Update on thyroid function testing.
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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.
We compared the utility of a sensitive immunoradiometric assay for serum thyrotropin as a "first-line" thyroid-function test with a strategy based on first measuring total thyroxin in serum. The immunoradiometric assay appears to distinguish primary hypothyroidism and hyperthyroidism from euthyroidism in "new" patients. The role of this test in monitoring antithyroid treatment or thyroxin-replacement therapy is not yet established, there being particular difficulty in interpreting low thyrotropin concentrations in such patients. Nevertheless, because a normal thyrotropin concentration in most, if not all, situations signifies the euthyroid state, thyrotropin determination by immunoradiometric assay merits consideration as an initial test by laboratories performing thyroid-function tests.
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The first major variation from the normal human levels of thyroxine-binding globulin (TBG) in a racial group is reported in full-blood Aborigines of Western Australia. This finding has not only biochemical and anthropological interest, but also medical significance in that many common laboratory tests of thyroid function in this group are very liable to misinterpretation because of low TBG levels. In Aborigines in the Halls Creek area of Western Australia, 40% have TBG levels below the lower reference limit for Caucasians, and 18% have levels between half and one-third of the lower limit. Such subjects have low thyroxine levels by Caucasian standards, and frequently the results of triiodothyronine uptake (T3U) tests lend support to the false suggestion of hypothyroidism. Caucasian reference ranges are not valid in this large proportion of the Aboriginal population. It is not yet clear whether the low TBG levels are a normal feature in this racial population, or whether there is some other cause. The subjects of the study were not acutely ill and Aborigines with low TBG are well distributed throughout the State.
We studied the ability of thyroid function tests to predict hospital survival in 116 critically ill patients and compared the results with independent predictions of survival made by critical care physicians. Eleven patients (9.5%) had clinically unsuspected hypothyroidism and were less likely to survive (p = 0.03). In patients critically ill with nonthyroidal disease, low T3, low FT3I, low T4, low FT4I, high TSH, and high T3U levels each showed significant correlation with nonsurvival (all p less than 0.02). Of these, however, only low T3 (p less than 0.001) and high TSH (p = 0.016) showed significant independent prediction of nonsurvival, and only low T3 (p = 0.011) added any significant independent prediction of nonsurvival beyond that made clinically by the group of critical care physicians.
We report intra-individual and seasonal variations of thyroid function tests in healthy subjects. Blood samples were obtained from thirteen healthy males and seven healthy females every two weeks over a period of one year, and totally 25 samplings of each were made. Serum thyrotropin (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) were measured after the completion of the sampling. The 25 samples from each subject were always assayed with the same assay run. Variations of FT4 and FT3 in each subject were narrow and approximately one-third of normal reference ranges. The magnitude of individual variation of TSH values was proportional to the average of TSH in each individual. Serum TSH and FT3 values during winter were significantly higher than those during summer, but such change was not observed on serum FT4.
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OBJECTIVE: To investigate the relationship between results of maternal thyroid function tests and endothelin levels in preeclamptic or eclamptic women. METHODS: Thyroid hormones, TSH, and endothelin were measured in plasma or serum from 37 proteinuric, preeclamptic or eclamptic women and 20 normotensive, nonlaboring, pregnant women. Subjects were subdivided into four groups according to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and birth weights of infants with respect to gestational age. RESULTS: A significant decrease in concentrations of total thyroxine (T4) (13.76+/-1.84 microg/dL versus 10.00+/-1.48 microg/dL, P < .05), total triiodothyronine (T3) (180.58+/-30.84 ng/dL versus 141.16+/-27.31 ng/dL, P < .01), free T4 (1.45+/-0.27 ng/dL versus 1.10+/-0.21 ng/dL, P < .01) and free T3 (3.32+/-0.56 pg/mL versus 2.41+/-0.60 pg/mL, P < .01) and a significant increase in TSH (1.55+/-0.89 microIU/mL versus 2.96 +/-1.07 microIU/mL, P < .05) and endothelin (2.31+/-0.61 pg/mL versus 6.11+/-1.41 pg/mL, P < .001) levels were observed in the preeclamptic-eclamptic group compared with the normotensive group. Also, women without HELLP syndrome and without small-for-gestational-age infants had elevated levels of thyroid hormones and decreased levels of TSH and endothelin compared with other subgroups, but stastical significance was reached only in total T4 (P < .05), TSH (P < .05), and endothelin (P < .001). Birth weights of infants born to preeclamptic or eclamptic women correlated positively with total T4 (P < .01) and total T3 (P < .01) and negatively with TSH (P < .01) levels. A more significant negative correlation was found in preeclamptic-eclamptics (P < .001) between birth weight and endothelin levels than in control subjects (P < .05). Endothelin levels in preeclamptic or eclamptic women correlated negatively with total T4 (P < .01), total T3 (P < .05), free T4 (P < .05), and free T3 (P < .05) and positively with TSH levels (P < .01) compared with control subjects. CONCLUSION: Moderate decreases in thyroid hormones with concomitant increases in TSH levels in maternal serum correlated with severity of preeclampsia or eclampsia and high levels of endothelin. Changes in results of thyroid function tests induced by preeclampsia or eclampsia might be consequences of the dysfunction in the hypothalamic-pituitary-thyroid axis, secondary to the disease itself.
