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Thyroid function tests and diagnostic protocols for investigation of thyroid dysfunction.

Since many tests to investigate thyroid function are currently available, appropriate selection is required to limit the number of assay needed to establish the correct diagnosis of thyroid dysfunction. The limitations inherent in the different tests, and the interferences caused by nonthyroidal factors, especially drugs, must, therefore, be taken into account. Serum total thyroid hormone (TT4 and TT3) determinations are largely affected by changes in the concentrations of thyroid hormone transport proteins (mainly T4-binding globulin). Thus, in many cases, serum TT4 and TT3 measurements do not reliably establish thyroid status. Serum free thyroid hormone (FT4 and FT3) concentrations are independent of transport proteins and more appropriately reflect thyroid status. Serum FT3 measurement is more appropriate for the diagnosis of hyperthyroidism and drug-overdosage in L-T4-treated patients. Conversely, serum FT4 measurement more correctly identifies hypothyroid patients. Serum TSH determination by the currently available sensitive (low detection limit) assays constitutes an indispensable complementary test in both conditions.

Algorithms↗

A simplified strategy for testing thyroid function.

We assessed a new strategy for thyroid-function testing that involves simultaneous measurement of free thyroxin and thyrotropin, both in singletons, with chemiluminescent assays. Using our current strategy of measuring free thyroxin as a first-line test with selected back-up testing, the results show that, of 810 patients without previous thyroid disease, 445 received back-up tests. Of these, 345 were euthyroid, whereas 63 classified as euthyroid and not selected for further testing in fact had abnormal back-up test results. Evidently the simultaneous measurement of free thyroxin and thyrotropin with the "Magic Lite" technology greatly improves diagnostic efficiency compared with this current strategy.

Humans↗

Lithium therapy and thyroid function tests. A prospective study.

Thyroid function tests including thyroxine (T4), T3 test, thyroid-stimulating hormone (TSH), free T4 index and antithyroid antibodies were studied in 51 patients before the start of long-term lithium therapy and after 4 and 12 months on lithium. After 4 months on lithium, changes occurred in all laboratory parameters - T4 and T3 test levels decreased and TSH increased. After 12 months T4 and T3 test increased to pretreatment levels and TSH remained higher than before the start of lithium. During 1 year of lithium treatment only 1 patient developed clinical signs of hypothyroidism and started levo-thyroxine substitution therapy.

Adult↗

Comparison of two doses of aqueous bovine thyrotropin for thyroid function testing in dogs.

Thyroid function was evaluated in 20 healthy dogs by thyrotropin (TSH) response testing. Two dose regimens were used: 5 IU of TSH given IV and 1 IU of TSH given IV. Blood samples were collected prior to and at 4 and 6 hours after TSH administration. Serum was obtained and analyzed for total 3,5,3'-tri-iodothyronine and thyroxine (T4) concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 5 IU of TSH at 4 and 6 hours. The 1-IU dose of TSH failed to induce adequate increase in T4 concentration in 7 dogs at 4 and 6 hours when the criteria for normal response were post-TSH serum concentration T4 greater than or equal to 3.0 micrograms/dl and serum T4 increase by greater than or equal to 100% over baseline serum T4 concentration. One IU of TSH induced increase in serum T4 concentration over baseline; however, the increase was significantly (P less than 0.05) less than that in response to a 5-IU dose at 6 hours after administration of TSH.

Animals↗

Interference in thyroid-function tests in postpartum thyroiditis.

Three women are described from a study of patients with postpartum thyroiditis whose sera gave spuriously increased concentrations of free thyroid hormone because of antibody binding of radiolabeled thyroxin (T4) and triiodothyronine (T3) analogs. All of the women showed increased serum concentrations of thyroid autoantibodies. The antibody binding of radiolabeled analogs and its effect on free T4 and free T3 assays disappeared by 48 weeks postpartum. Postpartum women who develop thyroid autoantibodies have approximately 2% prevalence of increased binding of radiolabeled analogs, which can result in an interference in thyroid hormone assays involving T4 and T3 analogs.

Autoantibodies↗

Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals.

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.

Female↗

Preanalytical considerations in testing thyroid function.

Remarkable technical advances have permitted analytical measurement of thyrotropin (TSH) and estimates of free thyroxine (FT4) with precision, accuracy, and favorable economics. Combined with an increased appreciation of the key insights into the pituitary-thyroid relation, preanalytical considerations infrequently introduce confounding variables. In reviewing thyroid data, preanalytical considerations include physiological and specimen-based issues. Central to the improvement in thyroid assessment is the recognition that physiological individuals maintain their FT4 within narrow limits. When this deviates, there is a logarithmic response of the TSH concentration to the arithmetic shift in FT4. In effect, the TSH deviation magnifies the subtle shift in FT4. Artifact and other nonthyroid-related preanalytical considerations are infrequently the cause of nonconcordance when discrepancy occurs between the reported values for FT4 and TSH. When abnormalities of TSH and FT4 are encountered, the probability strongly favors a disease state rather than a preanalytical variable. Infrequent but real extrathyroidal pathophysiological states are increasingly recognized as a result of the reliable assessment of the pituitary-thyroid relation.

Humans↗

Renal failure and thyroid function tests: the effects of commencing haemodialysis.

Thyroid function tests are often noted to be abnormal in patients with chronic renal failure. We investigated thyroid and pituitary function in six patients with renal failure. In order to study the effects of improvement in the uraemic state on these tests, they were repeated after regular haemodialysis was commenced. Serum thyroxine and free thyroxine levels were at the lower limit of the normal range prior to dialysis and both showed a non-significant increase after regular haemodialysis was started. The TSH response to TRH (TRH test) decreased in five of the six patients after dialysis but this did not achieve statistical significance. The abnormalities in thyroid function tests often observed in clinically euthyroid patients with renal failure do not appear to change significantly after the institution of regular dialysis.

