Daniel K. Langlois

Hypercalcemia associated with granulomatous disease in dogs can present a diagnostic challenge. Excessive endogenous, extrarenal calcitriol production is a potential mechanism of ionized hypercalcemia in dogs with granulomatous skin conditions. Hypercalcemic client-owned dogs (n = 7) with chronic skin disease seen in general and specialty practices with calcium profiles submitted to a university veterinary diagnostic laboratory by the attending clinician. Descriptive case series reporting clinical presentation, laboratory findings, treatment, and outcome of 7 hypercalcemic dogs with dermatopathies of varying etiology. Panniculitis was confirmed histologically in 5 dogs (idiopathic, n = 4; presumed bacterial, n = 1). The other 2 dogs had severe generalized demodicosis (n = 1) and demodectic/sarcoptic mange with superficial and deep pyoderma (n = 1). Initial testing showed clinically relevant parathyroid-independent ionized hypercalcemia, undetectable parathyroid hormone-related protein concentration, and 25-hydroxyvitamin D concentration close to or below the lower reference limit in all dogs. Calcitriol concentration was above reference interval in 6 dogs at initial testing, and near the upper reference limit in 1 dog 29 days after presentation. In all cases, normalization of calcium and vitamin D homeostasis paralleled clinical improvement with appropriate therapy for the underlying skin condition. Ionized hypercalcemia apparently mediated by excessive extrarenal calcitriol production can be seen in dogs with granulomatous skin disease. Calcitriol measurement should be included with other calcium-related testing in the workup of unexplained hypercalcemia with concurrent chronic skin disease.

Background: Desoxycorticosterone pivalate (DOCP) is commonly used to treat mineralocorticoid deficiency in dogs with hypoadrenocorticism (HA). Hypothesis/Objective: To determine the pharmacokinetics and pharmacodynamics of DOCP. Animals: Twenty-one dogs with newly diagnosed HA. Methods: Prospective clinical trial. Dogs were randomly assigned to treatment with an SC injection of either 1.1 mg/kg (low-dose) or 2.2 mg/kg (label-dose) DOCP. Blood samples were collected at set time points for measurement of serum drug concentrations, serum electrolyte concentrations, and plasma renin activities (PRAs). A one-compartment model was used to determine pharmacokinetics variables. Pharmacodynamics variables including duration of DOCP action and duration of overtreatment were estimated from serum electrolyte concentrations and PRA. Pharmacokinetics and pharmacodynamics variables were compared between low-dose and label-dose groups. Results: Maximum drug concentrations and overall drug exposures were higher in label-dose dogs (1.22 ± 0.46 ng/mL and 32.1 ± 12.3 day × ng/mL) than in low-dose dogs (0.69 ± 0.32 ng/mL and 19.6 ± 5.3 day × ng/mL; P = .008 for both comparisons). However, duration of DOCP action as determined by PRA in label-dose (55 ± 16 days) and low-dose (45 ± 12 days) dogs was not different (P = .2). Serum electrolyte concentrations overestimated the duration of action in the combined group by a mean of 10 days when compared with PRA (P < .001). Conclusions and clinical importance: Pharmacokinetics and pharmacodynamics data suggest that low-dose DOCP administered every 5-7 weeks is a reasonable treatment strategy for most dogs with HA. Prolonging dosing intervals > 7-8 weeks based solely on electrolyte concentrations should be avoided.

