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Summary

Serum iodothyronine concentrations from 4,064 samples submitted for monitoring of thyroid replacement therapy were evaluated in a retrospective study. After exclusion of samples because of the presence of 3,5,3’ triiodothyronine (T3) autoantibodies, insufficient numbers of dogs on some commercial preparations or medication with corticosteroids or synthetic T3 preparations, data from 2,674 dogs remained. Data were analyzed by using information on dose, time after dosing, commercial product, and once-a-day or twice-a-day dosing regimens. Serum total thyroxine (T4) and total T3 and estimates of free T4 and free T3 were significantly high in serum from dogs given higher doses of synthetic L-thyroxine orally. Doubling the oral dosage did not double the serum iodothyronine concentrations, perhaps because of poor absorption or more rapid catabolism of the hormones at higher L-thyroxine doses.

Wide variation in the therapeutic hormone concentrations was found. Some dogs given low dosages of L-thyroxine had normal iodothyronine concentrations whereas some others given higher dosages had low normal to low concentrations. Monitoring the serum concentrations is an objective way to ensure adequate concentrations for successful therapy. When a therapeutic trial is used as a diagnostic procedure, one should not rule out hypothyroidism unless a therapeutic monitoring sample has indicated that replacement dose and absorption of the exogenous iodothyronine has been adequate.

Thyroid hormone concentrations peaked at 4 to 6 hours after oral administration of L-thyroxine for once-a-day and twice-a-day dosage regimens. Higher concentrations were achieved with once-a-day than with twice-a-day regimens at the same total daily dose. Because 2 of the lower peaks occurred per day with twice-a-day dosing, total target tissue exposure to the iodothyronines appeared to be similar to the once-a-day exposure. In general, dogs receiving the veterinary preparation of sodium levothyroxine had higher serum concentrations of iodothyronines than did dogs receiving a commonly used human preparation or generic preparations.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

Articular cartilage explants from 3 horses were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan on proteoglycan biosynthesis. Cultures were exposed to concentrations of 0, 50, or 200 μg of the drug/ml for either 2 days or 6 days, and labeled with 35S, before measuring the content of sulfated proteoglycan in the culture media and in extracts of cartilage. In a second experiment, the explants were incubated with the isotope and subsequently exposed to the same concentrations of the polysulfated glycosaminoglycan for 4 days. Subsequently, the amount of remaining labeled proteoglycan was determined. Gel filtration chromatography was used to compare the hydrodynamic size of proteoglycans from the cartilage explants in each experiment.

Polysulfated glycosaminoglycan caused a dose-dependent depression of sulfated proteoglycan synthesis, which was statistically significant after 6 days of exposure. Radioactive proteoglycan content in explants was similar in the experiment involving isotopic labeling prior to exposure to the drug. Proteoglycan monomer size was similar in all treatment groups. It was concluded that polysulfated glycosaminoglycan caused a modest depression in proteoglycan synthesis, had little effect on endogenous proteoglycan degradation, and did not influence the size of sulfated proteoglycans synthesized by normal equine chondrocytes in explant culture.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine prevalence of thyroid hormone autoantibodies (THAA) in serum of dogs with clinical signs of hypothyroidism.

Design—Cohort study.

Sample Population—287,948 serum samples from dogs with clinical signs consistent with hypothyroidism.

Procedure—Serum THAA were detected by use of a radiometric assay. Correlation and X 2 analyses were used to determine whether prevalence varied with breed, age, sex, or body weight. Only breeds for which ≥ 50 samples had been submitted were used for analysis of breed prevalence.

Results—Thyroid hormone autoantibodies were detected in 18,135 (6.3%) samples. The 10 breeds with the highest prevalence of THAA were the Pointer, English Setter, English Pointer, Skye Terrier, German Wirehaired Pointer, Old English Sheepdog, Boxer, Maltese, Kuvasz, and Petit Basset Griffon Vendeen. Prevalence was significantly correlated with body weight and was highest in dogs between 2 and 4 years old. Females were significantly more likely to have THAA than were males.

