Expert Veterinary Internal Medicine and Endocrinology Consulting Services
We will be posting commentaries on articles relating to internal medicine and endocrinology that we think are of interest.
Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: A multicenter study
June 24th, 2020
Signs of gastrointestinal disease (SGD) secondary to a lack of glucocorticoids are indistinguishable from clinical signs caused by primary GI disorders. In the absence of electrolyte abnormalities, subtle laboratory abnormalities might lead to a suspicion of HA. These can include the lack of a stress leukogram, relative or absolute lymphocytosis, eosinophilia, prerenal azotemia, hypoalbuminemia, hypoglycemia or hypercalcemia. However, these changes are nonspecific, have a number of possible causes and do not help to discriminate primary GI disease from HA.
Hence, diagnosis of HA, especially GDH, is dependent on adrenal gland function testing, such as ACTH-stimulation test (ACTHST). This multicenter study was conducted in order to evaluate the necessity of performing this relatively expensive and time-consuming test in dogs with chronic SGD. The primary aim was to assess the prevalence of HA in dogs with chronic SGD. The secondary aim was to identify clinical and laboratory variables that might help to identify or exclude HA in this group of dogs before performing ACTHST, especially in comparison to other dogs with chronic SGD that do not have HA.
Background: Dogs with hypoadrenocorticism (HA) frequently show signs of gastrointestinal disease (SGD). The prevalence of dogs presented for chronic SGD with HA is unknown.
Objectives: The aims of this study were to determine the prevalence of HA in dogs with chronic SGD and to identify clinical and laboratory variables for HA in this population.
Animals: One hundred fifty-one dogs with chronic SGD.
Methods: In this multicentered prevalence study a standardized workup was performed in prospectively enrolled dogs with SGD > 3 weeks duration. Basal serum cortisol concentration was measured in every dog with ACTH stimulation test (ACTHST) if basal serum cortisol concentration was <3 μg/dL.
Results: Basal serum cortisol concentration was <3 μg/dL in 80/151 (53%) dogs, <2 μg/dL in 42/151 (28%) dogs, and < 1 μg/dL in 9/151 (6%) dogs. In 6/151 dogs HA was diagnosed based on ACTHST (stimulated serum cortisol concentration < 2 μg/ dL), a prevalence of 4%. There was no difference in history, physical examination, and laboratory variables between dogs with HA and those with other causes of chronic SGD. In 4/6 dogs with HA, there was melena or hematochezia indicating gastrointestinal blood loss. Hyperkalemia, hyponatremia, or both was not observed in any dog.
Conclusion and Clinical Importance: The prevalence of HA among dogs with chronic SGD is higher than in the general population. Based on these results, testing adrenal function should be performed as a standard screening test in dogs with chronic SGD to differentiate between HA and chronic enteropathies.
Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia
June 19th, 2020
Immune-mediated thrombocytopenia (IMT) is a disease in which antibodies bind to platelet surface epitopes and lead to platelet destruction. Resulting thrombocytopenia is severe and risk for spontaneous hemorrhage often develops when platelet counts are <50 000/μL. Immune-mediated hemolytic anemia (IMHA) is diagnosed concurrently in some cases, a condition known as Evan’s syndrome. Treatment for dogs with primary IMT consists of immunosuppression with corticosteroids, alone, or in combination with other immunosuppressive drugs including azathioprine, cyclosporine, and mycophenolate mofetil. Vincristine and human IV immunoglobulin (hIVIG) decrease the time required to restore platelet counts to ≥40 000/μL in affected dogs. Splenectomy also has been used in dogs with refractory IMT.
Therapeutic plasma exchange (TPE) is an extracorporeal treatment in which a patient’s plasma, containing pathogenic substances such as antibodies and antigen-antibody complexes, is removed and exchanged with replacement solutions. In dogs, TPE is emerging as an effective treatment for immune-mediated disorders, including IMHA and myasthenia gravis, but its application in dogs with IMT has not been described previously. With these case reports, we aimed to describe the techniques, complications, and outcomes of TPE in 4 dogs treated for IMT.
