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Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease.

OBJECTIVE: To determine whether nonthyroidal disease of various causes and severity is associated with abnormalities in baseline serum concentrations of total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone [TSH]) in dogs believed to be euthyroid. DESIGN: Case-control study. ANIMALS: 223 dogs with confirmed nonthyroidal diseases and presumptive normal thyroid function, and 150 clinically normal dogs. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations were measured in dogs with confirmed nonthyroidal disease. Reference ranges for hormone concentrations were established on the basis of results from 150 clinically normal dogs. RESULTS: In dogs with nonthyroidal disease, median serum concentrations of total T4, total T3, and free T4 were significantly lower than those in clinically normal dogs. Median serum TSH concentration in sick dogs was significantly greater than that of clinically normal dogs. When stratified by severity of disease (ie, mild, moderate, and severe), dogs with severe disease had low serum concentrations of total T4, total T3, or free T4 more commonly than did dogs with mild disease. In contrast, serum TSH concentrations were more likely to remain within the reference range regardless of severity of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that serum total T4, free T4, and total T3 concentrations may be low (ie, in the hypothyroid range) in dogs with moderate to severe nonthyroidal disease. Serum TSH concentrations are more likely to remain within the reference range in sick dogs.

Animals↗

Influence of thyroxine and thyroxine with growth hormone and prolactin on splenocyte subsets and on the expression of interleukin-2 and prolactin receptors on splenocyte subsets of Snell dwarf mice.

A number of immune parameters were examined in Snell dwarf mice and compared with normal littermates. The number of splenocytes per gram of body weight were significantly decreased in dwarf animals, and the decrease was distributed throughout the CD4, CD8, B220, and MAC-1 subsets. The percentage of CD4 and CD8 splenocytes was markedly increased, and the percentage of B220 and MAC-1 splenocytes markedly decreased, in dwarf animals. In addition, the percentage of splenocyte T cells constitutively expressing interleukin-2 (IL-2) receptors and prolactin (PRL) receptors was decreased, with the CD4 subset presenting the most dramatic effect. The effects of replacing the hormones deficient in the Snell dwarf mouse (i.e., growth hormone [GH], prolactin [PRL], and thyroxine [T4] on the above immune parameters were also examined. The administration of T4 alone for 10 days corrected the defect in splenocyte cell numbers per grams body weight for both the CD4 and CD8 subsets, but only partially corrected the defect for the B220 and MAC-1 subsets. The addition of rbGH and rbPRL for the last 3 days of T4 injection had little additive effect on the number of CD4 and CD8 cells but increased the number of B220 and MAC-1 subsets to values comparable to those of normal animals on the basis of body weight. The decrease in the percentage of CD4 splenocytes in dwarf animals constitutively expressing IL-2R was partially corrected by T4 injection and completely corrected by the addition of rbGH and rbPRL for the last 3 days. The decrease in CD4 splenocytes constitutively expressing PRLR was partially corrected by T4 injection alone and the addition of rbGH and rPRL resulted in percentages comparable to that of normal animals. The results indicate that Snell dwarf animals are deficient in immune parameters and that the administration of the hormones lacking in this animal can correct the deficiencies.

Analysis of Variance↗

Assessment of serum thyroxine binding capacity-dependent biases in free thyroxine assays.

BACKGROUND: Free thyroxine (FT4) assays may exhibit biases that are related to serum T4 binding capacity (sBC). We describe two tests that can be used to assess the presence and magnitude of sBC-dependent biases in FT4 assays. METHODS: We used a direct equilibrium dialysis FT4 assay as the reference method and compared the results obtained with those of the FT4 assays under investigation, in patient sera having a wide range of sBC. We then compared the expected and observed FT4 results for sera diluted with an inert buffer. Because serum dilution causes a predictable decrease in sBC, an increasingly negative bias on progressive dilution is indicative of a sBC-dependent bias. RESULTS: The automated FT4 assay investigated (Vitros FT4) showed no demonstrable sBC-dependent bias by either test. CONCLUSION: These two tests can be used to screen for sBC-dependent biases in FT4 assays.

Bias↗

An increase of liver uptake of thyroxine, an initial step of an increased fecal loss of thyroxine in response to propylthiouracil in rats.

Propylthiouracil augmented fecal loss of thyroxine (T4), but methimazole was without effect in this respect in rats. In vitro uptake of labeled T4 by the liver was significantly enhanced by a small amount of propylthiouracil in the presence of dilute rat plasma. Methimazole was without effect under comparable conditions. In contrast, propylthiouracil and methimazole failed to affect in vitro uptake of labeled T4 by the kidney and diaphragm in the presence of dilute rat plasma. Since deiodination of T4 does not occur in the presence of dilute rat plasma, it is suggested that propylthiouracil specifically stimulates liver uptake of T4 as an initial step of an increase of biliary-fecal excretion of T4 in rats.

