Assessment of treatment outcomes in hyperthyroid cats treated with an orally administered fixed dose of radioiodine.

OBJECTIVES: The aims of this study were to describe the treatment outcomes following oral administration of a fixed dose (138 MBq; 3.7 mCi) of radioiodine in hyperthyroid cats and to examine the correlation between total thyroxine (TT4) concentrations before and after treatment. METHODS: This was a retrospective cohort study that documented the TT4 concentration and clinicopathological parameters at the time of diagnosis and after treatment. Logistic regression was used to assess the relationship between TT4 concentrations before and after treatment. The difference in pre- and post-treatment variables between cats that had TT4 concentrations below or within the reference interval (RI) was compared by the Mann-Whitney U-test. RESULTS: Of 161 cats, 133 (82.6%) cats had TT4 concentrations within the RI, four (2.5%) cats had TT4 concentrations above the RI and 24 (14.9%) cats had TT4 concentrations below the RI after treatment. The severity of hyperthyroidism at diagnosis, as measured by the percentage of TT4 elevation above the upper limit of the RI, had no impact on the odds of cats having low TT4 concentrations after treatment (odds ratio 1.00; 95% confidence interval 0.96-1.05; P = 0.828). CONCLUSIONS AND RELEVANCE: When using an orally administered fixed dose of radioiodine for the treatment of feline hyperthyroidism, TT4 concentrations at diagnosis cannot be used to predict TT4 concentrations after treatment. The proportion of cats with TT4 concentrations below the lower limit of the RI after treatment was 14.9%. Further work is required to optimise oral radioiodine dosing to achieve maximal euthyroid outcomes.

Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?

A clinical study was initiated in response to patients' complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100µg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life.

Thyroxine and triiodothyronine content in commercially available thyroid health supplements.

BACKGROUND: As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support." METHODS: Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards. RESULTS: The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3-25.4 µg/tablet) and 5 of 10 contained T4 (5.77-22.9 µg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 µg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 µg/day. CONCLUSIONS: The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.

[Assessment of thyroid hormones and androgens in amniotic fluid: clinical interest]. / Dosage des hormones thyroïdiennes et surrénaliennes dans le liquide amniotique: aide au diagnostic.

Ultrasound scanning is able to detect foetal goiter due either to an hypothyroidy either to an hyperthyroidy, or clitoris hypertrophia resulting from adrenal hyperplasia in female, during the second half of pregnancy. The diagnosis of these rare diseases is of interest because the treatment can be started during pregnancy. An amniotic fluid punction can be discussed and its biochemical analysis may be of interest even though very few commercial assays have been tested on amniotic fluid. Our aim was two investigate the practicability and the value of free thyroxin (FT4), thyrotropin (TSH), 17alpha hydroxyprogesterone (17-OHP) and delta 4 androstenedione (Delta4A) measurement on amniotic fluid using commercially available assays for serum. FT4 and TSH are detectable at low levels in amniotic fluid. FT4 significantly increases from 2.1 pmol/L to 4.2 pmol/L while TSH significantly decreases from 0.27 mU/L to 0.12 mU/L during the second half of pregnancy. An increase in amniotic fluid TSH concentration contributes to the diagnosis of foetal hypothyroidy while the measurement of amniotic fluid FT4 is not informative in case of foetal goiter. 17-OHP and Delta4A are present in amniotic fluid at the same level as in serum. 17-OHP significantly decreases from 1.9 ng/mL to 1 ng/mL during the second half of pregnancy while Delta4A significantly increases from 0.5 ng/mL to 0.8 ng/mL. Absence of increase in their concentrations excludes any severe adrenal hyperplasia.

Comparability of method results and performance in a national external quality assessment scheme between 1993 and 2003 using thyroid associated analytes as examples.

Six thyroid analytes (free and total triiodothyronine and thyroxine, thyrotropin and thyroglobulin) have been followed up over a 10 year period in a national external quality assessment scheme (EQAS) organised by the Institute for Standardisation and Documentation in the Medical Laboratory (INSTAND). I. The following points were observed: II. The introduction of samples with properties similar to patient serum (filtered, recalcified defibrinated plasma without stripping) improved performance and inter-method comparability for the free thyroid hormones. III. In general, the performance in EQAS has improved over the past decade, an exception being thyroglobulin, where precision has improved at the expense of inter-method comparability. IV. Regular statistical analysis of EQAS data allows adjustment of target ranges to be made when necessary. V. Analytes which are not dependent on binding proteins--thyrotropin and the total thyroid hormones--give rise to similar performance when stripped and spiked plasma or recalcified non-stripped and spiked plasma is used as sample. VI. Whereas certain analytes have had a relatively constant number of participants over the past decade (total thyroid hormones), others have shown a drastic increase (free thyroxine from 67 to 620; thyrotropin from 295 to 724) reflecting the medical demand for the analytes.

