Hypoadrenocorticism in cats: a 40-year update.

PRACTICAL RELEVANCE: Addison's disease is a very rare condition in cats, with only approximately 40 cases documented in the past 40 years since it was first described in 1983. CLINICAL CHALLENGES: While canine hypoadrenocorticism is a well-recognised disorder with clear diagnostic and treatment guidelines, feline hypoadrenocorticism remains a challenge because of its rarity and waxing and waning clinical signs. Furthermore, empirical treatment with corticosteroids, resulting in clinical improvement, contributes to delays in achieving the diagnosis and initiating treatment. Feline hypoadrenocorticism is diagnosed with an adrenocorticotropic hormone (ACTH) stimulation test; a low resting cortisol concentration with an inadequate or absent response to synthetic ACTH is diagnostic. Various ACTH stimulation-testing protocols are reported in published cases, with the majority using three time-limited blood samples. This can be limiting clinically, depending on cats' clinical presentation and behaviour at the veterinary practice and tolerance for procedures. Long-term treatment, similar to canine hypoadrenocorticism, consists of oral corticosteroids, with several formulations licensed in the UK, and mineralocorticoids (desoxycorticosterone pivalate), of which the only available formulation (Zycortal; Dechra) is licensed for dogs and its safety has not been assessed in cats. GLOBAL IMPORTANCE: Feline hypoadrenocorticism occurs worldwide. Although no breed, sex or age association has been reported, cats aged <6 years are overrepresented.

A retrospective study of hydrocortisone continuous rate infusion compared with administration of dexamethasone boluses in dogs with adrenal crisis.

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.

Evaluation of the utility and accuracy of body fluids containing red blood cells to determine canine and feline blood types.

OBJECTIVE: To examine the accuracy of using body fluids macroscopically suspected to contain erythrocytes to determine the blood type in dogs and cats by use of an immunochromatographic cartridge (ICC), compared to systemic blood as the reference standard. DESIGN: Prospective study. SETTING: University teaching hospital. ANIMALS: Thirty client-owned dogs and 8 cats. INTERVENTIONS: Dogs and cats with a sanguineous or serosanguineous body fluid (SBF) that also required a blood sample were eligible for inclusion. PCV and blood type were determined in all blood and fluid samples. For body fluids with a low PCV and discordant blood type results compared to systemic blood, sample concentration and repeat blood typing from the fluid was performed when enough sample was available. MEASUREMENT AND MAIN RESULTS: Body fluid samples consisted of 16 pleural (11 dogs; 5 cats), 12 peritoneal (10 dogs; 2 cats), and 4 canine pericardial effusions, 3 urine samples, and 1 each of feces and epistaxis from dogs and a seroma sample from a cat. Median (range) manual PCV of blood and fluid samples was 34% (14%-66%) and 6% (0.5%-70%) for dogs and 28% (14%-48%) and 14% (0.5%-19%) for cats, respectively. Dogs were correctly classified as being DEA 1 negative, DEA 1 positive, and DEA 1 weak positive when using body fluid for blood typing 13 of 14, 4 of 9, and 5 of 7, respectively. All reference blood type to fluid blood type (FBT) discordant results had a body fluid PCV equal to or below 2%. Subsequently concentrated body fluid samples had a PCV above 8% and repeat FBT matched reference blood type (RBT). All cats were classified as type A by all RBTs and FBTs. CONCLUSIONS: Body fluids containing erythrocytes may be utilized to blood type dogs if sufficiently concentrated and type A cats.

Serum metabolomic profiles in dogs with chronic enteropathy.

BACKGROUND: Metabolic profiles differ between healthy humans and those with inflammatory bowel disease. Few studies have examined metabolic profiles in dogs with chronic enteropathy (CE). HYPOTHESIS: Serum metabolic profiles of dogs with CE are significantly different from those of healthy dogs. ANIMALS: Fifty-five dogs with CE and 204 healthy controls. METHODS: A cross-sectional study. The serum concentrations of 99 metabolites measured using a canine-specific proton nuclear magnetic resonance spectroscopy platform were studied. A 2-sample unpaired t-test was used to compare the 2 study samples. The threshold for significance was set at P < .05 with a Bonferroni correction for each metabolite group. RESULTS: Nineteen metabolites and 18 indices of lipoprotein composition were significantly different between the CE and healthy dogs. Four metabolites were significantly higher in dogs with CE, including phenylalanine (mean and SD) (healthy: 0.0417 mmol/L; [SD] 0.0100; CE: 0.0480 mmol/L; SD: 0.0125; P value: <.001) and lactate (healthy: 1.8751 mmol/L; SD: 0.7808; CE: 2.4827 mmol/L; SD CE: 1.4166; P value: .003). Fifteen metabolites were significantly lower in dogs with CE, including total fatty acids, and glycine (healthy: 0.2273 mmol/L; SD: 0.0794; CE: 0.1828 mmol/L; SD CE: 0.0517; P value: <.001). CONCLUSIONS AND CLINICAL IMPORTANCE: The metabolic profile of dogs with CE is significantly different from that of healthy dogs, this opens novel research avenues to develop better diagnostic and prognostic approaches as well as therapeutic trials.

