Use of the Cortisol‐to‐ACTH Ratio for Diagnosis of Primary Hypoadrenocorticism in Dogs

Background

The ACTH stimulation test is currently required for definitive diagnosis of hypoadrenocorticism. Increased cost of synthetic ACTH (cosyntropin) has prompted a search for alternative diagnostic methods.

Objective

The purpose of this study was to determine whether a cortisol‐to‐ACTH ratio (CAR) can be used to differentiate dogs with hypoadrenocorticism from normal dogs and those with nonadrenal illness.

Animals

Eight healthy dogs (H), 19 dogs with nonadrenal illness (NAI), and 15 dogs with hypoadrenocorticism (HAD).

Methods

Dogs in the HAD group were retrospectively identified from PUVTH medical records. The NAI group consisted of hospitalized dogs with clinical signs, clinicopathologic findings, or both, consistent with a diagnosis of hypoadrenocorticism, but in which hypoadrenocorticism was ruled out based on ACTH stimulation test results. Healthy dogs were recruited from hospital staff and students. Endogenous ACTH concentrations and cortisol concentrations before and after ACTH stimulation were measured in all dogs.

Results

Baseline cortisol concentration was significantly lower, and ACTH concentration was significantly higher, in the HAD group versus the H and NAI group (P < .001). However, there was overlap among groups. Cortisol‐to‐ACTH ratio was significantly lower in the HAD group versus the H and NAI groups (P < .001), and there was no overlap between the HAD group and the other 2 groups.

Conclusions and Clinical Importance

CAR can be used for definitive diagnosis of primary hypoadrenocorticism.     

Effect of Trilostane and Mitotane on Aldosterone Secretory Reserve in Dogs with Pituitary‐Dependent Hyperadrenocorticism

Background

Maximal aldosterone secretion in healthy dogs occurs 30 minutes postadrenocorticotropin (ACTH; 5 μg/kg IV) stimulation. The effect of trilostane and mitotane on aldosterone at that time is unknown.

Objectives

To assess the effect of trilostane and mitotane in dogs with pituitary‐dependent hyperadrenocorticism on aldosterone secretory reserve. To determine if aldosterone concentration correlates with electrolyte concentrations.

Animals

Serum collected from 79 client‐owned dogs and 33 stored samples.

Methods

Client‐owned dogs had ACTH stimulation tests with cortisol concentrations measured at 0 and 60 minutes and aldosterone concentrations measured at 0, 30, and 60 minutes. Stored samples had aldosterone concentrations measured at 0 and 60 minutes. Ten historical clinically healthy controls were included. All had basal sodium and potassium concentrations measured.

Results

The aldosterone concentrations in the mitotane‐ and trilostane‐treated dogs at 30 and 60 minutes post‐ACTH were significantly lower than in clinically healthy dogs; no significant difference was detected in aldosterone concentration between 30 and 60 minutes in treated dogs. However, a significantly higher percentage of dogs had decreased aldosterone secretory reserve detected at 30 minutes than at 60 minutes. At 30 minutes, decreased secretory reserve was detected in 49% and 78% of trilostane‐ and mitotane‐treated dogs, respectively. No correlation was detected between aldosterone and serum electrolyte concentrations.

Conclusions and Clinical Importance

Decreased aldosterone secretory reserve is common in trilostane‐ and mitotane‐treated dogs; it cannot be predicted by measurement of serum electrolyte concentrations. Aldosterone concentration at 30 minutes post‐ACTH stimulation identifies more dogs with decreased aldosterone secretory reserve than conventional testing at 60 minutes.     

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH

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.     

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Background

An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.

Objectives

To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).

Animals

Thirty healthy dogs and 15 client‐owned dogs with PDH.

Methods

Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.

Results

The serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.

Conclusions and Clinical Importance

Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.     

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

Iron Status in Blood Donor Dogs

Background

Despite the popularity of canine blood donor (BD) programs, there is scarce scientific information regarding iron status in this canine population of dogs.

Objective

To assess iron status in dogs used in a blood donor program.

Animals

A total of 130 healthy dogs (75 BD, 55 controls [C]) were included. A subset of dogs (n = 12) were used to evaluate the effects of repetitive donations by having a second and more recent sample analyzed.

Methods

Serum iron concentration (SI), unsaturated iron‐binding capacity (UIBC), total iron‐binding capacity (TIBC), and percentage transferrin saturation (%SAT) were obtained. Values were compared using a 2‐way ANOVA (factors: BD status, breed). For the subset of BD, the first sample (less frequent donors ‐LD‐, after a mean of 3.8 donations) was compared to a second sample (experienced donors ‐ED‐, mean 13.6 donations) using a paired t‐test.