Thyroid function was evaluated in patients affected by Fisher-Evans syndrome (FES) and compared to that of patients affected only by autoimmune hemolytic anemia (AIHA) and to that of patients affected only by idiopathic thrombocytopenic purpura (ITP). The study population consisted of 20 patients with FES, 44 with AIHA and 20 with ITP. All patients were examined for thyroid function abnormalities and thyroid autoantibodies. Abnormal thyroid function test results were observed in 40, 25 and 10% of the patients, respectively. The prevalence of antithyroid antibodies (ATA) in FES was 25%; this is higher than the sum of the prevalences of ATA in patients affected only by AIHA (11.4%) or only by ITP (none). Subclinical primary hypothyroidism and hyperthyroxinemia with or without hypertriiodothyroninemia, with TSH serum levels below normal, were present in 20% and 10% of patients affected by FES, respectively. Of the former, 75% were positive for ATA. These results: i) confirm the high prevalence of abnormal thyroid test results in patients affected by AIHA, ITP and FES; ii) demonstrate the higher prevalence of autoimmune hypothyroidism in FES; iii) lead to the possibility of including FES as one of the multiple autoimmune syndromes.
We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid function test in prostate cancer patients. Serum levels of tri-iodothyronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined in a cross-sectional study that included 279 patients diagnosed with prostate cancer. A subset of 96 patients free of prostate-specific antigen relapse after radical prostatectomy became a control group and 183 patients under continuous ADT formed the study group. Sixty-four patients out of the study group were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119 with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3-218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively, p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58), respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80-1.90), respectively, p=0.018. No statistically significant differences between the T3, T4, TSH and FT4 serum levels were detected according to the modality of ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%); however, all cases had a normal FT4 serum level. This mild hypothyroidism was detected in two of the 96 patients of the control group (2.1%) and in four of the 183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function test. A statistically significant increase in TSH serum level and a decrease in FT4 serum level were detected in patients under ADT. However, only a mild hypothyroidism was detected in about 2% of the patients with prostate cancer, independently of ADT.
OBJECTIVES: Changes in thyroid hormone levels in non-alcoholic cirrhotic patients with hepatic encephalopathy were investigated in order to determine whether thyroid function tests could be a useful prognostic indicator for acute outcome. METHODS: Patients with hepatic encephalopathy due to non-alcoholic cirrhosis were studied at Erciyes University Hospital, Kayseri, Turkey, between August 1990 and October 1991. Nine of them were males and eight females, with ages ranging between 22 and 69 years. Eleven cirrhotic patients who had no encephalopathy of any degree comprised the control group. Patients with hepatic encephalopathy were divided into two groups: survivors and non-survivors. The levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), free T3 (FT3) and free T4 (FT4) were obtained in both patients with and without encephalopathy. Alterations of thyroid function tests and their relation to acute outcome were evaluated. RESULTS: Serum T3 and FT3 levels were significantly lower in the patients who died of encephalopathy compared with controls (p < 0.05). Serum FT3 and FT4 were also lower in the survivors compared with those of the cirrhotic controls (p < 0.05). Albumin was found to be the unique and most important prognostic factor with a difference between survivors and cirrhotic controls (p < 0.05). CONCLUSIONS: These data suggest that patients with liver disease due to non-alcoholic cirrhosis are under great risk for hepatic encephalopathy when they have low FT3 levels. The decrease of serum T3 and albumin levels could be considered as indicators of poor prognosis for acute outcome.
