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  • Author or Editor: Robert J. Kemppainen x
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Abstract

Objective—To determine whether inoculation of healthy dogs with a recombinant peptide containing 3 copies of ACTH would result in the production of antibodies against ACTH and whether this would affect pituitary-adrenocortical function.

Animals—8 healthy dogs.

Procedures—A recombinant peptide consisting of 3 copies of ACTH fused to a T-helper cell epitope was produced in Escherichia coli. The protein was inoculated into 4 dogs at 4-week intervals (total of 3 inoculations/dog). Four control dogs received inoculations of PBS solution mixed with adjuvant. Blood samples were collected for determination of antibody titers against ACTH and for measurement of basal and ACTH-stimulated plasma cortisol concentrations.

Results—Inoculation with the ACTH vaccine resulted in production of anti-ACTH antibodies in all 4 dogs. Titers were initially high but declined by 15 weeks after the initial inoculation. Basal cortisol concentrations were unaffected by inoculation with the ACTH vaccine. Plasma cortisol concentrations in response to ACTH stimulation were reduced at 12 weeks, but not at 15 weeks, after the first inoculation.

Conclusions and Clinical Relevance—Inoculation of dogs with a recombinant ACTH vaccine resulted in the production of antibodies against the hormone. Anti-ACTH titers were initially high but were not sustained. The only detectable endocrine effect in treated dogs was a reduction in cortisol concentration in response to ACTH stimulation in 2 of 4 dogs at 12 weeks after the first inoculation. The effect of vaccine administration on the pituitary-adrenal system was subtle and transient.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare results obtained from assay of total thyroxine (T4) concentration in serum of dogs and cats by use of 4 methods.

Sample Population—Serum samples obtained from 98 dogs and 100 cats and submitted by veterinarians to an endocrine testing laboratory.

Procedure—Total T4 concentration was determined in each sample by use of 4 assay methods. Assay methods included a radioimmunoassay (RIA) marketed for use in dogs, an RIA for use in humans, a chemiluminescent enzyme immunoassay for use in humans, and an in-house ELISA.

Results—Total T4 concentrations obtained by use of all methods were significantly correlated. Bias-plot comparison revealed similar good overall agreement. Total T4 concentrations determined by use of the RIA marketed for use in dogs were generally lower than concentrations measured by use of the other methods. Clinical comparisons were made by evaluation of the T4 results in the context of the reference range recommended by each laboratory. A difference was found for clinical comparisons on the basis of T4 assay method when used to identify dogs as possible hypothyroid suspects. This difference was related more to the reference range used than to the absolute T4 value. The number of hyperthyroid-suspect cats with T4 values greater than the reference range was the same for each of the 4 assay methods.

Conclusions and Clinical Relevance—Total T4 concentrations determined in dogs and cats by use of 4 commonly used methods provided similar and consistent results.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare serum total thyroxine (T4) concentrations obtained with an in-house ELISA and a validated radioimmunoassay (RIA).

Design—Laboratory trial.

Sample Population—50 canine and 50 feline serum samples submitted for measurement of total T4 concentration with the RIA; samples were selected to represent a wide range of concentrations (< 6 to 167 nmol/L).

Procedure—Results of the ELISA and RIA were compared by calculating correlation coefficients, examining linearity, determining bias and precision, and evaluating clinical interpretations.

Results—Correlation coefficients for results of the 2 methods were 0.84 for the canine samples and 0.59 for the feline samples. Examination of bias plots revealed large variations in ELISA results, compared with RIA results. For the feline samples, the ELISA consistently overestimated total T4 concentration obtained with the RIA. When results of the 2 methods were categorized (low, borderline low, normal, borderline high, or high), results were discordant for 24 (48%) and 29 (58%) of the canine samples and for 18 (36%) and 28 (56%) of the feline samples (depending on whether borderline high ELISA results were considered normal or high). Reliance on results of the ELISA would have led to inappropriate clinical decisions for 31 (62%) canine samples and 25 (50%) feline samples. The ELISA coefficients of variation for the pooled canine and feline samples were 18 and 28%, respectively.