Results

SI (183.7 ± 55.3 μg/dL) and %SAT (55.7 ± 17.4%) were higher and UIBC (152.6 ± 73.3 μg/dL) was lower in BD dogs than in C (153.9 ± 51.7 μg/dL, 43.8 ± 17.8%, and 224.1 ± 120.6 μg/dL, respectively). Also, UIBC and TIBC were lower, and %SAT higher in Greyhounds when compared with non‐Greyhounds. ED had decreased %SAT and increased UIBC and TIBC when compared with LD.

Conclusions and Clinical Importance

Our canine BD population did not have iron deficiency and had higher SI concentration than C. However, ED (~14 consecutive blood donations every ~8 weeks) developed a mild iron deficiency, although values were still within canine reference intervals. Greyhounds have higher %SAT than non‐Greyhounds, which might be a breed‐specific peculiarity.     

Relation of Vitamin D Status to Congestive Heart Failure and Cardiovascular Events in Dogs

Background

Vitamin D plays a pivotal role in cardiac function, and there is increasing evidence that vitamin D deficiency is associated with the development of congestive heart failure (CHF) in people.

Hypothesis

Serum vitamin D concentration is lower in dogs with CHF compared with unaffected controls and serum vitamin D concentration is associated with clinical outcome in dogs with CHF.

Animals

Eighty‐two client‐owned dogs.

Methods

In this cross‐sectional study, we examined the association between circulating 25‐hydroxyvitamin D [25(OH)D], a measure of vitamin D status, and CHF in dogs. In the prospective cohort study, we examined whether 25(OH)D serum concentration was associated with clinical outcome in dogs with CHF.

Results

Mean 25(OH)D concentration (100 ± 44 nmol/L) in 31 dogs with CHF was significantly lower than that of 51 unaffected dogs (123 ± 42 nmol/L; P = .023). The mean calculated vitamin D intake per kg of metabolic body weight in dogs with CHF was no different from that of unaffected dogs (1.37 ± 0.90 μg/kg metabolic body weight versus 0.98 ± 0.59 μg/kg body weight, respectively, P = .097). There was a significant association of serum 25(OH)D concentration on time to clinical manifestation of CHF or sudden death (P = .02).

Conclusion and Clinical Relevance

These findings suggest that low concentrations of 25(OH)D may be a risk factor for CHF in dogs. Low serum 25(OH)D concentration was associated with poor outcome in dogs with CHF. Strategies to improve vitamin D status in some dogs with CHF may prove beneficial without causing toxicity.     

Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

Simpson's Method of Discs for Measurement of Echocardiographic End‐Diastolic and End‐Systolic Left Ventricular Volumes: Breed‐Specific Reference Ranges in Boxer Dogs

Background

Boxer dogs are predisposed to congenital and adult onset cardiac diseases. Breed‐specific reference values for M‐mode and Doppler echocardiographic measurements previously have been established. Left ventricular (LV) end‐systolic (ESV) and end‐diastolic volumes (EDV) can be measured by M‐mode or two‐dimensional methods, such as Simpson''s method of discs (SMOD). Reference ranges for SMOD‐derived LV volumes are lacking.

Objectives

To determine reference intervals for EDV and ESV in Boxer dogs.

Animals

Previously collected data from 85 healthy Boxers (37 males and 48 females) were used for analysis.

Methods

Simpson''s method of discs‐derived EDV and ESV were measured using offline analysis by 1 observer, in both the right parasternal and the left apical views. Measurements were compared between both views and between male and female dogs using a t‐test. Reference intervals were established using the mean + 2 × SD.

Results

Measurements obtained from both views showed good agreement, and mean EDVI and ESVI, indexed to body surface area (BSA), were calculated. Reference intervals were 49–93 mL/m² for EDVI, and 22–50 mL/m² for ESVI. EDV and ESV were significantly higher in males compared with females, when indexing to BSA, but not when indexing to body weight.

Conclusion and Clinical Importance

The upper limit for ESVI exceeds the previously suggested cut‐off of 30 mL/m² for detection of systolic dysfunction. The reference intervals generated in this study should be useful clinically in the assessment of LV size and function in Boxer dogs.     

Comparison of Adrenocorticotropic Hormone Stimulation Test Results Started 2 versus 4 Hours after Trilostane Administration in Dogs with Naturally Occurring Hyperadrenocorticism

Background

Trilostane medical treatment of naturally occurring hyperadrenocorticism (NOH) in dogs is common, as is use of the adrenocorticotropic hormone (ACTH) stimulation test (ACTHst) in monitoring response to treatment. There is uncertainty regarding when the ACTHst should be started relative to time of trilostane administration.

