Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is effective as a stand-alone therapy for feline diabetes mellitus: the SENSATION study.

OBJECTIVE: To investigate safety and effectiveness of velagliflozin oral solution as sole therapy in naïve and previously insulin-treated diabetic cats. ANIMALS: 252 client-owned cats receiving ≥ 2 doses of velagliflozin; 214 (85%) naïve diabetics and 38 (15%) insulin-treated diabetics. PROCEDURES: Prospective, baseline-controlled, open-label clinical field trial. Cats received velagliflozin orally, once daily. Physical examinations and blood collections were performed days 0, 3, 7, 30, 60, 120, and 180. RESULTS: Data are median (range). Screening blood glucose (BG) was 436 mg/dL (272 to 676 mg/dL). On days 30, 60, 120, and 180, single BG after receiving velagliflozin was 153 mg/dL (62 to 480 mg/dL), 134 mg/dL (64 to 414 mg/dL), 128 mg/dL (55 to 461 mg/dL), and 125 mg/dL (77 to 384 mg/dL), respectively. Screening fructosamine was 538 µmol/L (375 to 794 µmol/L). On the same recheck days, fructosamine was 310 µmol/L (204 to 609 µmol/L), 286 µmol/L (175 to 531 µmol/L), 269 µmol/L (189 to 575 µmol/L), and 263 µmol/L (203 to 620 µmol/L). At day 180, 81% of 158 cats remaining had BG and/or fructosamine within reference ranges; 88.6% (124 of 140) and 87.7% (121 of 138) showed improvement in polyuria and polydipsia, respectively. Ketonuria developed in 35 cats (13.9%), including 18 (7.1%) that had ketoacidosis. Ketoacidosis was less common in naïve diabetic cats (11 of 214 [5.1%]) compared to insulin-treated diabetic cats (7 of 38 [18.4%]). At ketoacidosis diagnosis, 14 of 18 cats (77.8%) were euglycemic (ie, BG < 250 mg/dL). Most episodes of ketosis or ketoacidosis (30 of 35 [85.7%]) occurred within the first 14 days of treatment. Insulin-treated diabetic cats were less likely to complete the trial. No clinical hypoglycemia occurred. CLINICAL RELEVANCE: Velagliflozin improved glycemic parameters and clinical signs in diabetic cats. Velagliflozin provides an alternative to insulin as a stand-alone treatment of diabetic cats.

The impact of single-dose trazodone administration on plasma endogenous adrenocorticotropic hormone and serum cortisol concentrations in healthy dogs.

BACKGROUND: Conditions affecting the hypothalamic-pituitary-adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha-1 adrenergic activity. OBJECTIVES: Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. ANIMALS: Fourteen healthy, adult, companion dogs. METHODS: Prospective, randomized placebo-controlled study. Trazodone (8-10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7-day wash-out period, dogs received the opposite treatment. Differences in eACTH, pre- and post-ACTH stimulation cortisol concentrations, and delta (difference between pre- and post-ACTH) cortisol concentrations were analyzed using a paired t or signed-rank test with a P < .05 significance level. RESULTS: The eACTH concentrations were not significantly different (P = .23) between treatments. Similarly, no significant differences were found in the pre-ACTH cortisol concentrations between treatments (P = .40). Post-ACTH cortisol concentrations (P = .05) and delta cortisol concentrations (P = .04) were significantly lower when the dogs were treated with trazodone. CONCLUSIONS: Preliminary data suggest trazodone administration dampens the adrenocortical response to stimulation in healthy dogs. If similar effects are found in dogs with adrenal disease, the use of trazodone may affect diagnosis and clinical decision making in these populations.

Impact on result interpretation of correct and incorrect selection of veterinary glucometer canine and feline settings.