Conclusions and Clinical Relevance—Substantial discrepancies between ELISA and RIA results for T4 concentrations were detected. Thus, we concluded that the in-house ELISA kit was not accurate for determining serum total T4 concentrations in dogs and cats. (J Am Vet Med Assoc 2002;221:243–249)

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the effects of oral administration of controlled-ileal-release (CIR) budesonide on the pituitary-adrenal axis in dogs with a normal gastrointestinal mucosal barrier.

Animals—10 healthy dogs.

Procedures—5 dogs received CIR budesonide orally once daily for days 1 through 28, and 5 dogs received placebo. Treatment group dogs that weighed < 18 kg received 2 mg of CIR budesonide; treatment group dogs that weighed ≥ 18 kg received 3 mg of CIR budesonide. In the treatment and placebo groups, there were 3 and 2 dogs, respectively, that weighed > 18 kg. Plasma cortisol concentration before and after ACTH stimulation, basal plasma endogenous ACTH concentration, and body weight were measured on days 0, 7, 14, 21, 28, and 35. Serum biochemical analysis, CBC determination, and urinalysis were performed on days 0, 28, and 35. On days 7, 14, and 21, serum ALP and ALT activities, serum glucose concentration, and urine specific gravity were obtained in lieu of a full hematologic evaluation and urinalysis.

Results—Basal and post-ACTH stimulation plasma cortisol concentrations and plasma endogenous ACTH concentration were significantly suppressed by treatment. No other variables were altered over the course of the study.

Conclusions and Clinical Relevance—Budesonide suppresses pituitary-adrenal function in dogs with normal gastrointestinal integrity, whereas other variables often affected by glucocorticoids were not altered by a 4-week treatment course. Budesonide may be a good alternative to traditional cortico-steroids if used short-term for acute exacerbations of inflammatory bowel disease.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of oral administration of anti-inflammatory dosages of prednisone for 28 days on serum aldosterone, cortisol, and electrolyte concentrations in clinically normal dogs.

Animals—10 dogs.

Procedures—On days 1 through 28, 5 dogs received prednisone (0.55 mg/kg, PO, q 12 h) and 5 dogs received similar treatments with a placebo (empty capsules). Serum cortisol and aldosterone concentrations before and after ACTH stimulation testing and serum electrolyte concentrations were measured before (day 0 [baseline]), during (days 7, 14, 21, and 28), and after (days 35 and 42) treatment.

Results—At baseline, variables did not differ between the 2 groups. Serum cortisol concentrations before and after ACTH stimulation testing did not change from baseline values in placebo-treated dogs. In prednisone-treated dogs, serum chloride and corrected chloride concentrations were significantly lower on days 7, 14, 21, and 28 and serum bicarbonate concentrations were significantly higher on days 14, 21, and 28, compared with baseline values. Serum cortisol concentrations before and after ACTH stimulation testing were significantly lower than baseline values during prednisone treatment. Serum aldosterone concentration after ACTH stimulation testing was significantly lower than baseline on day 35 (ie, 1 week after discontinuation of prednisone treatment) but returned to baseline by day 42 in prednisone-treated dogs.

Conclusions and Clinical Relevance—Administration of anti-inflammatory dosages of prednisone caused significant changes in serum chloride, bicarbonate, and cortisol concentrations in clinically normal dogs. Although ACTH-stimulated serum aldosterone concentrations were unchanged from baseline during glucocorticoid administration, values decreased after treatment cessation but quickly returned to baseline values.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To assess effects of major abdominal surgery on serum cortisol and aldosterone and plasma canine ACTH (cACTH) concentrations.

ANIMALS 39 healthy dogs undergoing laparotomy during veterinary student surgical laboratories.

PROCEDURES Blood samples were obtained before and at completion of surgery. Serum cortisol and aldosterone and plasma cACTH concentrations were measured by use of validated radioimmunoassays. Changes in concentrations (postoperative concentration minus preoperative concentration) were calculated. Data were analyzed by use of the Wilcoxon signed rank test, Pearson correlation analysis, and Mann-Whitney rank sum test.

RESULTS Cortisol, aldosterone, and cACTH concentrations increased significantly from before to after surgery. Although cortisol and aldosterone concentrations increased in almost all dogs, cACTH concentrations decreased in 6 of 32 (19%) dogs. All dogs had preoperative cortisol concentrations within the reference range, but 24 of 39 (62%) dogs had postoperative concentrations above the reference range. A correlation between the change in cACTH concentration and the change in cortisol concentration was not detected.