Conclusions and Clinical Relevance—Thyroid hormone autoantibodies may falsely increase measured triiodothyronine (T3) and thyroxine (T4) concentrations in dogs; results suggest that T3 concentration may be falsely increased in approximately 57 of 1,000 dogs with hypothyroidism and that T4 concentration may be falsely increased in approximately 17 of 1,000 dogs with hypothyroidism. Results also suggested that dogs of certain breeds were significantly more or less likely to have THAA than were dogs in general. (J Am Vet Med Assoc 2002;220:466–471)

Full access
in Journal of the American Veterinary Medical Association

Summary

Five studies were performed to determine factors affecting progesterone concentration in skim milk. Results of the first study indicated that progesterone concentration was higher in skim milk of samples kept 16 hours in an ice bath (0 C) than of those left at room temperature (21 C). In the second study, this temperature effect was found to be reversible, with skim milk progesterone concentration increasing when whole milk samples were cooled prior to centrifugation. In the third study, [3H]-labeled progesterone was used to determine the relationship between fat content of foremilk (the first milk obtained from the teats), midmilk (milk obtained midway through milking), and strippings (milk obtained immediately after milking machines have been removed) samples and temperature (4 C and 21 C) on the percentage of progesterone in the skim milk fraction. The relationship between percentage of butterfat and percentage of progesterone in skim milk was linear when the log of these variables was used for calculations. In the fourth study, assayable progesterone in the skim milk fraction of foremilk, midmilk, and strippings was affected by temperature. In the fifth study, a multiple-regression procedure was used to determine the amount of variation in percentage of radioactive progesterone in the skim milk - fraction. Independent variables (whole milk butterfat and temperature of incubation [1, 3, 13, 22, 37, and 50 C]) and the natural log of each variable, were entered into a step-wise multiple-regression analysis. The log of the temperature and percentage of butterfat of whole milk at the time of centrifugation accounted for 89.2% (r 2 = 0.892) of the variation in the log of the progesterone concentration in the skim milk fractions. The equation describing this relationship was: log percentage of progesterone in the skim milk fraction = 4.046 — 0.144 × (log of temperature of whole milk sample) × 0.688 × (log percentage of butterfat in whole milk sample). The loss of progesterone from skim milk fractions of warm whole milk samples is possibly a physical phenomenon dependent on the temperature of the sample and its percentage of butterfat. A nomograph was created to allow others to use these variables in making adjustments in progesterone concentrations.

Free access
in American Journal of Veterinary Research

Summary

The effect that 5 consecutive days of treatment with dexamethasone (0.04 mg/kg of body weight, IM, q 24 h) would have on baseline concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3), free T3 (FT3), and free T4 (FT4), and on response to thyroid-stimulating hormone (tsh) administration was determined in 12 clinically normal horses. Results of tsh response tests indicated that the horses could be placed into 2 groups: in 6 horses (group A), T4 concentration after administration of tsh was more than twice the baseline concentration; in the other 6 horses (group B), T4 concentration 6 hours after administration of tsh was less than twice the baseline concentration. Baseline serum concentrations of T3, T4, rT3, FT3, and FT4, were not significantly different between group-A and group-B horses. In both groups of horses, serum T3, T4, rT3, and FT4, concentrations were significantly increased 6 hours following tsh administration, compared with baseline concentrations. Treatment with dexamethasone resulted in significant (P < 0.05) increases in baseline concentrations of rT3 and FT3 in group-A horses and baseline concentrations of rT3 in group-B horses. The response to tsh administration following dexamethasone treatment appeared to be blunted with significant (P < 0.05) increases only in T3, T4, and FT4, concentrations in group-A horses and FT4, concentration in group-B horses. The magnitude of change in serum FT3 concentration in response to tsh administration was significantly less (P = 0.05) following dexamethasone treatment, compared with magnitude of change prior to dexamethasone treatment. Results suggested that tsh response testing may not be as valuable as once thought for diagnosing hypothyroidism in horses or for differentiating thyroidal from nonthyroidal illness.

Free access
in Journal of the American Veterinary Medical Association

Summary

Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered l-thyroxine. The dogs were treated with 44, 22, and 11 μg of l-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (Css) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of anova.