Veterinary glucometers should be correctly coded for the patient species; however, coding errors occur in clinical settings and the impact of such errors has not been characterized. We compared glucose concentrations in 127 canine and 37 feline samples using both canine and feline settings on a veterinary glucometer (AlphaTrak; Zoetis). All samples were measured first on the canine setting and then measured using the feline setting. Glucose concentration was also measured using a central laboratory biochemical analyzer (Cobas c311; Roche). Three data comparisons for each species were investigated: incorrectly coded glucometer vs. correctly coded glucometer, correctly coded glucometer vs. Cobas c311, and incorrectly coded glucometer vs. Cobas c311. For each comparison, the following analyses were conducted: Spearman rank correlation coefficient, Bland-Altman difference plot analysis, mountain plot analysis, and Deming regression. For clinical context, Clarke error grids were constructed. There was high positive correlation for all comparisons with both species. For all comparisons, mean difference was low (-0.7 to 0.5 mmol/L for canine samples, 1.0-2.0 mmol/L for feline samples). Incorrect glucometer coding resulted in proportional bias for canine samples and positive constant bias for feline samples, and individual differences could be large (-4.44 mmol/L for one dog, 6.16 mmol/L for one cat). Although the glucometer should be used per the manufacturer's recommendation, coding errors are unlikely to have severe adverse clinical consequences for most patients based on error grid analysis.

Comparison of glucose concentrations in canine whole blood, plasma, and serum measured with a veterinary point-of-care glucometer.

Previous studies have determined that, compared to whole blood, serum or plasma used in a portable blood glucometer (PBG) may provide more accurate results. We investigated the accuracy of a veterinary PBG (AlphaTRAK 2; Zoetis) for the measurement of glucose concentrations in serum, plasma, and whole blood compared to plasma glucose concentration measured by a biochemical analyzer. Blood samples from 53 client-owned dogs were collected. Lin concordance correlation coefficient (ρc) and Bland-Altman plots were used to determine correlation and agreement between the results obtained for the different sample types. Glucose concentration in whole blood measured by the veterinary PBG was more strongly correlated with the glucose concentration measured by the biochemical analyzer (ρc = 0.92) compared to plasma and serum glucose concentrations (ρc = 0.59 and 0.57, respectively). The mean differences between the glucose concentrations in whole blood, plasma, and serum measured by the veterinary PBG and the glucose concentration determined by the biochemical analyzer were 1.0, 6.3, and 6.7 mmol/L (18, 113, and 121 mg/dL), respectively. Our findings suggest that, when using this veterinary PBG, the accuracy of a glucose measurement obtained is higher when using whole blood compared to plasma or serum. Use of whole blood allows for more correct assessment and diagnosis, which are necessary for appropriate therapeutic intervention.

Accuracy of urine dipstick tests and urine glucose-to-creatinine ratios for assessment of glucosuria in dogs and cats.

OBJECTIVE: To assess the accuracy of automated readings of urine dipstick results for assessment of glucosuria in dogs and cats, compare visual versus automated readings of urine glucose concentration, and determine the utility of the urine glucose-to-creatinine ratio (UGCR) for quantification of glucosuria. SAMPLE: 310 canine and 279 feline urine samples. PROCEDURES: Glucose concentration was estimated in 271 canine and 254 feline urine samples by visual assessment of urine dipstick results and with an automated dipstick reader. Absolute urine glucose and creatinine concentrations were measured in 39 canine and 25 feline urine samples by colorimetric assay with a clinical chemistry analyzer (reference standard for detection of glucosuria), and UGCRs were determined. RESULTS: Automated assessment of the urine dipsticks yielded accurate results for 163 (60.1%) canine urine samples and 234 (92.1%) feline urine samples. Sensitivity of the automated dipstick reader for detection of glucosuria was 23% for canine samples and 68% for feline samples; specificity was 99% and 98%, respectively. Visual readings were more accurate than automated readings for both canine and feline urine. The UGCR was significantly correlated with absolute urine glucose concentration for both dogs and cats, yet there was incomplete distinction between dipstick categories for glucose concentration and UGCR. CONCLUSIONS AND CLINICAL RELEVANCE: Urine dipstick readings for dogs and cats were useful for ruling glucosuria in when the result was positive but not for ruling it out when the result was negative. The evaluated dipsticks were more accurate for detection of glucosuria in cats than in dogs. Visual dipstick readings were more accurate than automated readings. The UGCR did not appear to provide additional useful information.

Effect of EDTA on measurement of cortisol and thyroxine by chemiluminescent enzyme immunoassay in dogs.