Adolescent↗

Are thyroid function tests too frequently and inappropriately requested?

In spite of data supporting the use of the serum thyrotropin (TSH) concentration as the best test to detect abnormal thyroid function, measurement of circulating thyroid hormones with or without a serum TSH continues to be frequently requested to evaluate thyroid function. We have analyzed how combinations of thyroid function tests were ordered by referring physicians and the results of the tests in order to offer some suggestions as to how to use thyroid function tests in a cost effective manner. During 1995, 19,181 inpatient and outpatient requests (45,865 different tests) for thyroid function tests were received by the laboratory of a 1600 bed University Hospital in Parma, Italy. The following tests were carried out: T4, free T4, T3, free T3 and TSH. Serum TSH values below and above the normal range were considered to reflect abnormal thyroid function i.e. hyperthyroidism, or hypothyroidism including subclinical disease independent of the results of the other tests. Combinations of ordered tests and the percent of the total for each combination were: TSH+T4+T3 (56%), TSH+FT4+FT3 (14%), TSH (12%), TSH+FT4 (9%), TSH+T4 (1%), TSH+T4+T3+FT4+FT3 (5%), others (3%). The T4+T3+TSH panel (10,780 requests) had normal serum TSH values in 80.6% and the FT4+ FT3+TSH panel (2,590 requests) had normal TSH values in 73.2%. Elevated serum TSH concentrations were observed more frequently in hospitalized than in ambulatory patients (9.7% vs 7.4% p<0.001). T3 (elevated serum T3, normal T4 and low TSH concentrations) and T4 (elevated serum T4, normal T3 and low TSH concentrations) toxicosis were observed in 8.1% and 9.4%, respectively, of the requested test (NS). FT3 and FT4 toxicosis, defined as for T3 and T4 toxicosis, were observed in 7.5% and 4.9%, respectively (NS). The low T3 and low FT3 syndrome in hospitalized patients was present in 1.6% and 2.3% of the requests, respectively (NS). The low T4+low T3 and low FT4+low FT3 syndrome was present in only 0.3% and 0.2%, respectively, of the requests. Our study shows that a) in hospitalized patients thyroid function tests were requested in 20% of the patients and only one in 14 of these patients at the highest could have abnormal thyroid function, as indicated by abnormal TSH value b) FT4 (or T4) is as useful as FT3 (or T3) in the diagnosis of hyperthyroidism, c) in hospitalized patients the low T3 syndrome was far less common than that reported in the literature, probably due to the lower severity of illness, d) panels which include T3 and FT3 are not justified, and e) serum TSH alone is the most appropriate initial thyroid function test.

Cost-Benefit Analysis↗

Thyroid function testing based on assay of thyroid-stimulating hormone: assessing an algorithm's reliability.

OBJECTIVE: To assess the ability of an algorithm for thyroid-function testing (based on assay of thyroid-stimulating hormone [TSH]) to discern euthyroidism in patients with and without conditions affecting thyroid function. DESIGN: The Australian Health Insurance Commission (HIC) specifies clinical categories for which Medicare rebate is given for assay of both TSH and free thyroxine (FT4), but otherwise rebates for thyroid function testing are given for TSH assay only. A prospective study was made of paired TSH and FT4 results of 1000 consecutive assays categorised by indication for testing. An FT4 value within the reference range was accepted as indicating euthyroidism; the reliability of an initial TSH measurement as the sole indicator of thyroid disease was assessed against this criterion standard. SETTING: A large suburban teaching hospital. OUTCOME MEASURE: Success or failure of the algorithm, with failure defined as an abnormal FT4 level missed because the TSH level was normal. RESULTS: The algorithm failure rate both overall and in the patients not in the HIC clinical categories was 2.7%, and there was no significant difference in algorithm failure rate in the patients in the various HIC clinical categories. The categories and failure rates were: patients being monitored for thyroid disease, 3.4%; patients with the "sick euthyroid" syndrome, nil; patients with psychosis or dementia, 1.1%; patients taking drugs affecting thyroid function, 2.1%; and patients with pituitary dysfunction, one of six cases. The range of FT4 values in patients in whom the algorithm failed was 6.4-29.5 pmol/L in those without thyroid disease and 3.4-27.4 pmol/L in those with thyroid disease. In patients being monitored for thyroid disease, the proportion of abnormal values of TSH alone was significant (P<0.001). CONCLUSION: We have shown that the HIC's imposition of a TSH-based algorithm by financial fiat is also scientifically acceptable. Use of this algorithm in hospitals (including psychiatric hospitals) will result in substantial savings.

Algorithms↗

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↗

A new strategy for thyroid function testing.

In view of the increasing number of in-vitro tests of thyroid function, rationalization of the biochemical assessment of patients with suspected thyroid disease was attempted. In addition to clinical examination of 285 consecutive new referrals to a thyroid clinic, measurements were made of serum total and free triiodothyronine (T3) and thyroxine (T4) and of thyrotropin (TSH) by radioimmunoassay before and 20 min after thyrotropin-releasing hormone (TRH) and basal TSH by immunoradiometric assay (IRMA). Analysis of these results demonstrated that: (i) a detectable and normal TSH (IRMA) result indicates that the patient is euthyroid and obviates the need for measurement of thyroid hormones and (ii) a raised or undetectable TSH (IRMA) level should be followed by measurement of free T4 (and rarely also free T3) to distinguish between subclinical and overt hypothyroidism and hyperthyroidism. This policy would considerably reduce the number of in-vitro thyroid function tests without resulting in either a delay in diagnosis or a reduction in its accuracy.

Adolescent↗