosis of hyperthyroidism in the elderly may be difficult and that no single test can be relied upon to exclude the diagnosis.

Adult

Simple, rapid thyroid function testing with 99mTc-pertechnetate thyroid uptake ratio and neck/thigh ratio.

To avoid the technical difficulties and errors inherent in the measurement of early thyroid uptake of 99mTcO4-,techniques which are independent of absolute uptake, neck extrathyroidal background and dose standards were evaluated in a series of 108 patients. After intravenous injection of 2 mCi 99mTcO4-, radioactivity was recorded over the neck and thigh. Thyroid uptake ratios were calculated as the ratios of activity over the neck at two times. A neck/thigh ratio was calculated from the recorded activities at 15 min after injection. Examination of these parameters showed that a combination of the 15 min neck/thigh ratio and the 10'/2' thyroid uptake ratio best served to discriminate thyroid function: 92% of hyperthyroid cases were correctly identified by a neck/thigh ratio above 4.7 and 95% of hypothyroid cases were identified by the combination of a neck/thigh ratio below 3 and a 10'/2' thyroid uptake ratio below 1. Correct classification of euthyroidism was 84% but with the exclusion of patients previously treated with 131I, this rose to 91%. The accuracy of the 99mTc procedure is comparable to that of the standard 24 hr 131I uptake run concurrently in this series and duplicates the accuracy of computer assisted determinations of absolute thyroid 99mTcO4- uptakes. The procedure provides a convenient method for the evaluation of thyroid function as an accompaniment to 99mTcO4- thyroid imaging.

Humans

The practical use of thyroid function tests.

The diagnosis of thyroid disorders can usually be established by two tests: the serum T4 and the resin T3 uptake (RT3U). The T4 test measures both free and bound thyroxine; the RT3U reflects the number of binding sites available on thyroid-binding globulin. The values of these two tests can be used to calculate a free thyroxine index (FTI), which gives an approximation of the free T4 in the serum. Measurement of thyroid-stimulating hormone (TSH) is useful for the diagnosis of hypothyroidism, while the thyrotropin-releasing hormone (TRH) test may facilitate diagnosis of hyperthyroidism.

Female

Thyroid function tests in adults with Down's syndrome.

Thyroid status was studied in 24 patients above the age of 40 years with Down's syndrome. Three patients had thyroid function tests indicating hypothyroidism. Eight patients had thyroid autoantibodies in serum and 8 patients had a higher than normal level of thyroid stimulating hormone in serum. None of the patients had figures indicating thyrotoxicosis. None of the patients showed any of the clinical signs usually seen in patients with hypothyroidism. It is concluded that biochemical tests indicating hypothyroidism are much more often seen in patients with Down's syndrome than in normal subjects and that thyroid status should be assessed in old patients with this disease.

Adult

Testing thyroid function.

From the foregoing discussion, it is clear that no single test provides sufficient information to justify its use alone as a single screening test. In vitro tests have now replaced in vivo procedures in the vast majority of patients. Because of the frequency of abnormalities in TBP concentration, the estimation of total T4 should be accompanied by a T3 resin uptake to provide the free thyroxine index or alternatively, a normalized T4 test (Quantisorb or ETR) is preferable. In patients with suspected hyperthyroidism, the initial laboratory evaluation should be an estimate of free T4 and a total serum T3 determination. Whereas the majority of hyperthyroid patients exhibit elevated free T4 levels, a smaller but variable percentage will exhibit only an elevated T3 level. The diagnosis mients where equivocal tests do not provide a diagnosis. In patients with suspected hypothyroidism, estimations of T4 and T3 provide evidence of diminished thyroidal secretion. The diagnosis should be confirmed by demonstration of an elevated TSH level. Normal or low TSH levels point to a diagnosis of pituitary hypothyroidism which can be confirmed by TRH stimulation. The finding of low normal or subnormal T4, normal T3 and elevated TSH levels suggest "compensated hypothyroidism". Estimation of thyroid autoantibodies may confirm the diagnosis of autoimmune thyroiditis. It is emphasized that the approach to testing thyroid function should be an adequate clinical assessment so that selection of the appropriate test(s) currently available leads to a diagnosis of great certainty in most cases.

