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Routine thyroid function tests in infertile women: are they necessary?

To investigate the yield of routine thyroid function testing in infertile women, the records of 444 infertile women were categorized to standard infertility groups. Thyroid function was evaluated by measuring plasma free thyroxine and thyroid-stimulating hormone. All free thyroxine values were in the normal range (0.8 to 1.8 ng/ml), and only three thyroid-stimulating hormone values were higher than the normal range (0.15 to 4.5 mIU/L). The three women had ovulatory dysfunction. Thyroid function testing is more prudent in screening the subset of infertile women with ovulatory dysfunction and not as a routine measure in the infertile population.

Female↗

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↗

Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial.

OBJECTIVES: To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants. DESIGN: Randomised double blind placebo controlled crossover trial. SETTING: Outpatient clinic in a general hospital. PARTICIPANTS: 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls. METHODS: PARTICIPANTS were given thyroxine 100 microgram or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase. MAIN OUTCOME MEASURES: Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. RESULTS: 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the controls. CONCLUSIONS: Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants.

Antibodies↗

[Hereditary thyroxin-binding globulin deficiency--changed thyroid function tests].

BACKGROUND: Variation in concentrations of carrier proteins of hormones may influence the effect of the hormones and may cause confusion in the interpretation of laboratory results. MATERIAL AND METHOD: A Caucasian family with a hereditary thyroxin-binding globulin (TBG) deficiency was investigated. 22 persons in two generations had blood tests for TBG, thyrotropin (TSH), three-iodothyronin (T3), thyroglobulin (TG), thyroxin and for free thyroxin (FT4) by two different commercial tests, Delfia and IMx Abbott (IMx). Relevant health information was collected of all persons. RESULTS: Six males had very low T4 values, non-detectable TBG, increased FT4 values on the Delfia test and within normal range on the IMx test. Six females had lower borderline T4 and TBG. All persons were clinical euthyroid. INTERPRETATION: The condition is considered to represent X-chromosome linked inheritance with hemizygote affected males and heterozygote female carriers with intermediate values for T4 and TBG. Commercial test kits for FT4 may present considerably different results in conditions with TBG deficiency. When a high level of measured FT4 combined with normal TSH is found; TBG deficiency should be considered.

Adult↗

Thyroid function tests in euthyroid dogs treated with L-thyroxine.

The effects of treatment with L-thyroxine (1 mg/m2 of body surface/d, PO, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The TSH response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The TRH response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs. Suppression of the T3 response to TSH was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after stopping treatment, T4 and T3 responses to TSH in 2 dogs were within the hypothyroid range. The T4 response to TRH was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of L-thyroxine to euthyroid dogs.

Animals↗

Admission screening by thyroid function tests in an acute general care teaching hospital.

To determine the incidence of unrecognized thyroid disease among admissions to a large acute care university teaching hospital, 364 samples taken on consecutive admissions were assayed for thyroid-stimulating hormone (TSH) and free thyroxine index (FTI). Patients with abnormal test results were further evaluated by determination of antimicrosomal and antithyroglobulin antibodies, and charts were reviewed for evidence of prior diagnosis of thyroid disease, especially severe illness, drug treatment that might affect thyroid function tests, and prior diagnosis of thyroid disease. Results of subsequent thyroid function tests performed during the patient's hospitalization were correlated with the admission serum assays, and data on subsequent testing during the following 6 months were also obtained. A total of 3.9% of patients had significantly depressed TSH, and 11.1% of values were significantly elevated. A total of 11.3% of patients had significantly low FTI values, and 1% had significantly elevated values. A total of 7.4% appeared to have the euthyroid sick syndrome, 5.8% appeared to have unrecognized or undertreated primary thyroid failure, 6% had apparent subclinical hypothyroidism, 2% were thyrotoxic, and 2.8% (all women) had suppressed TSH levels for inapparent reasons. Limiting testing to patients over 49 years of age, or to women, would have missed many individuals with abnormal test results. Considering widespread availability of tests, relative costs, and value of the information obtained, it is suggested that the FTI determination would provide an appropriate screening test for patients in a population such as this entering a large, acute care general hospital.

Diagnostic Tests, Routine↗

Sick euthyroid syndrome. What to do when thyroid function tests are abnormal in critically ill patients.

Abnormal thyroid hormone concentrations are common in patients with serious nonthyroidal illnesses. Early evidence suggests that thyroid hormone levels may predict the prognosis for some patients. Abnormal thyroid function is usually reversible, but thyroid function tests should be repeated when the nonthyroidal illness is resolved. Whether active intervention using thyroid hormone supplements is beneficial or not remains controversial and requires future large-scale investigation.

Critical Illness↗

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↗

Thyroid function tests in pregnancy.

The recognition of abnormality in thyroid function tests during pregnancy is important for the welfare of the mother as well as fetus. The values of serum tri-iodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH) in nonpregnant women are not applicable during pregnancy and also differ in iodine deficient areas. In the present study, one hundred and twenty-four apparently normal, healthy young primigravidas with no known metabolic disorders and normal carbohydrate gestational intolerance test, consecutively attending the antenatal clinic were included in the study. The serum tri-iodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) in these women were estimated. In the first trimester, the mean T3 values were found to be 1.85 nmol/L, which increased to a mean of 2.47 nmol/L in the second trimester and declined in the third trimester to 1.82 nmo/L. Mean T4 levels were also seen to rise from 164.50 nmol/L in the first trimester to 165.80 nmol/L in the second trimester and then decreased in the third trimester to 159.90 nmol/L. Mean TSH levels were seen to rise progressively through the three trimesters of pregnancy from 1.20 microlU/ ml in the first trimester to 2.12 microlU/ml in the second trimester and further to 3.30 microlU/ml in the third trimester of pregnancy. Three asymptomatic pregnant women (2.5%) were found to have abnormal TSH values with normal T3 and T4 levels and good obstetric outcome. This pilot study also indicates the range to T3 as 1.7 - 4.3 nmol/L in second trimester and 0.4 - 3.9 nmol/L in third trimester, T4 as 92.2 - 252.8 nmol/L in second trimester and 108.2 - 219.0 nmol/ L in third trimester, and TSH as 0.1 - 5.5 microlU/ml in second trimester and 0.5- 7.6 microlU/ml in third trimester of pregnancy.