CONCLUSIONS AND CLINICAL RELEVANCE Laparotomy caused a significant increase in serum cortisol and aldosterone concentrations. In most dogs, but not all dogs, plasma cACTH concentrations increased. Lack of correlation between the change in cACTH concentration and the change in cortisol concentration suggested that increased postoperative cortisol concentrations may have been attributable to ACTH-independent mechanisms, an early ACTH increase that caused a sustained cortisol release, or decreased cortisol clearance. Further studies are indicated to evaluate the effects of various anesthetic protocols and minimally invasive surgical techniques on the stress response.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone.

Design—Retrospective and prospective case series.

Animals—14 dogs.

Procedures—Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples.

Results—Total serum thyroxine concentrations were high (median, 8.8 μg/dL; range, 4.65 to 17.4 μg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 μg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 μg of thyroxine/g.

Conclusions and Clinical Relevance—Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine testing protocols used by board-certified internists and dermatologists for diagnosis of hyperadrenocorticism (HAC) in dogs.

Design—Survey.

Study Population—Board-certified internists and dermatologists.

Procedure—A questionnaire was mailed to 501 specialists to gather information pertaining to diagnosis of HAC.

Results—206 surveys were returned. Only 26% of respondents indicated they would screen a dog for HAC if the dog had only a few laboratory abnormalities consistent with HAC and no clinical signs consistent with the disease; 31% indicated they would not, and 43% indicated they would sometimes. Overall, 55% of respondents indicated they preferred to use the lowdose dexamethasone suppression test for routine screening of dogs suspected to have HAC. However, many respondents indicated they would use a different screening test than usual in particular circumstances. Sixty-eight percent of respondents indicated they would perform a second screening test for confirmation if results of an initial screening test were positive but there were few clinical or laboratory abnormalities consistent with HAC. Most respondents used some sort of test to differentiate pituitary-dependent HAC from HAC secondary to an adrenal tumor (AT), but no 1 test was clearly preferred. Ultrasonography was commonly used, whereas computed tomography and magnetic resonance imaging were not, even if available.

Conclusions and Clinical Relevance—Results suggest that the low-dose dexamethasone suppression test is the test most commonly used to screen dogs for HAC but that other tests may be used in certain circumstances. A variety of tests were used to differentiate pituitary-dependent HAC from HAC secondary to an AT. (J Am Vet Med Assoc 2002;220:1643–1649)

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare adrenal gland stimulation achieved following administration of cosyntropin (5 μg/kg [2.3 μg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism.

Design—Clinical trial.

Animals—9 healthy dogs and 9 dogs with hyperadrenocorticism.

Procedures—In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration.

Results—In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration.

Conclusions and Clinical Relevance—Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 μg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV).

Design—Cohort study.

Animals—31 ill dogs admitted to an intensive care unit (ICU) at Washington State University or the University of Pennsylvania; all dogs had acute critical illness for < 48 hours prior to admission.

Procedures—Baseline and ACTH-stimulated serum cortisol concentrations and baseline plasma ACTH concentrations were assayed for each dog within 24 hours after admission to the ICU. The change in cortisol concentrations (Δ-cortisol) was calculated for each dog. Morbidity and mortality data were recorded for each patient.

Results—Overall, 17 of 31 (55%) acutely critically ill dogs had at least 1 biochemical abnormality suggestive of adrenal gland or pituitary gland insufficiency. Only 1 (3%) dog had an exaggerated response to ACTH stimulation. Dogs with Δ-cortisol ≤ 83 nmol/L were 5.7 times as likely to be receiving vasopressors as were dogs with Δ-cortisol > 83 nmol/L. No differences were detected among dogs with sepsis, severe trauma, or GDV with respect to mean baseline and ACTH-stimulated serum cortisol concentrations, Δ-cortisol, and baseline plasma ACTH concentrations.

Conclusions and Clinical Relevance—Biochemical abnormalities of the hypothalamic-pituitary-adrenal axis indicative of adrenal gland or pituitary gland insufficiency were common in critically ill dogs, whereas exaggerated responses to ACTH administration were uncommon. Acutely ill dogs with Δ-cortisol ≤ 83 nmol/L may be more likely to require vasopressors as part of the treatment plan.

Restricted access
in Journal of the American Veterinary Medical Association