Autoantibodies

Statistical manipulation for normalization of data: in vitro thyroid function tests.

Interest in chemical and statistical methods chosen to define "normal" populations for the clinical significance of tests has grown recently. Because few clinical values are distributed in gaussian fashion, recommendations for smoothing of data by transforms have been prepared. In this paper we examine mathematical transformations as they are applied to in vitro tests of thyroid function and evaluate the use of multivariate regression analysis. Mathematical transforms used included square root, two parameter log, three parameter log, and inverse hyperbolic sine methods. Multivariate regression analysis was obtained by comparing test data for the T3 uptake, T4, and effective thyroxine ratio with clinical diagnoses as individual and aggregate weighting values for decision. None of the mathematical transforms resulted in complete elimination of diagnostic errors when compared with clinical diagnoses. The effective thyroxine ratio by itself had the highest correlation with patient findings. Additions of other commonly used in vitro function tests added little diagnostic accuracy.

Humans

Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs.

Thyroid function tests were studied in patients undergoing long-term treatment with various anticonvulsant drugs. Previous reports that diphenylhydantoin induces a decrease in the serum concentrations of total and free thyroxine (T4) and triiodothyronine (T3) without a change in the TSH concentration were confirmed. Diphenylhydantoin had no effect on reverse T3. Carbamazepine was also found to decrease serum T4, the free T4 index and T3 but, with the exception of T3, the decrease was smaller than that induced by diphenylhydantoin. Dipropylacetic acid did not influence the serum thyroid hormone concentrations, and neither did primidone. This demonstrates that the interaction between anticonvulsant drugs of different chemical structure and thyroid hormone metabolism is diverse. None of the drugs tested altered serum TSH or the T3 uptake test for the estimation of unsaturated thyroid hormone binding-capacity in serum. These two tests are considered diagnostically more dependable than the measurement of thyroid hormones in serum when diphenylhydantoin and carbamazepine are administered.

Adolescent

The one-step approach to thyroid function tests. The diagnostic thyroxine ratio (DTR)/serum thyroxine (T4) level combination.

A one-step approach to thyroid function tests is reported, using Tetralute kits (Ames). Two parameters are obtained simultaneously--namely, the serum thyroxine (T4) level and the diagnostic thyroxine ratio (DTR), which correlates well with the free thyroxine index (FTI) as determined by two separate tests-the T4 level and the triiodothyronine resin uptake ((T3U)) estimations. Data presented from patients with a variety of thyroid states prove that the DTR, particularly in combination with the T4 level, is adequate for the assessment of thyroid dysfunction in almost all circumstances.

Adolescent

[Correlation studies of some thyroid function tests (author's transl)].

The results of a thyroid test based on ion exchange and column chromatographic separation and of two radiochemical T4 and three T3 tests were carried out with commercially available reagent packs ready for use, and were compared with the PBI values found in the same serum sample in each case. This also tested the analytical precision of each method. A good correlation was found between the PBI and the T4 values, while the accuracy of the T3 tests was unsatisfactory.

Autoanalysis

Thyroid function tests during the early phase of subacute thyroiditis.

Six patients with subacute thyroditis were followed with serial measurements of T4, FT4, TSH and RAI uptake. Five of the six underwent TRH stimulation early in the course of their illness. All six patients had elevated or high normal values for T4 and FT4 at the time of their clinical presentation (mean = 13.8 microgram per 100 ml and 3.9 ng per 100 ml, respectively). RAI uptakes were 1% or less in all six. TRH testing revealed a suppressed TSH response (mean deltaTSH less than0.1 muU/ml) in all five patients tested, suggesting hyperthyroidism. After initial studies were performed, five patients were treated with L-triiodothyronine (L-T3) and one with aspirin. All patients improved over a two to four week period of time, no relapses being noted.

Adult