Objective: To investigate changes in gastrointestinal biomarkers over time in dogs undergoing elective orthopedic surgery and in dogs with acute nonspecific diarrhea (AD). Methods: Prospective cohort study of 20 dogs undergoing surgical repair of cranial cruciate ligament disease (CCL cohort) and 8 dogs with AD. Serum concentrations of cobalamin, folate, methylmalonic acid, and C-reactive protein and fecal calprotectin concentrations were measured before and 12 to 18 hours, 4 weeks, and 8 weeks after surgery in the CCL group. These biomarkers were also measured in AD dogs at initial evaluation and 4 and 8 weeks postrecovery. Results: Serum cobalamin (437 ± 186 ng/L) and folate concentrations (10.5 ± 4.8 ng/mL) at 12 to 18 hours were lower than corresponding cobalamin (630 ± 235 ng/L; P < .001) and folate concentrations (14.61 ± 6.3 ng/mL; P = .001) before surgery in CCL dogs. However, serum cobalamin (637 ± 195 ng/L) and folate concentrations (13.8 ± 5.7 ng/mL) at 4 weeks were higher than at 12 to 18 hours ( P < .001 and P = .01, respectively) and similar to baseline. All 3 AD dogs with serum cobalamin concentrations below the reference interval at baseline had serum cobalamin concentrations within the reference interval at 4 weeks. Conclusions: Major orthopedic surgery and acute nonspecific enteropathy transiently lowered serum cobalamin and folate concentrations in dogs. Clinical Relevance: Serum folate and cobalamin should be interpreted cautiously in the immediate postoperative setting or during acute gastrointestinal illness. Abnormalities should be reevaluated at a later date before pursuing other diagnostics or instituting supplementation.

Objectives: We sought to characterize cystoscopy-assisted urolith retrieval via a perineal urethrostomy stoma (CUPU) initially in a cadaveric model and then in clinical cases. We hypothesized that a CUPU would provide a reasonable alternative to the traditional approach of performing a cystotomy after perineal urethrostomy in male cats with complex or recurrent urolithiasis-associated urethral obstruction (UO). Methods: A perineal urethrostomy (PU) was performed in 20 male cat cadavers. A randomly assigned number of synthetic calculi (SynC) was placed retrograde into the urinary bladder, and an endoscopist blinded to the SynC number, performed CUPU using a flexible ureteroscope and basket retrieval device. Procedure characteristics were summarized with descriptive statistics. After completion of the cadaver phase, two male cats with naturally occurring complex or recurrent urolithiasis-associated UO that warranted PU were recruited to undergo CUPU. Clinical features and outcomes of these cases were described. Results: Four cadavers were excluded because of urethral tearing during SynC placement. A narrow urethral lumen precluded ureteroscope passage in two cadavers. In the 14 remaining cadavers, a median of 7.5 SynC (range 3–9) were placed in the urinary bladder. The CUPU median procedural time was 13.2 mins (range 6.1–24.0) and all 99 (100%) SynC were successfully retrieved from the 14 cadavers. Scope-associated tearing of the urethra or surgical site was not observed in any cadavers. Two client-owned cats with struvite urolithiasis-associated UO underwent a PU followed by CUPU. All uroliths were successfully retrieved, and periprocedural complications were not observed. Both cats had normal stoma sites 4 weeks postoperatively and neither cat had owner-reported dysuria 3 months postoperatively. Conclusions and relevance: This study highlighted that CUPU is a feasible procedure with the potential to obviate the need for abdominal surgery in some cats with cystolithiasis and urolithiasis-associated UO that warrant PU.

Background: It is unknown if glucocorticoid malabsorption contributes to the approximate 50% treatment failure rate in dogs with protein-losing enteropathy (PLE). Objective: To compare pharmacokinetics (PK) of orally administered prednisolone in dogs with PLE vs healthy controls. Animals: Fourteen dogs with well-characterized PLE and 7 control dogs. Methods: Prospective case-controlled study. Dogs were treated with 1 mg/kg prednisolone PO once daily for approximately 3 weeks. Venous blood samples were collected at set timepoints before and after prednisolone administration on the first (T1) and final (T2) study days. Total and non-protein bound serum prednisolone concentrations were determined using liquid chromatography tandem-mass spectrometry, and pharmacokinetics variables were derived from the drug concentration data. Pharmacokinetics variables were compared between PLE and control dogs and between PLE short-term responders and non-responders. Results: The PLE dogs had a shorter half-life of the terminal slope than control dogs (harmonic mean of 1.3 vs 1.8 hours; P = .05) whereas the percentage of serum prednisolone that was non-protein bound was higher in PLE dogs than in control dogs (median of 15.7% vs 6.7%; P = .02) at T1. Total prednisolone drug exposures and maximum total serum drug concentrations did not differ between PLE and control dogs at T1 or T2, nor did they differ between short-term responders and non-responders within the PLE population (P > .05 for all comparisons). Conclusions and Clinical Importance: Overall drug exposures are similar between PLE dogs and healthy controls. Glucocorticoid malabsorption is unlikely to be a common cause of treatment failure in dogs with PLE.