Determination of thyrotropin (TSH) by sensitive immunometric assays is currently judged as the most sensitive and also most cost-effective first-line approach to thyroid function testing. Further improvement of assay sensitivity has led to the description of third generation TSH assays with a functional sensitivity in the range of 0.01 to 0.02 mU/l. In the present study, we analyzed interassay precision profiles of a commercially available third generation assay (ACS:180 TSH-3) and documented the critical role of the time span used for the assessment of a method's functional sensitivity. By using a standardized approach with five serum pools measured in 30 different runs across a 6-week period, functional sensitivity was calculated as 0.015 mU/l. The TSH concentrations measured by two different third generation assays (ACS: 180 TSH-3 and Elecsys TSH) in samples from healthy blood donors were highly correlated (r = 0.76, n = 252). In some samples, however, discordant results were obtained. Euthyroid reference intervals were determined as 0.30-3.68 mU/l for the ACS:180 TSH-3 assay and as 0.36-3.64 mU/l for the Elecsys TSH assay. Reevaluation of reference intervals including only TPOAb or TgAb negative samples resulted in almost the same reference ranges. Measuring TSH concentrations in various patient populations, third generation assay turned out to be advantageous in the following clinical situations. (a) In patients with mildly suppressed but well detectable TSH concentrations due to functional thyroid autonomy (0.03-0.3 mU/l), overt hyperthyroidism can be excluded by third generation TSH measurement alone without the need of additional thyroid hormone measurements; (b) in patients receiving long term suppressive T4 treatment after thyroidectomy for differentiated thyroid cancer, measurement of basal TSH by third generation assays allow accurate monitoring of hormone therapy without the need for TRH testing; (c) in most patients with severe nonthyroidal illnesses and decreased TSH levels, TSH concentrations measured by third generation assays are only moderately suppressed and can be clearly discriminated from undetectable levels in overt hyperthyroidism. In conclusion, the use of third generation TSH assays is recommended in specialized clinical laboratories frequently analyzing samples taken in one of those clinical situations.
Serious nonthyroid illness and caloric deprivation, which so often accompany systemic illness, have diverse and still incompletely understood effects on thyroid hormone economy. We have discussed the pathophysiologic basis for the most common pattern of alterations in routine thyroid function tests: a decreased serum T3 concentration; normal or, in critically ill patients, a low total serum T4 level; and a normal free T4 concentration. Another, less frequent pattern (high total and free T4 with a normal serum T3) can be encountered transiently in the acutely ill medical or psychiatric patient. With the recent advent of sensitive assays for TSH and better methods for serum free T4, it is now possible to define more quickly and accurately the thyroid-metabolic status of most of these sick patients; the vast majority are euthyroid. Certain drugs confound the picture. The most important of these include dopamine and high-dose glucocorticoids, both of which suppress TSH secretion from the pituitary and may actually cause a state of central hypothyroidism. Other drugs have multiple effects on thyroid hormone indices (e.g., amiodarone). Knowledge of all of the ways in which systemic illness, starvation, and certain drugs may influence thyroid function tests is crucial in assessing the thyroid status of patients with serious nonthyroid disease.
Measurement of thyrotropin concentration alone as a first-line thyroid-function test fails to indicate hypopituitarism in a number of patients. Using a combination of thyrotropin and thyroxine assays, we analysed 56,000 tests for a population of 471,000 over 12 months. 15 patients with clinically unsuspected hypopituitarism were detected, indicating that the occurrence of hypopituitarism might be underestimated.
The effect of phenobarbital treatment in late pregnancy on thyroid function tests was investigated in 16 women. Ten women in late pregnancy served as controls. Phenobarbital treatment for two weeks was associated with a significant decrease in serum thyroxine (T4) level and in the free thyroxine index (T3U x T4) of 18% and 16%, respectively. These changes were associated with a significant increase in serum thyrotropin concentration of 15%. gamma-Glutamyl transpeptidase activity increased, and serum bilirubin concentration decreased during phenobarbital treatment. The changes in the thyroid function test might reflect the effect of phenobarbital on thyroid hormone metabolism. The changes may have diagnostic importance in borderline cases of thyroid disease.
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