Robert Shiel

Simple Summary
After having achieved international consensus over disease, diagnosis, classification, and monitoring concepts in the area of companion animal diabetes mellitus, Cushing’s syndrome, and hypoadrenocorticism, a group of 14 experts and one chair embarked on the third cycle of project “Agreeing Language in Veterinary Endocrinology” (ALIVE), this time focusing on thyroid disease terminology. This cycle’s methods followed, like previous ones, a modified Delphi-approach with small changes to improve efficiency and flexibility, including an off-site chair. For the first time, additionally, feedback on definitions of a previous cycle was incorporated, leading to an update of diabetes mellitus related definitions of ALIVE Cycle 1. This third cycle was completed successfully, accomplishing a majority-based consensus among panellists and international veterinary endocrinology society memberships over 78 thyroid related terminology and five updated diabetes mellitus definitions. As has been the case with the definitions created for other hormonal diseases, it is hoped this work will improve education, research, diagnosis, and treatment in cats and dogs with endocrine disease.

Abstract
Companion animal endocrinology has benefited from international standardisation of disease terminology for diabetes mellitus, Cushing’s syndrome, and hypoadrenocorticism through Project Agreeing Language in Veterinary Endocrinology (ALIVE). A group of 14 experts and one chair convened for the third cycle of Project ALIVE, focusing on thyroid disease terminology. The cycle employed the modified Delphi approach from previous cycles, augmented by procedural refinements—such as inclusion of an off-site chair and stricter adherence to timelines —to improve efficiency and flexibility. Novel in this round was the integration of feedback from a previous cycle, which resulted in updated definitions for diabetes mellitus originally developed in ALIVE Cycle 1. Outcomes: A 100% consensus was achieved among panellists and 91.4–100% among 105 members of international veterinary endocrinology societies (32% of total memberships) over 78 thyroid-related terminology items and five revised definitions pertaining to diabetes mellitus. These standardised definitions are expected to facilitate clearer communication and education, enhance diagnostic consistency, support research comparability, and improve clinical care in feline and canine endocrine diseases.

Naturally occurring hypercortisolism in dogs is commonly investigated in primary care practice. However, there is a poor understanding of the preference and interpretation of diagnostic tests by Australian veterinarians. This study aimed to investigate the diagnostic processes used by Australian primary care veterinarians via an anonymous online survey consisting of multiple-choice and short-answer questions. The survey was completed by 399 respondents. When hypercortisolism was suspected, 392 performed adrenal function testing, while seven used treatment trials. With consistent clinical signs but no clinicopathological abnormalities, 354 performed screening tests, and 312 in dogs with consistent clinicopathological abnormalities but no clinical signs. For veterinarians who performed function testing, 296 used the same screening tests regardless of the magnitude of pre-test suspicion; 266 used either an adrenocorticotropic hormone (ACTH) stimulation test or low-dose dexamethasone suppression test (LDDST) alone. Even in the absence of financial constraints, 158 of 399 respondents almost never attempted differentiation between ACTH-dependent and ACTH-independent disease. For those attempting differentiation, 178 used abdominal ultrasound and 102 used LDDST. Approximately half of all respondents indicated that specialist referral was not offered to any of the preceding 10 cases suspected of hypercortisolism. Hypercortisolism is frequently diagnosed in dogs without consistent clinical signs or without performing routine clinical pathology tests, raising concerns for overdiagnosis. A large proportion of respondents rarely attempted to differentiate between causes of hypercortisolism, possibly affecting long-term management and prognosis. Referral to a specialist is rare, suggesting the condition is predominantly managed in primary care practice.

A 4-year-old, female, neutered Chihuahua cross was presented with a history of chronic apparent vomiting and coughing. Upon further questioning, regurgitation was suspected rather than vomiting. Conscious thoracic radiographs revealed generalised megaoesophagus. The dog was diagnosed with focal myasthenia gravis based on a positive acetylcholine receptor antibody titre 2.33 nmol/L (<0.6 nmol/L). The dog responded to pyridostigmine treatment (0.5 mg/kg every 12 hours, increasing to 1.6 mg/kg every 12 hours) with reduced frequency of regurgitation episodes. In this case, differentiation between vomiting and regurgitation was crucial for appropriate diagnostic testing and treatment. Pyridostigmine is the treatment of choice for both focal and generalised myasthenia gravis. The dose must be titrated to control clinical signs in both forms of the disease.

Background
Feline primary hyperaldosteronism is a relatively rare endocrine disease of geriatric cats. Main clinical features include those derived from hypertension and hypokalaemia. A high index of suspicion of the disease is required since clinical signs and clinicopathological features can be confused with those of chronic kidney disease. The diagnosis involves the routine clinical pathology, diagnostic imaging and assessment of hormone concentrations, and potentially dynamic functional testing. Treatment could be surgical or medical depending on the cause of the disease.