The addition of ethylenediamine tetra-acetic acid (EDTA) to serum can affect the measurement of cortisol by chemiluminescent enzyme immunoassay (CEIA); addition of magnesium chloride (MgCl2) may reverse the effects. However, similar characteristics for thyroxine (T4) measurement are unknown. We measured cortisol and T4 in paired EDTA-anticoagulated plasma and serum samples from 50 dogs. Additionally, both hormones were measured in 15 samples of each type after the addition of MgCl2. Samples were collected under routine clinical conditions; therefore, specific EDTA concentrations in plasma samples were unknown. Cortisol and T4 values were significantly different comparing plasma and serum samples in the absence of MgCl2. For cortisol and T4, EDTA-plasma concentrations were 51.2% and 43.7% higher than serum, respectively (p < 0.001 for both). The addition of MgCl2 to plasma significantly decreased the measured cortisol concentrations (p < 0.001) but not T4 (p = 0.44). After addition of MgCl2, cortisol concentrations in EDTA-plasma were no longer significantly different from serum, whereas T4 concentrations in EDTA-plasma remained significantly different from serum. In the clinical setting in which tubes may be underfilled, use of EDTA-plasma significantly increases the measured concentration of cortisol and T4 obtained by CEIA. Addition of MgCl2 to EDTA-plasma can overcome the effects of EDTA when measuring cortisol, but not T4. Thus, T4 should not be measured in EDTA-plasma.

Effect on urine specific gravity of the addition of glucose to urine samples of dogs and cats.

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.

Serum theophylline after multiple dosing with transdermal gels in cats.

OBJECTIVES: Our objectives were, first, to determine if therapeutic serum theophylline concentrations could be achieved using long-term, once-daily dosing of transdermal theophylline and, secondarily, to evaluate the difference between two transdermal theophylline formulations. METHODS: Seven healthy cats, 1-10 years of age, were evaluated in a two-way, randomized, double-blinded, crossover study. Participants received transdermal theophylline at 15 mg/kg for 21 days in either pluronic lecithin organogel (PLO) or Lipoderm formulation. On day 22, blood was collected 2, 6, 14 and 24 h after dosing. After a 14 day washout period, blood was collected to verify non-detectible theophylline concentrations. The alternate formulation was administered for 21 days, and sampling was repeated. Serum theophylline concentrations were determined using an automated immunoassay. Serum concentrations were compared between formulations using a two-way random-measures ANOVA and over time within a formulation using a repeated-measures ANOVA. RESULTS: Therapeutic serum theophylline concentrations were achieved for 2/7 cats in each group. Of 56 serum theophylline measurements obtained, only seven (13%) were within the therapeutic range. No significant difference was detected in drug concentrations achieved by the transdermal formulations at any time point. In addition, no significant difference in serum theophylline concentrations was noted between time points for PLO ( P = 0.751) or Lipoderm ( P = 0.107). CONCLUSIONS AND RELEVANCE: Once-daily transdermal dosing of theophylline does not reliably achieve therapeutic concentrations. Individual cats may achieve therapeutic concentrations. No significant difference was noted between PLO and Lipoderm formulations. Therefore, transdermal theophylline formulations should not be considered as a first-line therapy in feline asthma patients.

Low-dose ACTH stimulation testing in dogs suspected of hypoadrenocorticism.

BACKGROUND: Low-dose ACTH stimulation testing would lower cost and may increase sensitivity for identification of partial ACTH deficiency. HYPOTHESIS: (1) The low-dose ACTH stimulation test will provide comparable results to the standard-dose ACTH stimulation test in dogs suspected of hypoadrenocorticism and (2) partial ACTH deficiency exists in dogs and can result in chronic, intermittent gastrointestinal signs. ANIMALS: Thirty-one client-owned dogs suspected of having hypoadrenocorticism. METHODS: Prospective study. Dogs suspected of having hypoadrenocorticism received 1 µg/kg cosyntropin IV for the first ACTH stimulation test; the second test was performed 4 h later and dogs received 5 µg/kg cosyntropin IV. Blood samples were obtained pre-ACTH and 1 hour post-ACTH for each dose (4 measurements total). Samples for endogenous ACTH measurement were obtained at the time of initial blood collection. RESULTS: No significant difference was observed in the basal cortisol concentration before administration of a 1 µg/kg versus before a 5 µg/kg dose of cosyntropin (P = .544). For dogs suspected of having hypoadrenocorticism, the ACTH-stimulated cortisol concentrations in response to both doses of ACTH were equivalent (90% confidence interval [CI], 80.5-97.2%; P = .04). No cases with partial ACTH deficiency were identified conclusively. CONCLUSIONS AND CLINICAL IMPORTANCE: A 1 µg/kg dose of cosyntropin is equivalent to a 5 µg/kg dose of cosyntropin for screening dogs suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was not identified in this small group of dogs.