Adult↗

A multicenter cluster randomized controlled trial of strategies to improve thyroid function testing.

OBJECTIVES: This project aimed to compare the independent and combined effectiveness of two implementation interventions of guidelines for ordering thyroid function tests: a Memorandum Pocket Card (MPC) and a Test Request Form (TRF). RESEARCH DESIGN: Intervention groups were wards. The study used an experimental 2*2 factorial design with matching hospitals according to size and activity and wards according to preintervention appropriateness for test ordering. Four ward groups were established: the dual intervention group, the order form group, the pocket card group and the control group. Physicians in all groups received guidelines and were invited to a local information meeting. MEASURES: The main outcome measure of effectiveness was the Guideline Conformity Rate (GCR). RESULTS: Six hospitals participated in the study (two middle-sized hospitals, two small-sized hospitals and two psychiatric hospitals). A total of 1412 orders for thyroid function tests were collected. GCR was 78% in the dual intervention group, 83% in the order form group, 73% in the pocket card group and 62% in the control group. The interaction between TRF and MPC was not significant (beta = -0.70; P = 0.21). Compared with simple information, TRF was effective in increasing GCR (OR, 2.65; 95% CI, 1.52-4.62), unlike MPC (OR, 1.28; CI, 0.75-2.19). CONCLUSIONS: Using a robust design, our study shows the greater effectiveness of TRF than MPC and their association in implementing thyroid function test guidelines.

Adult↗

Interpretation of thyroid function tests.

The development of radioimmunoassays over the past 20 years has expanded our knowledge of thyroid physiology and improved our management of thyroid disease. The use of these tools in neonatal screening for congenital hypothyroidism alone has reduced the incidence of mental retardation in the industrialized world. Based on an accurate physical examination, the judicious use of immunoassays for thyroxine, triiodothyronine, and thyrotropin and the use of thyroglobulin and thyroid microsomal antibodies will allow the general physician to confidently delineate common thyroid disorders in the great majority of patients. The additional use of an ultrasensitive thyrotropin assay, thyroid scans, and fine-needle aspiration biopsy will complete the accurate diagnosis of the great majority of thyroid diseases. The ultrasensitive thyrotropin assay may become the universal thyroid function test. The major pitfalls in the use of these tests lies in the variable effect chronic illness has on the most frequently used tests: thyroxine and triiodothyronine. Tests for these thyroid hormones, which in the relatively well outpatient are highly accurate, may in the ill, hospitalized patient become very misleading.

Antibodies↗

Evaluation of thyroid stimulating hormone (TSH) alone as a first-line thyroid function test (TFT) in Papua New Guinea.

In the Port Moresby General Hospital, the Chemical Pathology Department assays both thyroid stimulating hormone (TSH) and free thyroxine (FT4) on all requests for a thyroid function test (TFT). The cost of assaying both tests is obviously higher than either test alone. In order to minimize the cost of a TFT we aimed to determine if TSH or FT4 alone as a first-line test would be adequate in assessing the thyroid hormone status of patients. We analyzed TFT records from January 1996 to May 2000 in the Port Moresby General Hospital. A total of 3089 TSH and 2867 FT4 were assayed at an annual reagent cost of Papua New Guinea kina 14,500. When TSH alone is used as a first-line test at the Port Moresby General Hospital, the biochemical status of 95% of patients will be appropriately categorized as euthyroidism, hypothyroidism or hyperthyroidism with only 5% discrepant (ie, normal TSH with abnormal FT4) results. In contrast, using FT4 alone as a first-line test correctly classifies only 84% of TFTs. Euthyroid status is observed in 50% of patients and FT4 assays on these samples will be excluded appropriately if a TSH-only protocol is adopted. Furthermore, we will save a quarter of the yearly cost of TFTs on reagents alone by performing TSH only. We conclude that TSH alone is an adequate first-line thyroid function test in Papua New Guinea and when it is normal no further FT4 test is necessary unless clinically indicated.

Humans↗

Reference intervals of serum thyroid function tests in a previously iodine-deficient area.

AIM: We undertook the present study to establish reference data for serum thyroid function tests in a previously iodine-deficient area. METHODS: Data from 4298 individuals, 20-79 years of age were available for the present analysis. Thyroid function (thyrotropin [TSH], free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (anti-TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: A reference population was selected comprising 1488 persons (825 men) by excluding subjects with known thyroid diseases, and with yet unknown thyroid disorders such as goitre, inhomogeneous thyroid pattern, nodules, hypoechogenicity and anti-TPOAb seropositivity. Reference intervals for serum TSH, FT(3), and FT(4) were 0.25-2.12 mIU/L, 3.8-7.0 pmol/L, and 8.3-18.9 pmol/L, respectively. Reference serum TSH levels were not comparable to the reference values that were recently established for the U.S. population and most reference values slightly differed from the reference values provided by the manufacturers. CONCLUSIONS: The reference ranges of thyroid function tests in this formerly iodine-deficient region are distinct from the reference ranges that were established in areas with iodine sufficiency. Creating a reference population in the present setting should include thyroid ultrasound in order to exclude yet undiagnosed thyroid disorders.

Adult↗