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

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.

Xanthogranulomatous Pituitary Adenoma in a Dog with Typical Hyperadrenocorticism.

Xanthogranuloma of the sellar region has been reported in both humans and animals. The lesion is rare, and its aetiology and pathogenesis are not fully understood. The association of sellar xanthogranuloma with an adenoma, known as xanthogranulomatous pituitary adenoma (XPA), is an extremely rare condition in humans and is usually associated with anterior pituitary insufficiencies, headache, vomiting and visual deficits. We present the first report of XPA in an animal. A 7-year-old male neutered Labrador Retriever was presented for investigation of progressive lethargy, vomiting and hyporexia, having been previously diagnosed with chronic kidney disease, pituitary-dependent hyperadrenocorticism and hypoparathyroidism. The dog was euthanized due to lack of response to medical treatment and post-mortem examination revealed XPA. Although rare, xanthogranulomatous lesions should be considered in patients with pituitary disease.

Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism.

BACKGROUND: Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison's disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT). RESULTS: Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites. CONCLUSIONS: This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.

Evaluation of the effect of urine dip vs urine drip on multi-test strip results.

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in-clinic laboratory tests. No independent, evidence-based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe.

Esophageal feeding tube placement and the associated complications in 248 cats.

BACKGROUND: Esophageal feeding tubes are commonly used to provide enteral nutrition to cats, but their use is associated with adverse effects. OBJECTIVES: To evaluate the complications associated with e-tube placement in cats and to identify factors predisposing to these complications. ANIMALS: Cats that had an esophageal feeding tube placed (n = 248). METHODS: This was a retrospective case review in which clinical records were interrogated across 2 referral centers to identify records of cats that had esophageal tubes placed. Clinical data were collected for signalment, clinical indication, method of placement, time of removal, and any complications. Logistic regression was then employed to assess the odds of an increase in complications, including infection and death. RESULTS: For those cats that survived to discharge, tubes were in place for a median of 11 days, ranging from 1 to 93 days. Complications occurred in 35.8% of the cats, with the most common being tube dislodgement (14.5%), followed by stoma site infections (12.1%). Cats receiving glucocorticoids or oncolytic agents (OR = 3.91; 95% CI, 1.14-13.44) and with discharge at the stoma site (OR = 159.8; CI, 18.9-1351) were at an increased odds of developing a stoma site infection, whereas those with a lower weight (OR = 1.33; 95% CI, 1.02-1.75) or (pancreatic [OR = 4.33; 95% CI, 1.02-18.47], neoplastic [OR = 15.44; 95% CI, 3.67-65.07], respiratory [OR = 19.66; 95% CI, 2.81-137.48], urogenital [OR = 5.78; 95% CI, 1.15-28.99], and infectious diseases [OR = 11.57; 95% CI, 2.27-58.94]) had an increased odds of death. The duration of time in place and the cat being discharged with the tube in place were not associated with an increased risk of infection or death. CONCLUSIONS AND CLINICAL IMPORTANCE: Owners should be made aware of the potential risks involved and their predisposing factors.

A longitudinal study of autoantibodies against cytochrome P450 side-chain cleavage enzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism (Addison's disease).

Autoantibodies directed against the P450 side chain cleavage enzyme (P450scc) have been recently described in dogs affected with hypoadrenocorticism, consistent with an immune-mediated pathogenesis of this endocrinopathy. In human autoimmune Addison's disease, autoantibodies may have a predictive value, being detectable before clinical signs developing, and have been shown to persist for a period of time after diagnosis. Furthermore, an autoantibody positive status post-diagnosis has been associated with successful remission of Addison's disease following B-cell depletion, suggesting active immunopathology in these cases. The current study was designed to investigate changes in serum P450scc autoantibody status over time in dogs diagnosed with spontaneous hypoadrenocorticism. P450scc autoantibodies were measured using a species-specific radioimmunoprecipitation assay in an initial cohort of 213 dogs, indicating a prevalence of 24%. Thirty two of these dogs had repeat samples (n = 80 in total) available for analysis. Five dogs were consistently P450scc autoantibody positive in all samples, for up to 425 days following first sampling. Three dogs were initially autoantibody positive, then became seronegative at later time points. One dog, a 1 year old female entire standard poodle, was initially negative for P450scc autoantibodies, but seroconverted 18 months after diagnosis. The remaining 23 dogs with multiple samples available were consistently P450scc autoantibody negative. Persistence was not associated with sex (p = .673). This study demonstrates persistence of P450scc autoantibodies in a subset of dogs affected with hypoadrenocorticism and seroconversion over one year post-diagnosis. P450scc autoantibody reactivity in human autoimmune Addison's disease has been associated with sex, with females having a higher prevalence, possibly due to P450scc expression in the ovary acting as an additional source of antigenic stimulation. However, there was no sex difference in autoantibody persistence in the dogs affected with hypoadrenocorticism. Autontibody persistence in dogs with hypoadrenocorticism might represent persistent pathology, due to residual antigenic stimulation and autoimmune inflammation in the adrenal gland.