Effect of blood contamination on results of dipstick evaluation and urine protein-to-urine creatinine ratio for urine samples from dogs and cats.

OBJECTIVE To evaluate effects of blood contamination on dipstick results, specific gravity (SG), and urine protein-to-urine creatinine ratio (UPCR) for urine samples from dogs and cats. SAMPLE Urine samples collected from 279 dogs and 120 cats. PROCEDURES Urine pools were made for each species (dogs [n = 60] and cats [30]). Blood was added to an aliquot of a pool, and serial dilutions were prepared with the remaining urine. Color and dipstick variables were recorded, and SG and UPCR were measured. For cats, 1 set of pools was used; for dogs, 2 sets were used. Comparisons were made between undiluted urine and spiked urine samples for individual colors. Repeated-measures ANOVA on ranks was used to compare dipstick scores and UPCR results; χ2 tests were used to compare proteinuria categorizations (nonproteinuric, borderline, or proteinuric). RESULTS Any blood in the urine resulted in significantly increased dipstick scores for blood. In both species, scores for bilirubin and ketones, pH, and SG were affected by visible blood contamination. No significant difference for the dipstick protein reagent results was evident until a sample was visibly hematuric. The UPCR was significantly increased in dark yellow samples of both species. Proteinuria categorizations differed significantly between undiluted urine and urine of all colors, except light yellow. CONCLUSIONS AND CLINICAL RELEVANCE Any degree of blood contamination affected results of dipstick analysis. Effects depended on urine color and the variable measured. Microscopic blood contamination may affect the UPCR; thus, blood contamination may be a differential diagnosis for proteinuria in yellow urine samples.

Excess EDTA interferes with cortisol measurement using a solid-phase, chemiluminescent enzyme immunoassay.

Hormone assays that use a solid-phase, automated, chemiluminescent enzyme immunoassay (CEIA) with an alkaline phosphatase-tagged hormone or antibody as a reporter are performed on serum or EDTA plasma in our laboratory. CEIA cortisol results appeared to increase in the presence of excess EDTA. We investigated the effect of the addition of different amounts of EDTA on cortisol concentrations in pooled canine serum samples. The recommended EDTA plasma concentration of 4.1 mmol/L (1.8 mg/mL) did not alter cortisol concentrations when added to serum pools; however, the addition of ≥5.1 mmol/L (2.25 mg/mL) of EDTA increased apparent concentrations of cortisol. Supplementation of serum samples with MgCl2 to 5 mmol/L reversed the effect of EDTA up to a concentration of ~8.1 mmol/L (3.6 mg/mL). Our findings show that CEIA cortisol results on EDTA plasma can be artificially increased if the EDTA concentration exceeds 5.1 mmol/L.

Effect of laparotomy on the pituitary-adrenal axis in dogs.

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.

Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs.

Serum aldosterone and cortisol concentrations before and after suppression with fludrocortisone in cats: a pilot study.

Primary hyperaldosteronism is an increasingly recognized syndrome in cats, and diagnosis can be difficult. A potential diagnostic method has been reported, utilizing oral fludrocortisone administered twice daily for 4 days followed by collection of urine. In the current study, we sought to determine if blood sampling and a shorter dosing period would provide a possible means to test for primary hyperaldosteronism. Also, cortisol concentrations were measured to assess the potential of fludrocortisone to act as a glucocorticoid in cats. In phase I, 8 healthy laboratory cats were studied in a placebo-controlled, crossover design. Serum aldosterone and cortisol concentrations were measured before and on the second, third, and fourth day of treatment and compared within groups. In phase II, based on the results obtained in phase I, 8 healthy client-owned cats were administered 3 doses of fludrocortisone or placebo. Serum aldosterone and cortisol concentrations were compared before and after treatment within groups. In both phases, serum aldosterone and cortisol concentrations were significantly suppressed in fludrocortisone-treated cats. Thus, it was determined that oral administration of fludrocortisone causes suppression of serum aldosterone in healthy adult cats after only 3 doses. Further research is needed to determine the effects of oral fludrocortisone in cats with primary hyperaldosteronism and cats with other disorders causing hypertension and/or hypokalemia to determine if this protocol can be used as a tool for the definitive diagnosis of primary hyperaldosteronism.

Ultrasonographic evaluation of adrenal gland size compared to body weight in normal dogs.