Assay of free thyroxine and free triiodothyronine in fine-needle aspiration of thyroid nodules: a useful and low-cost assessment.

OBJECTIVE: To evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules. METHODS: We studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma. RESULTS: The free thyroxine (FT(4)) and free triiodothyronine (FT(3)) values were remarkably high in group 1 (mean, 5.5 +/- 0.53 ng/dL and 27.6 +/- 3.1 pg/mL, respectively; P<0.05 versus group 2 and group 4, the control group). The levels of FT(4) and FT(3) were very low in group 3 (<0.2 ng/dL and <1.0 pg/mL, respectively; P<0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT(4) and FT(3) (<0.2 ng/dL and <1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules. CONCLUSION: These results show that assay of FT(4) and FT(3) in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory.

Thyroid function testing in outpatients: are both sensitive thyrotropin (sTSH) and free thyroxine (FT4) necessary?

BACKGROUND AND OBJECTIVES: Despite improved thyroid function testing assays, appropriate use of these commonly ordered tests to detect thyroid dysfunction remains controversial. This study determined if a normal sensitive thyroid stimulating hormone (sTSH) test alone is sufficient to rule out thyroid dysfunction in outpatients. METHODS: This was a retrospective analysis of initial sTSH and free thyroxine index (FT4) tests ordered during a 26-month period. Test results were classified as concordant if both the sTSH and FT4 indicated the same findings (ie, euthyroid, hyperthyroid, or hypothyroid). The results were classified as discordant if the sTSH and FT4 did not indicate the same findings. RESULTS: There were 1,392 paired sTSH and FT4 results. Of 1,340 results classified as concordant (96.2%), 1,187 specimens were consistent with euthyroidism, 41 with hyperthyroidism, and 112 with hypothyroidism. Of the remaining 52 (3.8%) discordant results, 47 met the definition of subclinical thyroid dysfunction. Excluding these 47 results yielded a concordance rate of 99.6%. Of the 1,192 normal sTSH results, FT4 was low in two and high in three. If FT4 tests had not been ordered on the 1,192 specimens with normal sTSH levels, the savings over the study period would have been more than dollars 3,360. CONCLUSIONS: If the sTSH is normal, the likelihood of an abnormal FT4 is very small. sTSH alone is adequate to screen outpatients for thyroid dysfunction. Limiting FT4 tests to those with abnormal sTSH results will result in cost savings.

Long-term calorie restriction reduces energy expenditure in aging monkeys.

Calorie restriction to produce stable long-term adult body weight for approximately 10 years prevents obesity and diabetes in middle-aged rhesus monkeys. To determine whether this dietary regimen also alters energy metabolism, the doubly labeled water method was used to measure total daily energy expenditure. Six adult male rhesus monkeys, which had been calorie-restricted for more than 10 years, were compared to 8 control adult monkeys, which had been fed ad libitum for their entire lives. The calorie-restricted monkeys weighed less than the ad-libitum fed monkeys and had a lower lean body mass and lower fat mass. Total daily energy expenditure was lower in the calorie-restricted than in the ad-libitum fed monkeys, even when corrected for differences in body size using body weight (563 +/- 64 vs 780 +/- 53 kcal/d; p < .04), surface area (547 +/- 67 vs 793 +/- 56 kcal/d; p < .05), or lean body mass (535 +/- 66 vs 801 +/- 54 kcal/d; p < .02) as covariates. Thyroxine (T4) was reduced and the free thyroxine index was suggestively lower in the calorie-restricted monkeys whereas triiodothyronine (T3) was not significantly different. Activity in calorie-restricted monkeys was similar to that of a weight-matched younger adult comparison group. We conclude that the process of preventing obesity by long-term caloric restriction causes a significant and sustained long-term reduction in energy expenditure, even when corrected for lean body mass.

Alternative sequences of thyrotropin and free thyroxine assays for routine thyroid function testing. Quality and cost.