Single nucleotide polymorphisms in major histocompatibility class II haplotypes are associated with potential resistance to inflammatory bowel disease in German shepherd dogs.

German shepherd dogs (GSD) in the UK are at increased risk of developing the Inflammatory Bowel Disaese (IBD). IBD is believed to be a multifactorial immune mediated disease affecting genetically predisposed dogs. The aim of the current study was to investigate whether susceptibility to IBD in GSD is associated with the major histocompatibility complex (MHC) class II locus (Dog Leukocyte Antigen, DLA). Sequence-based genotyping of the three polymorphic DLA genes DLA-DRB1, -DQA1 and -DQB1 was performed in 56 GSDs affected by IBD and in 50 breed-matched controls without any history of gastrointestinal signs. The haplotype DLA-DRB1*015:02-DQA1*006:01-DQB1*023:01 was found to be present only in the control population and was associated with a reduced risk of IBD (P<0.001). In contrast, the haplotype DLA-DRB1*015:01-DQA1*006:01-DQB1*003:01 was associated with IBD (Odds ratio [OR]=1.93, confidence interval [CI]=1.02-3.67, P=0.05). This study has identified an association between DLA-type and canine IBD, supporting the immunogenetic aetiology and immunopathogenesis of this disease.

Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).

Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3ß hydroxysteroid dehydrogenase; 3ßHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3ßHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.

Analysis of DLA-DQB1 and polymorphisms in CTLA4 in Cocker spaniels affected with immune-mediated haemolytic anaemia.

BACKGROUND: Cocker spaniels are predisposed to immune-mediated haemolytic anaemia (IMHA), suggesting that genetic factors influence disease susceptibility. Dog leukocyte antigen (DLA) class II genes encode major histocompatibility complex (MHC) molecules that are involved in antigen presentation to CD4(+) T cells. Several DLA haplotypes have been associated with autoimmune disease, including IMHA, in dogs, and breed specific differences have been identified. Cytotoxic T lymphocyte antigen 4 (CTLA4) is a critical molecule involved in the regulation of T-cell responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 promoter have been shown to be associated with several autoimmune diseases in humans and more recently with diabetes mellitus and hypoadrenocorticism in dogs. The aim of the present study was to investigate whether DLA-DQB1 alleles or CTLA4 promoter variability are associated with risk of IMHA in Cocker spaniels. RESULTS: There were a restricted number of DLA-DQB1 alleles identified, with a high prevalence of DLA-DQB1*007:01 in both groups. A high prevalence of DLA-DQB1 homozygosity was identified, although there was no significant difference between IMHA cases and controls. CTLA4 promoter haplotype diversity was limited in Cocker spaniels, with all dogs expressing at least one copy of haplotype 8. There was no significant difference comparing haplotypes in the IMHA affected group versus control group (p = 0.23). Homozygosity for haplotype 8 was common in Cocker spaniels with IMHA (27/29; 93 %) and in controls (52/63; 83 %), with no statistically significant difference in prevalence between the two groups (p = 0.22). CONCLUSIONS: DLA-DQB1 allele and CTLA4 promoter haplotype were not found to be significantly associated with IMHA in Cocker spaniels. Homozygosity for DLA-DQB1*007:01 and the presence of CTLA4 haplotype 8 in Cocker spaniels might increase overall susceptibility to IMHA in this breed, with other genetic and environmental factors involved in disease expression and progression.

Vitamin D status predicts 30 day mortality in hospitalised cats.

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats.

A review of the genetics of hypoadrenocorticism.

