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Background: Increased serum cortisol (COR) concentrations may induce glucocorticoid resistance by down‐regulation of glucocorticoid receptor (GCR), resulting in decreased chemotherapy efficacy in dogs with lymphoma. Hypothesis: Investigate the relationship between serum COR concentrations and chemotherapy outcomes in dogs with lymphoma. Animals: Thirty client‐owned dogs with lymphoma, with serum COR concentration measured using serum samples collected at diagnosis. Methods: Retrospective study. Dogs were divided into 2 groups based on serum COR concentrations: a normal group (n = 16) with COR concentrations <6 μg/dL and a high group (14) with COR concentrations ≥6 μg/dL. We compared signalment, clinical signs, stage, type of lymphoma, adrenal gland size, alkaline phosphatase (ALP) activity, response to chemotherapy, progression‐free survival (PFS), overall survival (OS), and rate of P‐glycoprotein (P‐gp)‐ and GCR‐positive cells between the 2 groups. Results: No significant differences were found in the demographic characteristics between the 2 groups. However, the high COR group exhibited a significantly lower response to chemotherapy, PFS, and OS compared with the normal COR group. Serum ALP activity was significantly higher in the high COR group than in the normal COR group. Adrenal gland size was also significantly larger in the high COR group. Although no significant differences were found in the rate of P‐gp‐positive cells between the 2 groups, the rate of GCR‐positive cells was significantly lower in the high COR group. Conclusions and Clinical Importance: Our data suggests that measurement of serum COR concentrations may serve as a potential prognostic factor and evaluation index. [ABSTRACT FROM AUTHOR]

Background: Evidence indicating the optimal treatment protocol for dogs in adrenal crisis is lacking. Objectives: Compare outcomes of dogs presented in adrenal crisis treated with either hydrocortisone (HC) continuous rate infusion (CRI) or intermittent dexamethasone (DEX) administration. Animals: Thirty‐nine client‐owned dogs. Methods: Multi‐institutional retrospective observational study (July 2016‐May 2022) including dogs diagnosed with adrenal crisis and with available sequential blood work during hospitalization. Dogs were excluded if already on treatment with exogenous corticosteroids. Outcomes assessed included duration of hospitalization, survival, number of repeat measurements of electrolyte concentrations, and time to normalization of electrolyte and acid‐base status. Results: No significant difference was found between the groups for hospitalization time (P =.41; HC median [range] 48 h [19‐105 h]; DEX 57 h [17‐167 h]) nor case fatality rate 2/28 in the DEX group and 0/11 in the HC group (P = 1), nor in number of measurements of electrolyte concentrations (P =.90; HC 4 [2‐10]; DEX 4.5 [2‐15]). No significant differences were found between the 2 treatment groups in time to normalization of serum Na (P =.30; HC 33 h [7‐66 h]; DEX 16 h [1.5‐48 h]), K (P =.92; HC 17 h [4‐48 h]; DEX 16 h [1.25‐60 h]) or Na/K ratio (P =.08; HC 17 h [8‐48 h]; DEX 26 h [1.5‐60 h]). Conclusions: This study detected no difference in outcomes for dogs in adrenal crisis treated with either DEX boluses or HC CRIs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Resting cortisol concentrations are routinely measured in dogs with chronic gastrointestinal signs to rule out hypoadrenocorticism based on a concentration >2 μg/dL (>55 nmol/L). Hypothesis/Objectives: To assess the cross‐sectional prevalence of hypoadrenocorticism in a group of dogs with chronic gastrointestinal signs presented to a referral internal medicine service. Animals: Two‐hundred and eighty‐two client‐owned dogs with chronic gastrointestinal signs and with resting cortisol concentration testing performed. Methods: Retrospective review of medical records (final diagnosis, resting cortisol concentration, and adenocorticotropic hormone [ACTH] stimulation test results) of a referral population of dogs between May 2013 and September 2017. Results: Resting cortisol concentration was <2 μg/dL (<55 nmol/L) in 79 patients (28%). Repeated resting cortisol concentration measurements were performed in 28 dogs, and in 8, resting cortisol concentrations remained <2 μg/dL (<55 nmol/L). Post‐ACTH cortisol concentration was <2 μg/dL (<55 nmol/L) in 1 dog, consistent with a diagnosis of hypoadrenocorticism and giving a prevalence estimate of hypoadrenocorticism in this population of dogs of 0.3% (95% confidence interval [95CI], 0.03‐1.5%). In 19 dogs with an initial resting cortisol concentration <2 μg/dL (<55 nmol/L), hypoadrenocorticism was excluded based on a repeat resting cortisol concentration >2 μg/dL (>55 nmol/L). Overall, the most common diagnosis was chronic primary inflammatory enteropathy (176/282, 62.4%), followed by extragastrointestinal neoplasia (17/282, 6%), protein‐losing enteropathy, pancreatitis and megaesophagus (10/282, 3.5% each). Conclusions and Clinical Importance: Although dogs with hypoadrenocorticism can present with chronic gastrointestinal signs, it was the final diagnosis in only 1 of 282 dogs presenting to a referral internal medicine service for signs of chronic enteropathy. Repeated resting cortisol concentration may be considered as a test to try and exclude hypoadrenocorticism. [ABSTRACT FROM AUTHOR]