Animals↗

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants.

OBJECTIVE: To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs. DESIGN: Prospective case series. ANIMALS: 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs. RESULTS: Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs. CLINICAL IMPLICATIONS: Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.

Animals↗

[Dissociation between the effects of TSH and dibutyryl cAMP on thyroxine secretion by isolated thyroid cells. Similarity of actions on iodide uptake and thyroxine synthesis (author's transl)].

We have compared the effects of TSH and dibutyryl-cAMP (DBC) on three parameters of iodine metabolism in isolated hog thyroid cells: iodide uptake, thyroxine (T4) synthesis and T4 secretion. As WILSON, we observed a similarity between TSH (60 mU/ml) and DBC (3 mM) actions on iodide uptake and T4 synthesis. But DBC did not reproduce the TSH stimulation of T4 secretion. Since TSH increased T4 secretion in the presence of DBC, the lack of effect of DBC was not due to an alteration of the secretory process by DBC. The present observation might suggest that the stimulatory effect of TSH on T4 secretion by isolated thyroid cells is not mediated by the adenyl cyclase-cAMP system, or could indicate that DBC may not act like cAMP on some target enzyme systems.

Animals↗

Concentrations of free thyroxin and free triiodothyronine in serum of patients with thyroxin- and triiodothyronine-binding autoantibodies.

Between 1982 and 1989 we identified 47 subjects with spuriously increased concentrations of free thyroxin (FT4) or free triiodothyronine (FT3) related to autoantibody interference in analog FT4 and (or) FT3 methods. The incidence of autoantibody interference observed during one year (1988) was 1 in 2460. In the subjects identified, 51% and 11%, respectively, showed an increased binding of radiolabeled T4 or T3 analog alone; 38% had an increased binding of both. Of 36 patients tested, 71% had autoantibodies to thyroglobulin and microsomal fraction of the thyroid, 19% to microsomal fraction alone, and 9.5% to thyroglobulin alone. In eight subjects, spuriously increased FT4 concentrations were reported with the following FT4 methods (in decreasing order of interference): Coat-A-Count, Amerlex-M, Amerlite, Seria, Magic Lite, Amerlex-MAB. In the same eight subjects, Amerlex-M and Seria reported spuriously increased concentrations of FT3.

Adolescent↗

Binding of labeled thyroxin analog to serum proteins evaluated after radioimmunoassay of free thyroxin.

In ambulatory patients, assay of free thyroxin (FT4) in serum correlates well with thyroid status and with results obtained by equilibrium dialysis. The validity of FT4 results has been questioned mainly in euthyroid patients with altered concentrations of thyroid hormone-binding proteins, as in nonthyroidal illness, hereditary analbuminemia, familial dysalbuminemic hyperthyroxinemia (FDH), and the presence of iodothyronine-binding antibodies. I present here a study of the binding of [125I]T4-derivative to serum proteins in the supernate, which is ordinarily discarded after determination of FT4 by one-step radioimmunoassay with dextran-coated charcoal used to separate the free and bound fractions. The results are expressed as a ratio, with results for a normal serum pool as reference. The average ratio was high in hyperthyroid subjects, 1.26 (SD 0.12, n = 25), and in hypoalbuminemia, 1.20 (SD 0.10, n = 15), and low in FDH, 0.62 (SD 0.11, n = 9), and hypothyroid subjects, 0.90 (SD 0.06, n = 20). In normal individuals it was 0.98 (SD 0.05, n = 30). Determination of the analog-binding rate complements the FT4 result and allows for the recognition of cases with abnormal binding by serum proteins, without recourse to other tests recommended for thyroid-function studies.

Blood Proteins↗

[Thyroxine vs iodine and thyroxine. Comparison of the TSH suppression test].

In a crossover study 20 subjects (12 with non-toxic goiter) were given 150 micrograms levo-thyroxine (LT4) or a combination of 100 micrograms LT4 and 100 micrograms iodide daily for 8 weeks. Group I took 150 micrograms LT4 and group II the combination. After 4 weeks the two groups switched medications. A clinical examination, an intravenous TRH test and thyroid sonography were performed before the start of the study and 4 and 8 weeks thereafter. 150 micrograms LT4 daily resulted in significantly higher TSH suppression than the combination. A decrease in thyroid volume from 45 ml (mean range 24-85) to 26 ml (17-70 ml) was registered after as little as 4 weeks' therapy in 12 of 20 subjects with goiter.