Abstract: Therapeutic plasma exchange (TPE) is an emerging treatment for dogs with immune mediated diseases, but reports for treatment of immune-mediated thrombocytopenia (IMT) are lacking. These case reports illustrate the application of centrifugal TPE in 4 dogs with IMT. All dogs presented with severe hemorrhage requiring ≥1 blood transfusions, were unresponsive to conventional treatment or both. Dogs were treated with 3 sequential centrifugal TPE sessions, totaling 4.0 to 4.9 total plasma volumes exchanged per dog. In 3 dogs, TPE was associated with improvement in clinical manifestations of bleeding and platelet count in combination with immunosuppressive drugs. One dog was euthanized after 3 treatments because of persistent severe thrombocytopenia and hemorrhage. Preliminary observations indicate that TPE is safe and may be a useful adjunct in the management of IMT that is severe or refractory to traditional treatment.
Retrospective study of the diagnostic utility of Spec fPL in the assessment of 274 sick cats
May 26th, 2020
Diagnosis of pancreatitis in cats usually involves a combination of clinical suspicion, evaluation of clinical pathology test results, ultrasonographic evidence of pancreatitis, and measurement of serum feline pancreatic lipase immunoreactivity (fPL). Because no gold standard diagnostic test is available, clinicians must assess test results critically in the context of the clinical presentation.
Lipase is secreted by several tissues and hence measuring the total serum activity of this enzyme is of no diagnostic value in the diagnosis of pancreatitis in cats. Pancreatic lipase, however, is exclusively secreted by the pancreas. This was demonstrated in dogs, because dogs with exocrine pancreatic insufficiency had no canine pancreatic lipase immunoreactivity (cPL) in their serum. However, no similar study has been reported in cats. Regardless, the amino acid sequence of feline pancreatic lipase should be different from that of lipase secreted by other tissues, which in turn should generate a specific immunologic response. The IDEXX laboratories developed the Spec fPL, a quantitative ELISA in 2008 for feline PL, as they had for the canine Spec cPL.
Clinical pathology results reported in cats with pancreatitis include hyperbilirubinemia, hypocalcemia, and hypoalbuminemia, but there are conflicting reports on whether or not clinically relevant differences in these variables occur in cats with pancreatitis.
Our aims were to evaluate the diagnostic utility of the Spec fPL test and selected biochemical tests in the diagnosis of pancreatitis in cats presented to a small animal referral teaching hospital in the United Kingdom. Because no gold standard to assess the diagnostic performance of Spec fPL is available, a combination of diagnostic findings (clinical signs and ultrasonography in all cats, histopathology and cytology in some cats) was used to reach a diagnosis of definite, probable, possible, or unlikely pancreatitis.
Background: Serum feline pancreatic lipase immunoreactivity (fPL) commonly is used in the assessment of sick cats suspected to have pancreatitis but its diagnostic utility is debated.
Objectives: To evaluate the diagnostic utility of the Spec fPL test and selected serum biochemistry tests in the diagnosis of pancreatitis in cats.
Animals: Two hundred seventy-four client-owned cats presented to a university teaching hospital in the United Kingdom, from April 2013 to May 2017, in which Spec fPL was measured.
Methods: Cats were classified into 1 of 4 groups based on clinical signs (all cats), ultrasonographic findings (all cats) and histopathological or cytological assessment of the pancreas where available (9 cats) regardless of Spec fPL concentration. The groups were (a) definite pancreatitis (n = 9), (b) probable pancreatitis (n = 49), (c) possible pancreatitis (n = 139), and (d) unlikely pancreatitis (n = 77). Spec fPL and selected serum biochemistry test results were compared among groups.