Objective

To compare ACTHst results in dogs being treated for NOH with trilostane when the test is begun 2 versus 4 hours after trilostane administration.

Animals

Twenty‐one privately owned dogs with NOH, each treated with trilostane for at least 30 days.

Methods

Each dog had 2 ACTHst completed, 1 started 2 hours and the other 4 hours after trilostane administration. The second test was started no sooner than 46 hours and no later than 74 hours after the first.

Results

For all 21 dogs, the mean post‐ACTH serum cortisol concentration from tests started 2 hours after trilostane administration (5.4 ± 3.7 μg/dL) was significantly lower (P = .03) as compared with results from the tests started 4 hours after administration (6.5 ± 4.5 μg/dL).

Conclusions

Results of ACTHst started at different times yield significantly different results. Dogs with NOH, treated with trilostane, and monitored with ACTHst results should have all of their subsequent ACTHst tests begun at or about the same time after trilostane administration.     

Dobutamine Stress Echocardiography for Assessment of Systolic Function in Dogs with Experimentally Induced Mitral Regurgitation

Background

Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation (MR).

Hypothesis

We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2‐dimensional speckle‐tracking echocardiography (2D‐STE) could quantitatively evaluate myocardial function.

Animals

Anesthetized dogs with experimentally induced MR.

Methods

Dogs were examined for systolic myocardial deformations using 2D‐STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated.

Results

Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre‐MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre‐MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt (r = 0.644, P < .001; r = 0.696, P < .001).

Conclusions and Clinical Importance

Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR.     

Hypomagnesemia in Brachycephalic Dogs

Background

Brachycephalic dogs are at risk for arterial hypertension and obstructive sleep apnea, which are both associated with chronic magnesium (Mg) depletion.

Hypothesis/Objectives

To compare the period prevalence of hypomagnesemia between Boxers and Bulldogs presented to a referral teaching hospital. To screen a group of Bulldogs for evidence of hypomagnesemia, and to obtain pilot data regarding the utility of parenteral Mg tolerance testing (PMgTT) in the diagnosis of whole‐body Mg deficiency.

Animals

Chemistry laboratory submissions were retrospectively analyzed for serum total Mg (tMg) in Boxers and Bulldogs. Prospectively, 16 healthy client‐owned Bulldogs were enrolled.

Methods

Retrospective case study. tMg concentrations were compared between Boxers and Bulldogs. Dogs with low serum albumin or high serum creatinine concentrations were excluded. Prospectively, ionized Mg (iMg), tMg, and arterial blood pressure were measured and iMg‐to‐tMg ratio (iMg : tMg) was calculated. Parenteral Mg tolerance testing (PMgTT) was performed in 3/16 dogs.

Results

In the retrospective study, period prevalence of hypomagnesemia was 4.7% in Boxers and 15% in Bulldogs (P = .02). The risk ratio for hypomagnesemia in Bulldogs was 1.8 when compared to Boxers (CI: 1.3–2.7). In the prospective study, iMg was [median (interquartile)] 0.43 (0.42–0.46) mmol/L (reference range 0.4–0.52), tMg was 1.9 (1.8–1.9) mg/dL (reference range 1.9–2.5). iMg : tMg was [mean (±SD)] 0.59 ± 0.04. Percentage retention after PMgTT were 55%, 95%, and 67%, respectively.

Conclusions and Clinical Importance

Mg deficiency is common in Bulldogs and could contribute to comorbidities often observed in this breed. iMg : tMg and PMgTT might prove helpful in detecting chronic subclinical Mg deficiency.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.     

The Prognostic Value of Perioperative Profiles of ACTH and Cortisol for Recurrence after Transsphenoidal Hypophysectomy in Dogs with Corticotroph Adenomas

Background

Transsphenoidal hypophysectomy is an effective treatment for dogs with pituitary‐dependent hypercortisolism (PDH). However, long‐term recurrence of hypercortisolism is a well‐recognized problem, indicating the need for reliable prognostic indicators.

Objectives

The aim of this study was to evaluate the prognostic value of perioperative plasma ACTH and cortisol concentrations for identifying recurrence of hypercortisolism after transsphenoidal hypophysectomy.

Animals

A total of 112 dogs with PDH that underwent transsphenoidal hypophysectomy met the inclusion criteria of the study.