The accepted cut-off value for adrenal gland maximum diameter of 0.74 cm to distinguish adrenal gland enlargement in dogs regardless of body weight may not be appropriate for small to medium breed dogs. The purpose of the current retrospective study was to examine adrenal gland dimensions as a function of body weight in healthy dogs in three weight categories (< 10 kg, 10-30 kg, and > 30 kg) representing small, medium, and large breeds, respectively, to establish greater confidence in determining if adrenal gland size is abnormal. The measurements of length (sagittal plane), cranial and caudal pole thickness (sagittal and transverse planes), and caudal pole width (transverse plane) of both adrenal glands were obtained ultrasonographically in clinically healthy dogs (n = 45) with 15 dogs in each weight group. Findings support our hypothesis that adrenal gland size correlates with body weight in normal dogs, and more precise reference intervals should be created for adrenal gland size by categorizing dogs as small, medium, or large breed. The caudal pole thickness of either adrenal gland in a sagittal plane was the best dimension for evaluating adrenal gland size based on low variability, ease, and reliability in measurement.

Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia.

The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.

Validation of a low-dose adrenocorticotropic hormone stimulation test in healthy neonatal foals.

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.

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia.

PURPOSE: The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock. METHODS: Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80-90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose. RESULTS: Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05-9.11; p = 0.04). CONCLUSIONS: Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.

Adrenocortical carcinoma in a dog with incomplete excision managed long-term with metastasectomy alone.

A 10 yr old bichon frise presented with a 3 mo history of polyuria, polydipsia, and hind limb weakness. Serum biochemistry revealed persistent hypokalemia. A left adrenal gland mass with right adrenal atrophy was detected ultrasonographically. Basal serum cortisol concentration was at the low end of normal (30 nmol/L; reference range, 30-140 nmol/L) and adrenocorticotropic hormone (ACTH)-stimulated cortisol concentration was low (199 nmol/L; reference range, 220-470 nmol/L). Basal serum 17-α-OH progesterone concentration was also low (0.03 ng/mL; reference range, 0.06-0.30 ng/mL), but the aldosterone concentration 2 hr after the ACTH stimulation was elevated (> 3,000 pmol/L; reference range, 197-2,103 pmol/L). A left adrenalectomy and nephrectomy were performed. Histopathology revealed an adrenocortical zona glomerulosa carcinoma. Surgical excision was considered incomplete; however, clinical signs resolved. Two years later, basal and ACTH-stimulated aldosterone concentrations were elevated. Computed tomography demonstrated a mass effect in the liver. The left lateral and left medial hepatic lobes were removed. Histopathology confirmed metastatic endocrine carcinoma. The patient was stable 1,353 days postsurgically (when this report was prepared). This is the first case report of a metastatic adrenal carcinoma that was successfully managed surgically for > 3 yr.

Seasonal variation in results of diagnostic tests for pituitary pars intermedia dysfunction in older, clinically normal geldings.

OBJECTIVE: To determine whether seasonal variations exist in endogenous plasma ACTH, plasma α-melanocyte-stimulating hormone (α-MSH), serum cortisol, and serum insulin concentrations and in the results of a dexamethasone suppression test for older, clinically normal geldings in Alabama. DESIGN: Cohort study. ANIMALS: 15 healthy mixed-breed geldings (median age, 14 years). PROCEDURES: Sample collection was repeated monthly for 12 months. Dexamethasone (0.04 mg/kg [0.02 mg/lb], IM) was administered and cortisol concentrations were determined at 15 and 19 hours. Radioimmunoassays were used to measure ACTH, α-MSH, cortisol, and insulin concentrations at each testing time. Hormone concentrations were compared between months via repeated-measures ANOVA and correlated with age within each month. RESULTS: A significant time effect was found between months for α-MSH and insulin concentrations. Endogenous cortisol and ACTH concentrations remained within existing reference ranges. Significant correlations were detected between age and ACTH concentration for several fall and winter months and between age and insulin concentration for September. CONCLUSIONS AND CLINICAL RELEVANCE: Older horses have higher ACTH concentrations in several fall and winter months and higher insulin concentrations in September than do younger horses. Seasonally specific reference ranges are required for α-MSH and insulin concentrations, with significantly higher concentrations detected in the fall. Practitioners should be advised to submit samples only to local laboratories that can provide such reference ranges for their local geographic region.