A 11‐year‐old male neutered Shih Tzu was referred to a tertiary facility with a history of weight loss, decreased appetite, polydipsia, and lethargy. The dog had a 10‐year history of nonspecific allergic dermatitis and was being treated with 16 mg/kg of ketoconazole q12h for Malassezia dermatitis. Vague gastrointestinal signs, hypocholesterolemia, and lack of a stress leukogram increased suspicion for hypoadrenocorticism (HA). An adrenocorticotropic hormone (ACTH) stimulation test identified hypocortisolemia on pre‐ and post‐ACTH samples and ketoconazole was discontinued. After a short course of corticosteroid treatment, an ACTH stimulation test was repeated and pre‐ACTH cortisol concentration was within the reference range, and the post‐ACTH cortisol concentration was mildly increased. The temporal association between return of adequate adrenocortical cortisol production and discontinuation of ketoconazole led to the conclusion that the dog had developed iatrogenic HA secondary to ketoconazole treatment. [ABSTRACT FROM AUTHOR]

Background The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. Hypothesis/Objectives To report the components of biological and analytical variability in serum cortisol concentration post- ACTH stimulation ([cortisol]) in healthy dogs. Animals Fourteen healthy harrier hound dogs. Methods The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate ( CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements ( C D), and the number of measurements required to assess the homeostatic set point ( HSP) of [cortisol] with confidence intervals ( CI) of 90 and 95% were estimated. Results The IoI was equal to 1.1 and the C D was 3.3 μg/ dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 μg/ dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 μg/ dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. Conclusions and Clinical Importance False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large C D emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC. [ABSTRACT FROM AUTHOR]

Background There are breed differences in several blood variables in healthy dogs. Objective Investigate breed variation in plasma endothelin-1 ( ET-1) concentration, plasma renin activity, and serum cortisol concentration. Animals Five-hundred and thirty-one healthy dogs of 9 breeds examined at 5 centers (2-4 breeds/center). Methods Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis. Results Median ET-1 concentration was 1.29 (interquartile range [ IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 ( IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 ( IQR, 0.48-1.10) ng/ mL/h in all dogs. Overall, breed differences were found in ET-1 and cortisol concentrations, and renin activity ( P < .0001 for all). Pair-wise comparisons between breeds differed in 67% of comparisons for ET-1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET-1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET-1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers. Conclusions and Clinical Importance Breed variation might be important to take into consideration when interpreting test results in clinical studies. [ABSTRACT FROM AUTHOR]

Background The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice. Objectives The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs. Animals Twenty-two healthy dogs, 10 dogs with suspected hypoadrenocorticism ( HA) and 15 dogs with suspected hyperadrenocorticism ( HC). Methods Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation. Results Peak cortisol concentrations were reached after 2-4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol-increase above the detection-limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours. Conclusions and Clinical Importance The depot formulation can be used in place of the short-acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA-suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time. [ABSTRACT FROM AUTHOR]