Results: Serum fPL concentrations >5.3 μg/L were classified as positive and concentrations <3.5 μg/L were classified as negative. There was a significantly (P = .03) lower proportion of false-positive results (cats unlikely to have pancreatitis, n = 77, with a positive fPL, n = 8, 10%) than false-negative results (cats with definite or probable pancreatitis, n = 58, with a negative fPL result, n = 14, 24%). None of the selected biochemical tests were helpful diagnostically.
Conclusion and Clinical Importance: A positive Spec fPL result indicates that pancreatitis is a probable diagnosis, but the test cannot be used to rule the diagnosis out.
In conclusion, our study supported the use of Spec fPL as part of the diagnostic evaluation of cats with suspected pancreatitis. However, our results must be interpreted with caution. A positive result increases the likelihood of the diagnosis, because in our study and others, the false-positive rate appears to be low. It cannot, however, be used to rule out pancreatitis as a diagnosis because the false negative rate is relatively high. Approximately 25% of the cases classified as definite or probable pancreatitis in our study would have been missed if Spec fPL was the only diagnostic test used. Pancreatitis in cats remains a challenge to diagnose, and results from multiple diagnostic modalities should be assessed when making the diagnosis.
ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs
May 21st, 2020
Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of cardiovascular, respiratory, and systemic diseases. The purpose of this consensus statement is to provide a multidisciplinary approach to guidelines for the diagnosis, classification, treatment, and monitoring of PH in dogs. Comprehensive evaluation including consideration of signalment, clinical signs, echocardiographic parameters, and results of other diagnostic tests supports the diagnosis of PH and allows identification of associated underlying conditions. Dogs with PH can be classified into the following 6 groups: group 1, pulmonary arterial hypertension; group 2, left heart disease; group 3, respiratory disease/ hypoxia; group 4, pulmonary emboli/pulmonary thrombi/pulmonary thromboemboli; group 5, parasitic disease (Dirofilaria and Angiostrongylus); and group 6, disorders that are multifactorial or with unclear mechanisms.
The approach to treatment of PH focuses on strategies to decrease the risk of progression, complications, or both, recommendations to target underlying diseases or factors contributing to PH, and PH-specific treatments. Dogs with PH should be monitored for improvement, static condition, or progression, and any identified underlying disorder should be addressed and monitored simultaneously.
This article is the report of the American College of Veterinary Internal Medicine consensus panel on pulmonary hypertension (PH) in dogs. The panel first established a working definition of PH and then proposed a clinically applicable classification scheme for PH in dogs; with this framework as the basis, practical guidelines for diagnostic, treatment, and monitoring recommendations were developed. Pulmonary hypertension is not a single disorder, and a multidisciplinary approach is optimal. Therefore, the consensus panel was comprised of board-certified specialists in the areas of internal medicine, cardiology, emergency and critical care, diagnostic imaging, and anatomic pathology. The panel initially met in person to outline overall objectives and review the Delphi method for consensus building. Review of the human and veterinary medical literature, development of electronic revisions, and conference calls were used to draft the document and, using a modification of the Delphi method, build consensus for recommendations. An advisory panel of 3 additional cardiologists helped develop echocardiographic definitions of PH and guidelines for echocardiographic assessment of PH. After development of a draft of the document, 2 additional advisory panel members were included to provide input and rate each of diagnostic, therapeutic, and monitoring recommendations. The final tally of numbers of panelists (out of 7) and outside experts (out of 5) agreeing with each recommendation was noted, with comments to clarify reasons for any dissent.
Histopathological findings and canine pancreatic lipase immunoreactivity in normal dogs and dogs with inflammatory and neoplastic diseases of the pancreas
May 11th, 2020
If pancreatitis is suspected, a CBC and serum biochemistry profile are recommended to assess the patient, although changes may be nonspecific. An increase in serum lipase activity might indicate pancreatitis, but depending on the lipase substrate used, results also may be increased in patients with hepatic or renal diseases, well as in those with gastritis. Specific tests, such as radioimmunoassays (RIA) or ELISA, are necessary to distinguish pancreatic-specific lipase from lipase of other origin. However, the 1,2-o-dilaurylrac- glycero-3-glutaric acid-(60-methylresorufin) ester (DGGR) assay shows high correlation with a specific ELISA.