Concentration at steady state was highest for dogs of the 44-μg/kg of body weight once-daily group and was lowest for dogs of the group given 11 μg/kg in 2 daily doses. Single daily administration resulted in higher Css, except at the 22-μg/kg/d dosage. Clearance was faster for the 22- and 44-μg/kg/d dosages than for the 11-μg/kg/d dosage. The half-life (t1/2) and mean residence time (mrt) also were shorter for the 44-μg/kg/d dosage, possibly indicating more rapid elimination of the drug at higher doses and dose-dependent kinetics. Perhaps, as the dogs’ metabolism increased with higher iodothyronine concentrations, hormone degradation was accelerated. Interval (divided vs single dose) caused some expected changes: maximal concentration was higher and minimal concentration was lower when single administration was used. These undulations resulted in iodothyronine concentrations above the physiologic range for a number of hours, whereas concentration closer to physiologic ranges was achieved by use of divided doses. Delayed absorption (lag time) was seen in 37 of the 72 data sets, but was generally short, about 0.25 hour. Mean time to maximal concentration was 3 to 4 hours. At the higher dosages, serum total T4 concentration was high normal or above normal during most of the time after l-thyroxine administration, but serum concentration of total 3,5,3′-triiodothyronine did not remain within the normal range until the 44-μg/kg/d dosage was used. The customary dosage of 22 μg/kg/d (0.1 mg/10 lb/d) may not be adequate for most dogs. Pharmacokinetic variables appear to be highly dependent on the individual dog. Those with rapid absorption and higher concentration tended to have these characteristics at each dosage in this study. The pharmacokinetic variables, therefore, appear to be highly individualized, and dosages recommended for treatment of hypothyroidism should be considered to be only a starting point for the average dog. To avoid underdosing or overdosing, monitoring of treatment to adjust dose for individual dog kinetic variables seems to be imperative.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate a thyroglobulin autoantibody (TgAA) assay and determine a diagnostic threshold.

Sample Population

Serum samples from dogs with various endocrine abnormalities and from 30 obese adult female Beagles.

Procedure

TgAA were determined by use of the ELISA. Six experiments were done: 1, definition of positive results for TgAA using samples from normal and T3 autoantibody (T3AA) positive dogs; 2, establishment of prevalence of positive results in 91 clinically normal dogs; 3, evaluation of positive results for sera from dogs with nonthyroidal illnesses; 4, testing of samples from dogs with primary hypothyroidism but absence of T4AA or T3AA, or both; 5, determination of prevalence of false-negative results in dogs that are T4AA and/or T3AA positive, which were (18 dogs) or were not (22 dogs) receiving L-thyroxine replacement therapy; and 6, examination of thyroid biopsy specimens from 18 dogs (8 TgAA positive and 10 TgAA negative).

Results

Positive results were defined as at least twice (200%) the optical density of the negative-control sample. False-positive results were obtained for only 3.4% of 146 dogs with nonthyroidal illness. Thirty-seven percent of dogs with primary hypothyroidism, but no evidence of T4AA or T3AA, or both, were TgAA positive. False-negative results were found in 1 of 22 and 2 of 18 T3AA-positive dogs with and without thyroid replacement therapy, respectively. Thyroid biopsy specimens from 8 TgAA-positive dogs had evidence of lymphocytic thyroiditis, whereas those from 10 TgAA-negative dogs did not.

Conclusion and Clinical Relevance

The assay is sensitive and specific for identification of lymphocytic autoimmune thyroiditis in dogs, and has potential for aiding early diagnosis of thyroiditis in dogs and identifying dogs likely to perpetuate hypothyroidism in breeding programs. (Am J Vet Res 1998;59:951–955)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate benign familial hyperphosphatasemia involving serum alkaline phosphatase (SAP) in pups.

Design

Pups with markedly increased SAP activity were evaluated and compared with unaffected siblings, and with other unaffected Siberian Husky pups from the same colony.

Animals

8 related litters of Siberian Husky pups (n = 56).

Procedure

At ages 11 and 16 weeks, pups were given physical examinations and blood was obtained for hematologic and serum biochemical analyses (including electrolytes and isoenzymes of alkaline phosphatase), ionized calcium concentration, and serum parathyroid hormone concentration. Diet, growth and health performance, skeletal radiographs, and genealogical data also were evaluated.

Results

Of 42 pups tested, 17 had markedly high total SAP values. Mean total SAP activity of affected pups at ages 11 and 16 weeks was over 5 times greater than mean total SAP activity of unaffected siblings and other unaffected Siberian Husky pups of the same age (P <0.001). Clinical, radiologic, and biochemical evaluation of the subjects revealed no other abnormal findings. The source of the increased SAP activity was characterized in 5 affected pups as bone isoenzyme. The mode of inheritance could not be deduced from the data, but the trait clearly is familial and autosomal.

Conclusion

The condition described in the family of Siberian Huskies bears similarity to human benign, persistent, familial hyperphosphatasemia.

