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- Author or Editor: Ellen N. Behrend x
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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.
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)
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.
Abstract
Objective—To validate a novel high-sensitivity radioimmunoassay (RIA) procedure developed to accurately measure the relatively low serum total thyroxine (T4) concentrations of birds and reptiles and to establish initial reference ranges for T4 concentration in selected species of psittacine birds and snakes.
Animals—56 healthy nonmolting adult psittacine birds representing 6 species and 42 captive snakes representing 4 species.
Procedure—A solid-phase RIA designed to measure free T4 concentrations in dialysates of human serum samples was used without dialysis to evaluate total T4 concentration in treated samples obtained from birds and reptiles. Serum T4 binding components were removed to allow assay of undialyzed samples. Assay validation was assessed by determining recovery of expected amounts of T4 in treated samples that were serially diluted or to which T4 was added. Intra- and interassay coefficient of variation (CV) was determined.
Results—Mean recovery of T4 added at 4 concentrations ranged from 84.9 to 115.0% and 95.8 to 119.4% in snakes and birds, respectively. Intra- and interassay CV was 3.8 and 11.3%, respectively. Serum total T4 concentrations for 5 species of birds ranged from 2.02 to 7.68 nmol/L but ranged from 3.17 to 142 nmol/L for blue-fronted Amazon parrots; concentrations ranged from 0.21 to 6.06 nmol/L for the 4 species of snakes.
Conclusions and Clinical Relevance—This new RIA method provides a commercially available, accurate, and sensitive method for measurement of the relatively low serum T4 concentrations of birds and snakes. Initial ranges for the species evaluated were established. (Am J Vet Res 2001;62:1750–1767)
Abstract
OBJECTIVE
To evaluate effects of the addition of glucose to dog and cat urine on urine specific gravity (USG) and determine whether glucosuria affects assessment of renal concentrating ability.
SAMPLE
Urine samples from 102 dogs and 59 cats.
PROCEDURES
Urine for each species was pooled to create samples with various USGs. Glucose was added to an aliquot of each USG pool (final concentration, 2,400 mg/dL), and serial dilutions of the glucose-containing aliquot were created for each pool. The USG then was measured in all samples. The difference in USG attributable to addition of glucose was calculated by subtracting the USG of the unaltered sample from the USG of the sample after the addition of glucose. The relationship between the difference in USG and the USG of the unaltered, undiluted sample was evaluated by the use of linear regression analysis.
RESULTS
Addition of glucose to urine samples increased the USG. There was a significant relationship between USG of the undiluted sample and the difference in USG when glucose was added to obtain concentrations of 300, 600, 1,200, and 2,400 mg/dL in canine urine and concentrations of 600, 1,200, and 2,400 mg/dL in feline urine. The more concentrated the urine before the addition of glucose, the less change there was in the USG. Changes in USG attributable to addition of glucose were not clinically important.
CONCLUSIONS AND CLINICAL RELEVANCE
Substantial glucosuria resulted in minimal alterations in specific gravity of canine and feline urine samples. Thus, USG can be used to assess renal concentrating ability even in samples with glucosuria.
Abstract
Objective—To assess serum 17-α-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism.
Design—Prospective study.
Animals—16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism.
Procedure—ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia.
Results—In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated.
Conclusions and Clinical Relevance—Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration. (J Am Vet Med Assoc 2005;227:1762–1767)
Abstract
Objective—To evaluate responses of cats with vaccine- associated sarcomas to treatment with surgery and radiotherapy, with or without adjunctive chemotherapy.
Design—Retrospective study.
Animals—76 cats (78 tumors).
Procedure—Medical records were reviewed. Factors potentially associated with survival time, time to recurrence, and time to development of metastases were evaluated.
Results—Following excision, electron beam radiation, and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time.
Conclusions and Clinical Relevance—Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine- associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate. (J Am Vet Med Assoc 2001;219:1582–1589)
Abstract
Objective—To determine the lowest ACTH dose that would induce a significant increase in serum cortisol concentration and identify the time to peak cortisol concentration in healthy neonatal foals.
Design—Prospective randomized crossover study.
Animals—11 healthy neonatal foals.
Procedures—Saline (0.9% NaCl) solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 μg/kg [0.009, 0.045, 0.114, and 0.227 μg/lb]) of cosyntropin (synthetic ACTH) was administered IV. Serum cortisol concentrations were measured before and 10, 20, 30, 60, 90, 120, 180, and 240 minutes after administration of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after administration.
Results—Serum cortisol concentration was significantly increased, compared with baseline, by 10 minutes after cosyntropin administration at doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 20 minutes after administration of cosyntropin at doses of 0.02, 0.1, and 0.25 μg/kg, with peak concentrations 1.7, 2.0, and 1.9 times the baseline concentration, respectively. Serum cortisol concentration peaked 30 minutes after cosyntropin administration at a dose of 0.5 μg/kg, with peak concentration 2.2 times the baseline concentration. No significant differences were detected among peak serum cortisol concentrations obtained with cosyntropin administration at doses of 0.25 and 0.5 μg/kg. Cosyntropin administration significantly affected the lymphocyte count and the neutrophil-to-lymphocyte ratio.
Conclusions and Clinical Relevance—Results suggested that in healthy neonatal foals, the lowest dose of cosyntropin to result in significant adrenal gland stimulation was 0.25 μg/kg, with peak cortisol concentration 20 minutes after cosyntropin administration.
Abstract
Objective—To determine the lowest dose of cosyntropin on a per body weight basis that would produce maximal cortisol and aldosterone secretion and the ideal timing of blood sample collection after ACTH stimulation in healthy cats.
Design—Randomized crossover trial.
Animals—7 adult sexually intact male purpose-bred cats.
Procedures—Each cat received saline (0.9% NaCl) solution (control) and 5 doses (125 μg/cat and 10, 5, 2.5, and 1 μg/kg [4.54, 2.27, 1.14, and 0.45 μg/lb]) of cosyntropin IV with a 2-week washout period between treatments. Blood samples were obtained before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after administration of saline solution or cosyntropin.
Results—Serum cortisol and aldosterone concentration increased significantly, compared with baseline values, after administration of all cosyntropin doses. Lower doses of cosyntropin resulted in an adrenocortical response equivalent to the traditional dose of 125 μg/cat. The lowest doses of cosyntropin that stimulated a maximal cortisol and aldosterone response were 5 and 2.5 μg/kg, respectively. Lower doses of cosyntropin resulted in a shorter interval between IV administration of cosyntropin and peak serum cortisol and aldosterone concentrations.
Conclusions and Clinical Relevance—Low-dose ACTH stimulation testing with IV administration of cosyntropin at 5 μg/kg followed by blood sample collection at 60 to 75 minutes resulted in concurrent peak serum cortisol and aldosterone concentrations that were equivalent to those achieved following administration of cosyntropin at 125 μg/cat, the standard dose currently used.
Abstract
Objective—To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%.
Sample—24 adrenal glands from 18 mixed-breed dogs.
Procedures—Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability.
Results—Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively.
Conclusions and Clinical Relevance—Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.