Canine pancreatic lipase immunoreactivity (cPLI) is reported to have variable sensitivity, ranging from 21 to 90.9%, whereas specificity ranges from 74.1 to 100%. Histopathology is widely accepted as the gold standard for the diagnosis of pancreatitis because it is the only method to identify its extent, character and chronicity as well as to distinguish it from neoplastic processes, because of nonspecific gross findings. Cytology also may be useful in the diagnosis of pancreatic carcinoma. Pancreatic biopsy can be performed during abdominal laparotomy. However, both cytology and histopathology are performed infrequently. Ultrasonography is a noninvasive diagnostic tool that avoids tissue damage caused by biopsy sampling. Furthermore, ultrasonography may be useful to differentiate endocrine from exocrine pancreatic tumors, but final diagnosis still requires histopathology.
Our aim was to perform a detailed histopathological characterization of inflammatory and neoplastic pancreatic diseases in dogs and correlate these findings to clinical findings and results of an in-house cPLI assay.
Background: Diagnosis of pancreatic diseases in dogs is still challenging because of variable clinical signs, which do not always correspond with clinical pathology and histopathological findings.
Objectives: To characterize inflammatory and neoplastic pancreatic diseases of dogs and to correlate these findings with clinical findings and canine pancreatic lipase immunoreactivity (cPLI) results.
Animals: Tissue specimens and corresponding blood samples from 72 dogs submitted for routine diagnostic testing.
Methods: Four groups were defined histologically: (1) normal pancreas (n = 40), (2) mild pancreatitis (n = 8), (3) moderate or severe pancreatitis (acute, n = 11; chronic, n = 1), and (4) pancreatic neoplasms (n = 12). An in-house cPLI ELISA (<180 μg/L, normal; >310 μg/L, pancreatitis) was performed.
Results: In dogs with normal pancreas, 92.5% of serum cPLI results were within the reference range and significantly lower than in dogs with mild acute pancreatitis, moderate or severe acute pancreatitis and pancreatic tumors. In dogs with moderate or severe acute pancreatitis, cPLI sensitivity was 90.9% (95% confidence interval [CI], 58.7%-99.8%). Most dogs (9/12) with pancreatic tumors (group 4) had additional pancreatic inflammation and cPLI results were increased in 10 dogs.
Conclusions and Clinical Importance: High cPLI indicates serious acute pancreatitis but underlying pancreatic neoplasms should also be taken into consideration. This study confirms the relevance of histopathology in the diagnostic evaluation of pancreatic diseases
Eating epilepsy is characterized by seizures closely related to eating behavior, which occur in patients with or without spontaneous recurrent seizures (SRS). Seizures triggered by eating (STE) are very rare, and reports in affected humans are sparse. The estimated prevalence is only 1 per 1000 to 2000 of all human patients with epilepsy and 7 per 1000 patients with epilepsy refractory to medical management. It is a unique form of epilepsy frequently classified as reflex with discrete electroencephalographic and clinical signs, and pathophysiological mechanisms that has not been reported previously in dogs.
The purpose of our study was to document the occurrence of STE in dogs, describe their clinical features and their response to treatment. Our hypothesis was that, although rare, STE do occur in dogs and can have variable semiology and pathophysiology.
Background: Seizures triggered by eating (STE) behavior are very rare in humans and
have not been documented previously in dogs.
Objectives: To document the occurrence of STE in dogs and describe their clinical
Animals: Ten client-owned dogs with STE diagnosed at 5 European referral centers.
Methods: A call for suspected cases of STE was made online. This call was followed by a retrospective review of medical records, combined with a questionnaire to be completed by both the owner and the board-certified neurologist who made the diagnosis. Cases were included if >50% of the seizures that occurred were related to eating and if a minimum diagnostic evaluation for seizures had been performed.