BACKGROUND: Current guidelines and practices for thyroid function testing are strongly affected by the usually higher patient billing charges and Medicare reimbursement for thyrotropin (TSH) vs free thyroxine (FT4) tests, despite their comparable direct costs. OBJECTIVE: Due to recently reduced laboratory costs, to reexamine the effectiveness and cost of alternative test sequences. METHODS: Alternative test sequences involve using the TSH test first, followed, if the TSH test result is abnormal, by the FT4 test; the FT4 test first, followed by the TSH test; and doing both tests together. We applied these strategies to consecutive patients referred for any thyroid function test to a health maintenance organization, a multispecialty fee-for-service group, a military hospital, and a commercial laboratory. Effectiveness was determined from a literature review. The cost was determined from direct costs and the distribution of diagnostic categories. RESULTS: The TSH and FT4 tests have similar sensitivities for detecting clinical hyperthyroidism and hypothyroidism. The TSH test detects subclinical function, and it monitors thyroxine treatment better; the FT4 test detects central hypothyroidism, and it monitors rapidly changing function better. Direct costs for both were equal, but charges for the TSH test were higher. The average direct cost per patient, starting with the FT4 test, was $4.61; starting with the TSH test, $5.90; and starting with both tests together, $6.50. Medicare reimbursements correlated poorly with costs. CONCLUSIONS: Starting with the TSH test and reflexing to the FT4 test provides a better first-line all-purpose sequence than the reverse. In managed care settings, the slightly higher direct cost of this approach is offset by greater clinical effectiveness. In fee-for-service settings, cost differences can be nearly eliminated by equalizing TSH and FT4 charges to reflect current direct-cost realities. Obtaining both tests together overcomes the disadvantages of each at a slightly higher direct cost.

Analytical and clinical assessment of a commercial kit for the simultaneous determination of free thyroxine and thyrotropin.

The SimulTRAC FT4/TSH kit (Becton Dickinson), allowing a simultaneous determination of free thyroxine (FT4) and thyrotropin (TSH), was assessed in terms of analytical quality and clinical performance. The results of a multicenter trial were included in this study to obtain a more complete and reliable information. The current validation procedures (ie evaluation of analytical imprecision and sensitivity, between-kit comparison of estimates and--limited to TSH--check of response linearity on dilution) demonstrated quite acceptable analytical characteristics for both the FT4 and the TSH tests. The diagnostic sensitivity and predictive value were derived for separate and combined tests from a relatively large number of cases (ie 401 euthyroids, 127 overt and 48 subclinical hypothyroids, 205 overt and 80 compensated hyperthyroids). The TSH test proved more effective than FT4 in discriminating both overt and subclinical dysfunctions, and, in this respect, the test association was found to add a little advantage--if any. However, the extension of the concepts of diagnostic efficiency to any combination of test results--favoured by their production in a single assay--provides a basis to establish diagnostic protocols and to predict costs and benefits of medical actions.

Assessment of response/error relationship and imprecision profile in immunoassay using computer simulation procedures.

Simulation procedures were applied to assess the response/error relationship (RER) and the imprecision profile (IP) for two model assays, a T4 RIA and a TSH IFMA both using duplicate samples. In order to define the reference functions, the mean data obtained in 10 successive experiments for dose/response curve (DR), RER and IP were employed. The following conclusions emerged from the study: (a) run sizes of ca. 100 duplicates can acceptably describe within-assay IPs, irrespective of the data distribution through the dose range; (b) the contribution of DR fitting error to the total variability of estimate can be disregarded in the case of small series but not for the larger ones; (c) the variability components related to the response error can be efficiently controlled by applying criteria based on RER parameters.

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer.

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T4 derivative that does not bind significantly to the thyroxine-binding proteins. We evaluated this RIA for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T4 assay, expressed as coefficient of variation, was 20% at 0.16 ng/dl, 6.9% at 0.55 ng/dl, 4.2% at 1.08 ng/dl, 5.3% at 2.29 ng/dl, and 6.3% at 3.18 ng/dl. A reference range for free T4 was established as 0.68-1.8 ng/dl, n = 171. The correlation coefficients (r) of a dialysis method and a free thyroxine index were 0.871 and 0.911, respectively. Free T4 correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition, 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T4, very low T3, and elevated rT3. We found this free T4 assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.