Methods

Hormone concentrations were measured preoperatively and 1–5 hours after surgery. Both absolute hormone concentrations and postoperative concentrations normalized to preoperative concentrations were included in analyses. The prognostic value of hormone concentrations was studied with Cox''s proportional hazard analysis.

Results

Median follow‐up and disease‐free period were 1096 days and 896 days, respectively. Twenty‐eight percent of patients had recurrence, with a median disease‐free period of 588 days. Both absolute and normalized postoperative cortisol concentrations were significantly higher in dogs with recurrence than in dogs without recurrence. High ACTH 5 hours after surgery, high cortisol 1 and 4 hours after surgery, high normalized ACTH 3 hours after surgery, high normalized cortisol 4 hours after surgery and the random slope of cortisol were associated with a shorter disease‐free period.

Conclusions and clinical importance

Individual perioperative hormone curves provide valuable information about the risk of recurrence after hypophysectomy. However, because no single cutoff point could be identified, combination with other variables, such as the pituitary height/brain area (P/B) ratio, is still needed to obtain a good estimate of the risk for recurrence of hypercortisolism after hypophysectomy.     

Evaluation of resting cortisol concentration testing in dogs with chronic gastrointestinal signs

BackgroundResting 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/ObjectivesTo assess the cross‐sectional prevalence of hypoadrenocorticism in a group of dogs with chronic gastrointestinal signs presented to a referral internal medicine service.AnimalsTwo‐hundred and eighty‐two client‐owned dogs with chronic gastrointestinal signs and with resting cortisol concentration testing performed.MethodsRetrospective 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.ResultsResting 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 ImportanceAlthough 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.     

The Impact of Demographic,Social, and Environmental Factors on the Development of Steroid‐Responsive Meningitis‐Arteritis (SRMA) in the United Kingdom

Background

Steroid‐responsive meningitis‐arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune‐mediated. The development of other immune‐mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed.

Hypothesis/Objectives

To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed.

Animals

Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom.

Methods

Retrospective case‐control study with unconditional logistic regression analysis.

Results

Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA.

Conclusions and Clinical Importance

Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA.     

Qualitative and Quantitative Contrast‐Enhanced Ultrasonographic Assessment of Cerulein‐Induced Acute Pancreatitis in Dogs

Background

Acute pancreatitis (AP) is the most common disease of the canine exocrine pancreas, and accurate noninvasive diagnosis is challenging.

Hypothesis/Objectives

To determine the feasibility of using quantitative contrast‐enhanced ultrasonography (CEUS) to detect pancreatic perfusional changes in cerulein‐induced AP in dogs.

Animals

Six adult female Beagles.

Methods

Each dog received 2 hours of IV infusion with 7.5 μg/kg/h of cerulein diluted in saline. As control, all dogs received 2 hours of IV infusion of saline 2 weeks before cerulein infusion. CEUS of the pancreas and duodenum were performed before (0 hour), and at 2, 4, 6, and 12 hours after saline and cerulein infusion. Time‐intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusional parameters were measured for statistical analysis: time to initial up‐slope, peak time, time to wash‐out, peak intensity (PI), and area under the curve (AUC).

Results

In cerulein‐induced AP, pancreatic PI increased at 2 and 4 hours when compared to 0 hour, and at 2, 4, and 6 hours when compared to control. AUC increased at 4 hours when compared to 0 hour, and at 2 and 4 hours when compared to control. Time to wash‐out was prolonged at 4 hours when compared to control. For saline control, peak time was faster at 2 hours when compared to 0 hour.

Conclusions and Clinical Importance

CEUS parameters PI and AUC can provide useful information in differentiating acute pancreatitis from normal pancreas. Cerulein‐induced AP was characterized by prolonged hyperechoic enhancement on CEUS.     

Serum Biomarkers of Clinical and Cytologic Response in Dogs with Idiopathic Immune‐Mediated Polyarthropathy

Background

Immune‐mediated polyarthopathy (IMPA) is common in dogs, and is monitored by serial arthrocenteses.

Hypothesis/Objectives

Plasma C‐reactive protein (CRP), interleukin‐6 (IL‐6), and CXCL8 (interleukin‐8) would serve as noninvasive markers of joint inflammation in IMPA.

Animals

Nine client‐owned dogs with idiopathic IMPA; 6 healthy controls.

Methods

Prospective study. Plasma CRP, IL‐6, and CXCL8 were measured by ELISA at baseline, 2, and 4 weeks during treatment with prednisone at 50 mg/m²/day. Arthrocenteses, the canine brief pain inventory (CBPI), and accelerometry collars were used to assess joint inflammation, lameness, and mobility at all 3 time points.

