Hypoadrenocorticism in cats – a 40 year update

Practical relevanceAddison’s disease is a very rare condition in cats with only approximately 40 cases documented since it was initially described in the 40 years between 1983 and 2023. Clinical challenges While canine hypoadrenocorticism is a well-recognised disorder with clear diagnostic and treatment guidelines, feline hypoadrenocorticism remains a challenge, due to 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 ACTH stimulation test (ACTHST); 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 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 licenced in UK and mineralocorticoids (desoxycorticosterone pivalate) of which the only available formulation is licenced for dogs and its safety has not been assessed in cats (Zycortal, Dechra, UK).Global importanceFeline hypoadrenocorticism occurs worldwide. Although no breed, sex or age association has been reported, cats below 6 years of age are overrepresented. Evidence baseThe information in this review is compiled from 47 reported cases of feline hypoadrenocorticism. Two retrospective multiple case series are included in this review and report investigating clinical presentation, clinicopathological findings and observational treatment outcomes (EBM grade III) with the remaining being single case reports (EBM grade IV). No prospective, randomised, placebo-controlled studies have been performed regarding feline hypoadrenocorticism (EBM grade I). <br/

Thank you- 2022 JAVMA Reviewers

We sincerely thank our reviewers who served in 2022 for the Journal of the American Veterinary Medical Association as their contributions have made possible our mission to advance and promote the science and art of veterinary medicine while upholding world-class standards in peer-reviewed veterinary medical scientific publication

Diagnostic yield of percutaneous, ultrasound-guided, fine needle aspirates of the gastrointestinal wall: a retrospective analysis of 152 samples

Objectives: The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success. Secondary aims included comparing the cytological diagnosis with histopathology, evaluating the utility of concurrent locoregional lymph node cytology and assessing the procedure's complication rate. Material and Methods: Gastrointestinal wall cytology from 75 dogs and 70 cats obtained between 2018 and 2023 were reviewed and categorised as successful (resulting in a diagnostic cytology report) and accurate (resulting in the correct diagnosis when compared to histopathology). Unsuccessful fine needle aspirates, not submitted for cytology, were not recorded. Variables recorded included animal signalment, lesion and lymph node's appearance on ultrasound, size, location, number of smears submitted and experience of the ultrasonographer. Results: One hundred and fifty-two reports were analysed. Eighty-eight (58%) were successful: three normal epithelium, 21 inflammatory processes and 64 neoplasms. Variables associated with increased technical success included description of a mass, higher number of slides submitted and thickness of gastrointestinal lesion on ultrasound. Comparison with histopathology, performed for 17 lesions, showed discrepancies in eight, complete agreement in seven and partial in two. Eighty-four loco-regional lymph nodes were sampled, of which, 67 were successful (80%) and 52 brought additional clinical information (supporting GI wall cytology or diagnosing neoplasia not identified on GI wall cytology). No complication strictly attributable to gastrointestinal wall sampling was reported but when possibly related, death of the patient occurred in 2.5% of cases. Clinical Significance: Ultrasound-guided fine needle aspirate of gastrointestinal wall had moderate accuracy and was unsuccessful in 42% of cases, but technical success increased when sampling mass lesions, thicker intestinal layers and submitting more slides.</p

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 (3β hydroxysteroid dehydrogenase; 3βHSD) 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 3βHSD, 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

Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

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)

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:Peer reviewe