Results: Four cases only had STE and 6 cases had both STE and spontaneous seizures. Four of the dogs were retrievers. The most common seizure type was focal epileptic seizures evolving to become generalized. Nine dogs were diagnosed with idiopathic epilepsy. One dog had a presumptive diagnosis of glioma involving the margins of the parietal, temporal, and frontal cortex (the perisylvian region), an area known to have a key role in eating-associated epilepsy in people. Treatment strategies included a combination of pharmacological management and eating habit changes.
Conclusions and Clinical Importance: We have identified a form of reflex epilepsy in dogs, with STE behavior. Further studies are warranted to improve the characterization and management of STE.
Heart murmurs in apparently healthy cats caused by iatrogenic dynamic right ventricular outflow tract obstruction
May 1st, 2020
Pathological and non-pathological causes of heart murmurs however can coexist in apparently healthy cats, and these murmurs cannot be accurately assessed by auscultation alone. Therefore, Doppler echocardiographic evaluation ultimately is required to identify the cause of blood flow turbulence responsible for this clinical finding.
Nevertheless, even Doppler echocardiography performed by experienced clinicians occasionally can fail to identify the origin of murmurs in cats, and failure to identify the cause of a murmur and classify it as either pathological or benign can lead to uncertain prognosis and unnecessary owner anxiety.
Over the last decade, we have incidentally observed that applying gentle pressure with the ultrasound transducer to the right side of the chest wall of a cat can induce temporary narrowing of the mid-RV lumen, iatrogenically inducing DRVOTO and subsequently evoking blood flow turbulence. We also have observed that a similar phenomenon can be reproduced by gently pressing the stethoscope head against the right chest wall of the cat, inducing an audible murmur during auscultation. Therefore, our main objective was to evaluate the effect of increased pressure of the ultrasound transducer against the chest wall of apparently healthy cats during echocardiographic examination on RV outflow velocity. We hypothesized that such a maneuver would increase RV outflow velocity, ultimately resulting in blood flow turbulence in this anatomical area. We also hypothesized that this effect is independent of changes in heart rate during this test.
Background: Heart murmurs are detected commonly in apparently healthy cats during routine physical examination, and Doppler echocardiography ultimately is required to identify the source of flow turbulence causing the murmur. However, in some cases, the origin of the murmur cannot be identified on echocardiographic examination, even by experienced clinicians. The application of gentle pressure with the ultrasound transducer against the chest wall of a cat can induce temporary narrowing of the mid-right ventricular (RV) lumen, causing blood flow turbulence even in the absence of cardiac abnormalities.
Objectives/Hypotheses: To evaluate the effect of pressure of the ultrasound transducer against the chest wall of cats during echocardiography (provocative testing) on RV blood flow. The main hypothesis is that provocative testing can increase RV outflow velocity and cause flow turbulence. The second hypothesis is that the effect of this maneuver is independent of changes in heart rate during testing.
Animals: Sixty-one client-owned, apparently healthy cats with heart murmurs on physical examination.
Methods: Retrospective review of echocardiographic examinations of 723 cats presented for investigation of a heart murmur.
Results: Outflow systolic velocity increased from 1.05 ± 0.26 to 1.94 ± 0.51 m/s during provocative testing (P < .0001); no correlation was found between RV outflow peak velocity and heart rate during provocative testing (P = .34; r = 0.1237).
Conclusions and Clinical Relevance: Right ventricular outflow tract obstruction and associated heart murmur can be iatrogenically induced in apparently healthy cats by increasing pressure on the right chest wall with an ultrasound probe.