Aim of the article
To review the pathophysiology of primary hyperaldosteronism, summarising the currently available literature about the disease. The article also aims to provide practical suggestions for the diagnostic investigation of cats with suspected primary hyperaldosteronism, and for treatment of the disease.

Sepsis and septic shock are leading causes of morbidity and mortality in both humans and dogs, and early diagnosis is crucial for improving outcomes. This study aimed to evaluate bioactive adrenomedullin (bio-ADM) concentrations in dogs with septic shock (n = 25), dogs with sepsis without evidence of shock (n = 25), and healthy control dogs (n = 25). Plasma bio-ADM concentrations were measured using a human sandwich enzyme-linked immunosorbent assay and reported as median (interquartile range). Plasma bio-ADM concentrations were significantly higher in both septic groups compared to the healthy controls (all <22.4 pg/mL), but not significantly different between the septic shock (75.0 [28.7–115.0] pg/mL) and sepsis (30.7 [22.4–79.7] pg/mL) groups. Dogs with higher illness severity scores had significantly higher bio-ADM concentrations (93.1 [32.2–122.0] pg/mL) than those with lower scores (29.8 [22.4–71.2] pg/mL). However, bio-ADM concentrations did not differ between survivors (33.0 [22.7–76.7] pg/mL) and non-survivors (74.7 [26.1–123.2] pg/mL). Measurement of bio-ADM is a potential marker for canine sepsis, but not for the identification of septic shock, and may provide information on disease severity. Further studies, including those on non-infectious inflammatory conditions, are necessary to better understand the diagnostic utility of bio-ADM measurement and its potential role as a marker of treatment response in dogs with sepsis.

Background
Naturally occurring hypoadrenocorticism is an uncommon endocrine disorder in dogs but has significant morbidity and mortality. Some dogs present with apparent glucocorticoid deficiency alone as evidenced by eunatraemia and eukalaemia. Few studies have compared dogs with hypoadrenocorticism with or without electrolyte disturbances and there are no large case series of affected dogs from Ireland.

Methods
Retrospective observational study.

Results
Ninety-two cases diagnosed with hypoadrenocorticism subdivided into those with supportive electrolyte disturbances (Group 1; n = 72) and those without (Group 2; n = 20). Dogs in Group 1 were significantly (p = 0.001) younger (4.0 (3.0–6.0) years) than dogs in Group 2 (6.0 (4.75–8.25) years). Dogs in Group 1 presented significantly more commonly with vomiting (Group 1: 52/71 (73.2%), Group 2: 6/20 (30.0%); p < 0.001), total hyperproteinaemia (Group 1: 21/71 (29.6%), Group 2: 1/20 (5.0%); p = 0.023), increased urea (Group 1: 52/72 (72.2%), Group 2: 5/20 (25.0%); p < 0.001), increased creatinine (Group 1: 31/72 (43.1%), Group 2: 3/20 (15.0%); p = 0.021) and hyperphosphataemia (Group 1: 40/71 (56.3%), Group 2: 2/20 (10.0%); p < 0.001), and significantly less commonly with reticulocytosis (Group 1: 4/38 (10.5%), Group 2: 5/13 (38.5%), p = 0.023). An undetectable basal aldosterone concentration had a positive predictive value of 94.3% for diagnosing undetectable post-ACTH aldosterone concentration. Of the thirteen dogs in Group 2 that had aldosterone concentrations measured and secondary disease excluded, 7 (53.8%) had or subsequently developed evidence of aldosterone deficiency, although not always with electrolyte abnormalities.

Conclusions
Dogs with hypoadrenocorticism from Ireland are similar to other reported cases. An undetectable basal aldosterone concentration is highly predictive of mineralocorticoid deficiency. Dogs with apparent glucocorticoid deficiency alone can progress to more typical disease and should be monitored appropriately.

Background
Ultrasound-determined gallbladder wall thickness is widely used to aid in the diagnosis of gallbladder disease, but no reference values supported by published measurement data are available in dogs.

Hypothesis/Objective
Establish normal thickness of the gallbladder wall in dogs.

Animals
Fifty-three dogs presented to a referral hospital and required abdominal ultrasound examination for reasons unrelated to primary hepatobiliary disease.