Results

C‐reactive protein concentrations were higher in IMPA dogs (median 91.1 μg/mL, range 76.7–195.0) compared with controls (median <6.3 μg/mL, <6.3–13.7; P = .0035), and were significantly lower at week 2 (10.6 μg/mL, <6.3–48.8) and week 4 (<6.3 μg/mL, <6.3–24.4; P < .001).C‐reactive protein was correlated with median CBPI scores (r = 0.68; P = .0004), joint cellularity (r = 0.49, P = .011), and mobility by accelerometry (r = −0.42, P = .048). Plasma IL‐6 concentrations were also higher in IMPA dogs (median 45.9 pg/mL), compared with controls (median <15.7 pg/mL; P = .0008). IL‐6 was lower in IMPA dogs by week 4 (<15.7 pg/mL; P = .0099), and was modestly correlated with CBPI scores (r = 0.47, P = .023). CXCL8 did not differ significantly between IMPA and healthy dogs.

Conclusions

Plasma CRP and IL‐6 might be useful surrogate markers of synovial inflammation and disease activity in dogs with IMPA.     

Discrepancies in Identification of Left Atrial Enlargement Using Left Atrial Volume versus Left Atrial‐to‐Aortic Root Ratio in Dogs

Background

Left atrial size is prognostically important in dogs with myxomatous mitral valve disease (MMVD).

Hypothesis/Objectives

To compare the level of agreement in identification of left atrial enlargement (LAE) between the left atrial‐to‐aortic root ratio (LA : Ao) and left atrial volume using the biplane area‐length method indexed to body weight (LA Vol/BW).

Animals

Sixty dogs with MMVD and 22 normal dogs were prospectively studied with 2‐dimensional echocardiography.

Methods

The upper limit of normal for LA Vol/BW was defined as 1.1 mL/kg. LA : Ao was deemed normal if ≤1.5. To define overall disease severity, each dog was assigned a mitral regurgitation severity score (MRSS) based on echocardiographic parameters that did not include left atrial size. ACVIM staging also was utilized.

Results

Of 60 affected dogs, 20 were ACVIM Stage B1, 25 were Stage B2, and 15 were Stage C. LA Vol/BW identified LAE in 12 cases in which LA : Ao was normal; 7 of these were Stage B1 and 5 were Stage B2. This diagnostic disagreement was significant (P = .00012). Of the 12 cases in which diagnostic discrepancies were identified, 5/5 of the B2 dogs and 3/7 B1 dogs had a moderate MRSS, whereas 4/7 B1 dogs had a mild MRSS. No diagnostic discrepancies between LA : Ao and LA Vol/BW were apparent in dogs with a severe MRSS.

Conclusions and Clinical Importance

This study shows evidence of diagnostic disagreement between LA : Ao and LA Vol/BW for assessment of LAE. LA Vol/BW may be superior to LA : Ao for identification of mild LAE.     

Hypercoagulability in Dogs with Blastomycosis

Background

Blastomycosis is a potentially fatal fungal disease that most commonly affects humans and dogs. The organism causes systemic inflammation and has a predilection for the lungs. The inflammation might lead to a hypercoagulable state with microemboli in the pulmonary circulation which could contribute to inadequate oxygen exchange in infected dogs.

Hypothesis/Objectives

Dogs with blastomycosis will be hypercoagulable compared with healthy case‐matched controls.

Animals

Client‐owned dogs with a diagnosis of blastomycosis (n = 23) and healthy case‐matched controls (n = 23).

Methods

Prospective case‐controlled study of client‐owned dogs presented to a veterinary teaching hospital with clinical signs compatible with blastomycosis. Complete blood counts, fibrinogen, PT, aPTT, thromboelastometry (TE), thrombin antithrombin complexes (TAT), and thrombin generation were evaluated.

Results

Cases had a leukocytosis compared with controls [mean (SD) 16.6 (7.6) × 10³/μL versus 8.2 (1.8) × 10³/μL, P < .001], hyperfibrinogenemia [median 784 mg/dL, range 329–1,443 versus median 178 mg/dL, range 82–257, P < .001], and increased TAT concentrations [mean (SD) 9.0 (5.7) μg/L versus 2.0 (2.8) μg/L, P < .001]. As compared to controls, cases were also hypercoagulable as evaluated by thromboelastometry and had increased in vitro thrombin generation on calibrated automated thrombography.

Conclusions and Clinical Importance

Hypercoagulability occurs in dogs with systemic blastomycosis. Additional studies are needed to explore a possible contribution of thrombogenicity to the clinical manifestations of systemic blastomycosis.