Hypoadrenocorticism is an uncommon disease in dogs and rare in humans, where it is known as Addison disease (ADD). The disease is characterized by a deficiency in corticosteroid production from the adrenal cortex, requiring lifelong hormone replacement therapy. When compared with humans, the pathogenesis of hypoadrenocorticism in dogs is not well established, although the evidence supports a similar autoimmune etiology of adrenocortical pathology. Several immune response genes have been implicated in determining susceptibility to Addison disease in humans, some of which are shared with other autoimmune syndromes. Indeed, other types of autoimmune disease are common (approximately 50%) in patients affected with ADD. Several lines of evidence suggest a genetic component to the etiology of canine hypoadrenocorticism. Certain dog breeds are overrepresented in epidemiologic studies, reflecting a likely genetic influence, supported by data from pedigree analysis. Molecular genetic studies have identified similar genes and signaling pathways, involved in ADD in humans, to be also associated with susceptibility to canine hypoadrenocorticism. Immune response genes such as the dog leukocyte antigen (DLA) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) genes seem to be particularly important. It is clear that there are genetic factors involved in determining susceptibility to canine hypoadrenocorticism, although similar to the situation in humans, this is likely to represent a complex genetic disorder.

A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds.

Canine hypoadrenocorticism is believed to be an immune-related condition. It is rare in the overall dog population but shows a breed-related predisposition with Standard poodles and Portuguese water dogs having a greater prevalence of the condition. It shares many similarities with human primary adrenal insufficiency and is believed to be a naturally occurring, spontaneous model for the human condition. Short haplotype blocks and low levels of linkage disequilibrium in the human genome mean that the identification of genetic contributors to the condition requires large sample numbers. Pedigree dogs have high linkage disequilibrium and long haplotypes within a breed, increasing the potential of identifying novel genes that contribute to canine genetic disease. We investigated 222 SNPs from 42 genes that have been associated or may be implicated in human Addison's disease. We conducted case-control analyses in 3 pedigree dog breeds (Labrador retriever: affected n = 30, unaffected = 76; Cocker Spaniel: affected n = 19, unaffected = 53; Springer spaniel: affected n = 26, unaffected = 46) and identified 8 associated alleles in genes COL4A4, OSBPL9, CTLA4, PTPN22, and STXBP5 in 3 pedigree breeds. Association with immune response genes PTPN22 and CTLA4 in certain breeds suggests an underlying immunopathogenesis of the disease. These results suggest that canine hypoadrenocorticism could be a useful model for studying comparative genetics relevant to human Addison's disease.

MHC class II association study in eight breeds of dog with hypoadrenocorticism.

Canine hypoadrenocorticism is an endocrine disorder characterised by inadequate secretion of steroid hormones from the adrenal glands. Pathology results from immune-mediated destruction of the adrenal cortex, which is similar to that seen in the human Addison's disease. Both the canine and human diseases have similar clinical presentation, with the diagnosis based on performing a dynamic adrenocorticotropic hormone stimulation test. MHC class II has previously been associated with the human and canine diseases. In the current study, we conducted an MHC class II association study in eight breeds of dog with diagnoses of hypoadrenocorticism. We demonstrated significant differences in dog leukocyte antigen (DLA) haplotype frequencies in six of these breeds: Cocker spaniel, Springer spaniel, Labrador, West Highland white terrier (WHWT), Bearded collie, and Standard poodle. In the Springer spaniel, the DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01 haplotype was significantly associated with disease risk (p = 0.014, odds ratio (OR) = 5.14) and showed a similar trend in the Cocker spaniel. This haplotype is related to one associated with hypoadrenocorticism in the Nova Scotia duck tolling retriever. Similar haplotypes shared between breeds were demonstrated, with DLA-DRB1*001:01--DQA1*001:01--DQB1*002:01 more prevalent in both affected Labrador (p = 0.0002, OR = 3.06) and WHWT (p = 0.01, OR = 2.11). Other haplotypes that have not previously been associated with the disease were identified. The inter-breed differences in DLA haplotypes associated with susceptibility to canine hypoadrenocorticism could represent divergent aetiologies. This could have implications for clinical diagnosis and future comparative studies. Alternatively, it may suggest that the gene of interest is closely linked to the MHC.

Assessment of the diagnostic accuracy of circulating natriuretic peptide concentrations to distinguish between cats with cardiac and non-cardiac causes of respiratory distress.

OBJECTIVES: To determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats. ANIMALS: Seventy-four cats from 1 university hospital were used. METHODS: Serum NP concentrations were measured in 41 cats with non-cardiac respiratory distress (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD+CHF) using sandwich enzyme immunoassays (ELISA). RESULTS: RD-NC cats had lower (P=0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL, respectively) than RD+CHF cats (1690 and 523 fmol/mL, respectively). The area under the curve was 0.88 and 0.96 for the receiver operating curve analysis of the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate RD+CHF from RD-NC cats (P=0.036). An optimum cut-off concentration of 986 fmol/mL for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from RC+CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and 87.8%, respectively. CONCLUSIONS: Serum NP concentrations were different in RD+CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations may be helpful in the initial approach to cats presenting with respiratory distress, particularly if advances in ELISA technology result in a rapid cage-side test.