Methods
Cross-sectional observational study recruiting dogs requiring abdominal ultrasound examination. A standard sequence of gallbladder wall images was recorded for later review. Inclusion criteria were normal ultrasonographic hepatobiliary, pancreatic, and small intestinal findings. Exclusion was determined by 2 European College of Veterinary Internal Medicine (ECVIM)-certified veterinary internists blinded to gallbladder wall thickness data. Dogs were excluded if they had inadequate medical records, a previous history of hepatobiliary, gastrointestinal, or pancreatic disease likely to impact the biliary system (eg, chronic vomiting, nausea, jaundice, diarrhea), unexplained increases in liver enzyme activities, hypoalbuminemia, or ascites. Gallbladder wall thickness was determined by 2 European College of Veterinary Diagnostic Imaging (ECVDI)-certified veterinary radiologists working together to generate a consensus for each dog. The final output was the maximum normal wall thickness for this population of dogs.

Results
The upper limit for gallbladder wall thickness in 53 fasted (8 hours) dogs <40 kg was 1.30 mm (90% confidence interval, 1.19-1.41).

Conclusions and Clinical Importance
Normal gallbladder wall thickness in dogs is lower than previously reported. Additional studies are required to determine potential effects of body weight and the optimal cut-off to distinguish between healthy and diseased gallbladders.

Objectives: The primary goals of this retrospective study were to describe a population of dogs with portal hypertension secondary to liver disease, and to assess whether prognosis could be inferred from historical, clinical, and clinicopathological data.

Animals and procedures: Dogs (N = 76) diagnosed with intrahepatic portal hypertension between 2011 and 2020 were included; dogs with known congenital hepatic anomalies were excluded. Effect on survival was assessed using univariable and multivariable Cox proportional hazards models for historical, clinical, and clinicopathological variables.

Results: Dogs survived for a median of 14 d (range: 0 to 2028 d), with 31.6% being euthanized within 2 d of diagnosis and 23.7% surviving longer than 2 mo. Presence of jaundice and duration of clinical signs, expressed in days, were significantly associated with outcome in the univariable analysis (HR = 1.846, 95% CI: 1.094 to 3.117, P = 0.02; HR = 0.995, 95% CI: 0.990 to 1.000, P = 0.033, respectively). However, only presence of jaundice was significantly associated with increased hazard of death in the multivariable analysis.

Conclusion: Results of this study show that portal hypertension is associated with a poor prognosis; however, some dogs can show prolonged survival.

Clinical relevance: Clinical data can guide decision-making for clinicians and owners.

Formalin-Fixed Paraffin Embedded (FFPE) biopsies would provide a critical mass of cases to allow investigation of canine liver disease, however their use is often limited by challenges typically associated with transcriptomic analysis. This study evaluates the capability of NanoString® to measure the expression of a broad panel of genes in FFPE liver samples. RNA was isolated from matched histopathologically normal liver samples using FFPE (n = 6) and snap frozen in liquid nitrogen (n = 6) and measured using a custom NanoString® panel. Out of the 40 targets on the panel, 27 and 23 targets were above threshold for non-diseased snap frozen and FFPE tissue respectively. The binding density and total counts were significantly reduced in the FFPE samples relative to the snap frozen samples (p = 0.005, p = 0.01, respectively), confirming a reduction in sensitivity. The concordance between the snap frozen and FFPE samples was high, with correlations (R) ranging between 0.88 and 0.99 between the paired samples. An additional 14 immune-related targets, undetectable the non-diseased FFPE liver, were above threshold when the technique was applied to a series of diseased samples, further supporting their inclusion on this panel. This use of NanoString® based analysis opens up huge opportunity for retrospective evaluation of gene signatures in larger caseloads through harnessing the capacity of archived FFPE samples This information used alongside clinical and histological data will not only afford a way to explore disease etiopathogenesis, it may also offer insight into sub-types of liver disease in dogs, which cannot be discerned using more traditional diagnostic methods.

Hypoadrenocorticism is characterized by a reduction in mineralocorticoid and/or glucocorticoid production by the adrenal glands. Several subtypes have been described with different clinical and clinicopathological consequences. Most affected dogs have vague and non-specific signs that precede an eventual life-threatening crisis. This review aims to appraise classification, the available data on epidemiology and the clinical and laboratory features of naturally occurring canine hypoadrenocorticism.
Canine hypoadrenocorticism is a relatively uncommon endocrine disease that can present with a wide variety of clinical signs resulting from cortisol or aldosterone deficiency or both. Hypoadrenocorticism should be considered in all dogs with severe illness and typical electrolyte abnormalities but also in those with waxing and waning clinical signs. Multiple clinical and laboratory features are suggestive of the disease and should prompt evaluation of adrenal function. The ACTH stimulation test is the best test for diagnosing hypoadrenocorticism but, in those cases without the typical presentation, evaluation of aldosterone secretory capacity and endogenous ACTH concentrations should be performed to distinguish primary from secondary disease. In this review we discuss the pathophysiology of the disease, the clinical signs and laboratory features that should raise suspicion of hypoadrenocorticism and the performance of the different diagnostic tests.