Clinical Relevance

Benign familial hyperphosphatasemia should be considered in the differential diagnosis of markedly increased SAP activity in young dogs. (Am J Vet Res 1996; 57:612–617)

Free access
in American Journal of Veterinary Research

SUMMARY

Six healthy, adult horses, with normal (mean ± sem) baseline serum concentrations of total triiodothyronine (T3,1.02 ± 0.16 nmol/L), free T3 (FT3,2.05 ± 0.33 pmol/L), total thyroxine (T4, 19.87 ± 1.74 nmol/L), free T4 (FT4, 11.55 ± 0.70 pmol/L), total reverse T3 (rT3, 0.68 ± 0.06 nmol/L), and cortisol (152.75 ± 17.50 nmol/L), were judged to be euthyroid on the basis of response to a standardized thyroid-stimulating hormone response test. Serum concentrations of T3, FT3, T4, FT4, rT3, and cortisol were determined immediately before and every 24 hours during a 4-day period of food deprivation, when water was available ad libitum. Similar variables were measured 72 hours after refeeding.

Decreases (to percentage of baseline, prefood deprivation value) in circulating T3 (42%), T4 (38%), FT3 (30%), and FT4 (24%) concentrations were maximal after 2, 4, 2, and 4 days of food deprivation, respectively (P < 0.05). Increases (compared with baseline, prefood deprivation value) in rT3 (31%) and cortisol (41%) concentrations were maximal after 1 and 2 days of food deprivation, respectively (P < 0.05). Refeeding resulted in increase in serum T4 and FT4, and decrease in rT3 and cortisol concentrations toward baseline values, after 72 hours (P < 0.05). Re-feeding did not effect a return of T3 or FT3 concentration to baseline values after 72 hours (P < 0.05).

Food deprivation appears to cause changes in serum concentrations of T3, FT3, T4, FT4, rT3, and cortisol in horses that are similar to those in human beings. This effect of food deprivation should be considered when results of serum thyroid hormone and cortisol assays are interpreted in the face of clinical disease. These results further emphasize the invalidity of making a clinical diagnosis of hypothyroidism on the basis of baseline, serum thyroid hormone concentrations in horses, especially if the horses have been anorectic or inappetent.

Free access
in American Journal of Veterinary Research

Summary

Administration of triiodothyronine (liothyronine, 15 μg, q 8 h, for 6 treatments) caused marked decrease in serum concentration of thyroxine (T4) and estimates of free T4 (fT4) concentration in clinically normal cats. A prospective clinical study was done to evaluate the use of this suppression test for diagnosis of hyperthyroidism in cats with clinical signs suggestive of the disease, but lacking high serum concentration of iodothyronines.

Twenty-three cats were confirmed as hyperthyroid on the basis of histologic changes in the thyroid gland or clinical improvement in response to administration of methimazole. Mean ± sd serum concentration of T4 (34.3 ± 12.7 to 31.3 ± 11.5 nmol/L) and estimate of fT4 concentration (26.6 ± 6.4 to 25.6 ± 6.9 pmol/L) did not change after administration of liothyronine to these cats. Twenty-three cats were classified as nonhyperthyroid by histologic confirmation of other disease, abnormal results of other diagnostic tests that strongly supported primary disease other than hyperthyroidism, or spontaneous remission of weight loss without treatment. Mean ± sd serum concentration of T4 (27.9 ± 10.3 to 11.7 ± 6.4 nmol/L) and estimate of fT4 concentration (21.7 ± 5.4 to 10.4 ± 4.4 pmol/L) decreased significantly (P < 0.001) in response to administration of liothyronine.

Discriminant analysis was used to identify variables from iodothyronine assays (eg, absolute concentration of T4 or absolute estimate of fT4 concentration, or changes of T4 or fT4 concentration) that provided the best diagnostic sensitivity and specificity. The endocrine end points that best differentiated hyperthyroid vs nonhyperthyroid cats were the concentration of T4 or estimate of fT4 concentration in serum obtained after liothyronine administration and predictive values ues calculated from postliothyronine serum concentration of T4 or fT4 and percentage decrease of T4 concentration. Difference in diagnostic sensitivity among endocrine end points compared was not apparent. Use of postliothyronine estimate of fT4 concentration alone or as part of a predictive value improved diagnostic specificity for differentiation of hyperthyroid vs non-hyperthyroid cats (P ≤ 0.081).

Results of this study further confirm existence of hyperthyroidism in cats that do not have high serum concentration of iodothyronines. We concluded that the triiodothyronine suppression test is a safe and accurate test for diagnosis of hyperthyroidism in cats with suggestive clinical signs of the disease, but lacking high serum concentration of iodothyronines.

Free access
in Journal of the American Veterinary Medical Association