Adult↗

Free thyroxin by radioimmunoassay: evaluation of a new direct method involving a radiolabeled thyroxin analog.

We present here the first performance evaluation of a new direct method for free thyroxin (T4) in serum by radioimmunoassay, with use of coated tubes and a radiolabeled T4 analog (Diagnostic Products Corp.). The assay is precise and robust: within-run imprecision (CV), 3.1-6.6%; between-run imprecision, 4.0-7.9%; no demonstrable variation between technologists irrespective of experience with the method. No outliers were observed when we compared the free T4 results with serum total T4. Reference values are reported for a total of 1243 euthyroid subjects; there was no significant age effect on serum free T4 in women 26 to 72 years old. The biological variation was about +/- 35% of the mean (2 SD). Free T4 results are the same for serum and plasma. The assay performs well in hypothyroidism and hyperthyroidism, and distinguishes individuals with thyroid disease from normal individuals. Free T4 values in women taking oral contraceptives are normal. Depressed results were often observed in acute nonthyroidal illness and continuing pregnancy. These results were directly comparable with those of another commercial direct radiolabeled-T4 analog kit for free T4.

Adult↗

Salivary thyroxine as an estimate of free thyroxine: concise communication.

To test the hypothesis that the levels of salivary thyroxine (T4) reflect those of circulating free T4, we developed a radioimmunoassay (RIA) sensitive to low levels of T4. Concurrent saliva and serum samples were obtained from 32 euthyroid volunteers, ages 19-64. Salivary and serum T4 and cortisol levels were measured by RIA. Salivary albumin was measured by nephelometry. Salivary T4 levels were higher than predicted, 4.2-35 ng/dl (normal range 0.6-2.0). No correlation was found between salivary T4 and serum levels of free T4 and total T4 but there was a significant correlation between salivary T4 and albumin (r = 0.82). Salivary cortisol levels agreed with reported results and showed no correlation with salivary albumin. We conclude that salivary levels of drugs and hormones may be strongly affected by protein binding, and caution must be exercised in using salivary levels as an estimate of circulating free levels.

Adult↗

Comparison of the effect of a single oral L-thyroxine dose (150 micrograms) in tablet and in solution on serum thyroxine and TSH concentrations.

150 micrograms of L-thyroxine were administered to each of 14 euthyroid goitrous patients orally between 7:30 and 8:30 a.m. after fasting overnight. The L-T4 dose given was one and half tablets of the drug "Eutirox" (L-T4 tablet of 100 micrograms distributed by Bracco, Milan, Italy) or one and half ml of the solution "Tiroxen" (solution containing 100 micrograms/ml of L-T4 distributed by Laboratori Baldacci, Pisa, Italy). Two studies (one with tablet and one with solution) were performed on each patient. The tablet or the liquid form of L-T4 were administered in random order. In each study a blood sample for serum hormone determination was drawn immediately before L-T4 administration, then 30 minutes later and every hour up to the fifth hour after. The second study was performed in similar fashion later. The mean serum TT4 concentration value at any time was very similar in the two studies, thus showing the same time course after the administration of solution and the tablet formulation. The mean basal TT4 value (9.07 +/- 0.56 and 8.90 +/- 0.73 micrograms/dl respectively) increased significantly at the first and second hours. The highest value was reached at the second and at the third hour after the solution (11.15 +/- 0.58 micrograms/dl) and the tablet (11.81 +/- 0.78 micrograms/dl) respectively. Subsequently, the mean TT4 values remained significantly higher than basally over the entire 5 hours. The FT4 mean serum concentration at all times were very similar in the two studies and showed the same time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Total thyroxine (T4) and free thyroxine (FT4) in hypothyroidism and nonthyroid diseases of dogs].

In 1548 dogs total and free thyroxine were determined. 559 of these dogs had been divided into 13 groups: 130 were healthy dogs, 22 suffered from hypothyroidism, two from hyperthyroidism, 405 from various other internal diseases. The other 989 dogs did not belong to one of the groups of interest or could not be attached to a certain group. In all hypothyroid dogs FT4-values were hypothyroid, whereas T4 was hypothyroid just in 16 cases; the other six values were located in the "gray area", which is supposed to be 1.2 to 1.8 micrograms/dl (15 to 23 nmol/l). Many dogs with other diseases expressed low T4- and/or FT4-values, too. Low hormone values could be measured especially in case of severe diseases. If the clinical symptoms corresponded to hypothyroidism and both T4 and FT4 were situated in the hypothyroid area, hypothyroidism is generally assumed. In all the other cases further diagnostic procedures must be performed.

Alopecia↗