Clinical features and radiographic findings in cats with eosinophilic, neutrophilic, and mixed airway inflammation (2011-2018)
April 27th, 2020
Inflammatory airway disease (IAD) is common in cats and is an important differential diagnosis for cats presenting with a history of cough, wheezing, or increased expiratory effort. Inflammatory airway disease has been proposed to encompass 2 distinct syndromes: asthma and chronic bronchitis. Asthma in cats is considered to be similar to asthma in humans and is characterized by increased airway responsiveness and bronchoconstriction, manifested by acute wheezing or respiratory difficulty, which can be reversed by treatment with a bronchodilator. Similar to some forms of the syndrome in humans, asthma in cats has been suggested to result from exposure to allergens, and a disease syndrome typified by eosinophilic airway inflammation can be created experimentally by allergen or antigen challenge. In contrast, chronic bronchitis in cats is defined by the presence of cough, and bronchoconstriction is not part of the clinical picture. Chronic bronchitis in cats has been defined similarly to the disease in dogs with development of nonseptic suppurative airway inflammation in response to an unknown insult. Currently, the etiopathogenesis of the naturally occurring diseases remains poorly understood, and it is unclear whether asthma and chronic bronchitis in cats are separate diseases or part of a spectrum of diseases resulting from inflammation.
In people, differentiation of asthma from bronchitis relies on pulmonary function testing,10 which is not readily applicable to cats. Diagnosis of IAD is based on exclusion of other etiologies such as parasitic, infectious, or neoplastic disease in conjunction with a nonseptic inflammatory infiltrate on airway lavage sampling. Asthma in cats is considered to result in predominantly eosinophilic inflammation and chronic bronchitis in predominantly nonseptic neutrophilic inflammation. However, marked airway eosinophilia has been reported in clinically normal cats and techniques used to collect and evaluate airway samples have been inconsistent across studies. Previous studies evaluating clinical findings in cats with naturally occurring disease have failed to identify clinically relevant differences between cats with asthma and those with chronic bronchitis, with the exception of some investigators noting younger age in cats with airway eosinophilia. The purpose of our retrospective study was to investigate clinical variables that could aid in differentiation between inflammatory airway syndromes in a large group of cats with naturally occurring disease in which standardized diagnostic testing, including bronchoscopic bronchoalveolar lavage (BAL), had been performed.
We hypothesized that cats with eosinophilic inflammation would be younger, have a shorter duration of clinical signs, display less severe radiographic changes, and have higher circulating eosinophil counts compared to those with neutrophilic or mixed airway inflammation.
Background: Idiopathic inflammatory airway disease (IAD) in cats often is described as asthmatic (eosinophilic) or bronchitic (neutrophilic), but this designation requires collection of airway fluid and it fails to consider cats with mixed airway inflammation.
Objective: To identify clinical features that would differentiate inflammatory disease
Animals: Forty-nine cats with nonspecific airway inflammation identified by bronchoscopic
bronchoalveolar lavage (BAL) between 2011 and 2018 were evaluated.
Methods: This is a retrospective study. Cats were categorized by BAL differential cytology as having eosinophilic (eosinophils >20% with neutrophils <14%, or eosinophils >50%), mixed (eosinophils 20%-50% and neutrophils >14% or discordant inflammation from 2 BAL sites), or neutrophilic (neutrophils >14% and eosinophils <20%) inflammation. Type and duration of presenting complaints, signalment, body condition score, respiratory rate, CBC results, bronchoscopy, BAL results (% recovery, total nucleated cell count, differential cell count), and radiographic findings were compared among groups.
Results: Idiopathic IAD was diagnosed in 49 cats, with BAL eosinophilic inflammation in 23, mixed inflammation in 14, and neutrophilic inflammation in 12. Cough was the predominant presenting complaint with no difference in duration of signs among groups (median, 5.5 months). Respiratory rate and effort also did not differ. Cats with eosinophilic inflammation were significantly younger (4.4 ± 3.3 years) than those with neutrophilic (8.0 ±5.6 years) or mixed inflammation (7.5 ± 4.0 years; P = .03). Results of CBC and interpretation of radiographic findings did not differ among groups.
Conclusions and Clinical Importance: Substantial overlap exists in clinical and radiographic findings in cats with various forms of idiopathic airway inflammation.