A 9.5-year-old 20.4-kg spayed female Border Collie was referred to the oncology service of Washington State University Veterinary Teaching Hospital for evaluation of a right anal gland mass and hypercalcemia. The referring veterinarian had evaluated the dog 3 weeks earlier for a 1- to 2-year history of alopecia, polydipsia, polyuria, and polyphagia; noticed a right anal gland mass; and then performed a CBC, serum biochemical analyses, serum thyroid and parathyroid panels, and abdominal ultrasonography. The CBC and thyroid panel results were within reference limits; however, the biochemical analyses revealed mildly high serum alanine aminotransferase (141 U/L; reference range, 18
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.
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.
Objective—To characterize the magnitude and duration of the antibody response against human albumin (HA) in critically ill and healthy dogs.
Design—Cohort and cross-sectional study.
Animals—Fourteen critically ill dogs that received 25% HA as part of their treatment protocol, 2 healthy dogs with no known previous exposure to HA that received 2 infusions of 25% HA (positive control dogs), and 47 healthy dogs and 21 critically ill dogs with no known exposure to HA (negative control dogs).
Procedures—An ELISA to detect IgG against HA was developed. Serum samples were obtained from the critically ill dogs prior to infusion of HA, at the time of hospital discharge, and 4 to 6 weeks and 6 months after HA administration. Serum samples were obtained at 2- to 4-week intervals from both positive control dogs for 101 weeks. A single serum sample was obtained from each of the negative control dogs.
Results—All 14 critically ill dogs developed serum IgG against HA. Peak antibody response was detected 4 to 6 weeks after HA administration. In both positive control dogs, IgG against HA was detected 10 days after HA administration and continued past 97 weeks. The peak antibody response was detected at 3 weeks in 1 dog and at 9 weeks in the other. Five of the 68 (7%) negative control dogs had a positive antibody response.
Conclusions and Clinical Relevance—Results suggested that dogs developed a pronounced IgG response following exposure to HA and that some dogs with no history of HA administration were positive for anti-HA IgG.
Objective—To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 μg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs.
Animals—10 clinically normal dogs.
Procedures—5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 μg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration.
Results—Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 μg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 μg of cosyntropin/kg. After administration of 0.5 and 1.0 μg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval.
Conclusions and Clinical Relevance—Administration of cosyntropin IV at a dose of 0.5 μg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.
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.
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.
Objective—To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV).
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.
Objective—To determine the lowest ACTH dose that would induce a maximum increase in serum cortisol concentration in healthy adult horses and identify the time to peak cortisol concentration.
Animals—8 healthy adult horses.
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) were administered IV (5 treatments/horse). Serum cortisol concentrations were measured before and 30, 60, 90, 120, 180, and 240 minutes after injection of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after injection.
Results—For all 4 doses, serum cortisol concentration was significantly increased, compared with the baseline value, by 30 minutes after administration of cosyntropin; no significant differences were detected among maximum serum cortisol concentrations obtained in response to administration of doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 30 minutes after administration of cosyntropin at a dose of 0.02 or 0.1 μg/kg, with peak concentrations 1.5 and 1.9 times, respectively, the baseline concentration. Serum cortisol concentration peaked 90 minutes after administration of cosyntropin at a dose of 0.25 or 0.5 μg/kg, with peak concentrations 2.0 and 2.3 times, respectively, the baseline concentration. Cosyntropin administration significantly affected WBC, neutrophil, and eosinophil counts and the neutrophil-to-lymphocyte ratio.
Conclusions and Clinical Relevance—Results suggested that in healthy horses, administration of cosyntropin at a dose of 0.1 μg/kg resulted in maximum adrenal stimulation, with peak cortisol concentration 30 minutes after cosyntropin administration.
Case Description—6 healthy dogs given human albumin solution as part of a study were examined following development of an immediate hypersensitivity reaction (1 dog) and signs suggestive of a type III hypersensitivity reaction (all 6 dogs).
Clinical Findings—All 6 dogs were healthy prior to administration of human albumin solution. One dog developed signs of an immediate hypersensitivity reaction, characterized by vomiting and facial edema, during administration of human albumin solution. All 6 dogs developed signs of a delayed adverse reaction 5 to 13 days after administration of human albumin solution. Initial clinical signs included lethargy, lameness, edema, cutaneous lesions indicative of vasculitis, vomiting, and inappetance.
Treatment and Outcome—In the dog with signs of immediate hypersensitivity, signs resolved after administration of human albumin solution was discontinued and diphenhydramine was administered. Supportive treatment was provided after dogs developed signs of a delayed adverse reaction. Four dogs recovered, but 2 dogs died despite treatment. All 6 dogs were found to have antihuman albumin antibodies. There was no evidence of contamination of the human albumin solution.
Clinical Relevance—Findings suggest that administration of human albumin solution in healthy dogs with normal serum albumin concentrations may result in signs of a type III hypersensitivity reaction.
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.