Background: Enteral nutrition (EN) is essential for management of hepatic lipidosis (HL) in cats. Objectives: To determine if time to start of EN and other clinicopathologic variables are associated with outcome in cats with HL. Animals: Forty-eight cats with HL. Methods: Retrospective study. Information retrieved from medical records and client communications included clinicopathologic findings, time to start of EN, initial % of resting energy requirements provided, type of feeding tube, duration of hospitalization, and 3-month survival. Variables were compared between surviving and nonsurviving cats and between cats fed ≤12 hours and >12 hours after hospital admission. Multivariable statistical testing was performed to further investigate variables of interest. Results: Seventeen of 25 (68%) cats fed ≤12 hours and 13 of 23 (57%) of cats fed >12 hours after hospital admission survived (P = .55). Only increasing age (odds ratio [OR], 1.313; 95% confidence interval [CI], 1.032-1.671; P = .03) and the presence of ascites (OR, 6.415; 95% CI, 1.354-30.395; P = .02) were associated with death in multivariable analysis. Hospitalization duration (median, interquartile range [IQR]) was shorter in cats fed >12 hours (2.8 days; IQR, 2.1-3.8 days) as compared with cats fed ≤12 hours (4.8 days; IQR, 3.6-6.2 days) after hospital admission (P < .001). Conclusions and Clinical Importance: An initial stabilization period before EN introduction does not decrease survival or increase duration of hospitalization in cats with HL.

Urine marking, aggression, and other behavioral concerns are common reasons for cat owners to seek veterinary care. Empiric treatment for lower urinary tract disease or primary behavior disorders are commonly pursued, especially in those cases with normal routine laboratory evaluations. Herein, we report the clinicopathologic findings in eight sexually altered cats that were diagnosed with androgen-secreting adrenocortical tumors. Nearly all cats (n= 7) initially were evaluated for inappropriate urination and pungent urine, with additional behavioral concerns including aggression (n= 3) and excess vocalization (n= 4) commonly reported. Penile barbs (n= 5) were identified in all five male cats, and an enlarged clitoris was observed in one female cat. Testing of serum androgen concentrations revealed abnormally high androstenedione (n= 1) or testosterone (n= 7) concentrations. In the five cases with available adrenal tissue, histopathologic evaluation identified either an adrenocortical adenoma (n= 3) or adrenocortical carcinoma (n= 2). Hormonal abnormalities resolved and clinical signs improved in the four cats that underwent surgical adrenalectomy, with each of these cats surviving >1 year. However, clinical signs were minimally impacted with medical treatments, including one cat in which trilostane treatment failed to improve clinical signs or testosterone concentrations. This collection of cases underscores the importance of a detailed physical examination as well as the consideration of endocrine disturbances in cats undergoing evaluation for inappropriate urination or aggression. Furthermore, this report adds to the growing body of evidence that sex-hormone secreting adrenal tumors in cats may be an under-recognized syndrome.

To determine if urine electrolyte assessments can be used to monitor the adequacy of mineralocorticoid therapy in dogs with hypoadrenocorticism (HA). 29 dogs with naturally occurring glucocorticoid- and mineralocorticoid-deficient HA. Urine sodium and potassium concentrations, sodium-to-potassium ratios, sodium-to-creatinine ratios, and potassium-to-creatinine (K:Cr) ratios were evaluated in dogs with newly diagnosed HA that were treated with desoxycorticosterone pivalate (DOCP). Dogs underwent measurements of urine and serum sodium, potassium, and creatinine concentrations and plasma renin activities twice monthly for up to 3 months. Regression analyses and calculation of coefficients of determination (R ²) were performed to investigate potential associations between urine and serum variables. Urine variables also were compared between dogs considered to be undertreated or overtreated based on plasma renin activities. Urine K:Cr ratios were significantly associated with serum potassium concentrations 10 to 14 days (P = .002) and 30 days (P = .027) after the initial DOCP injection, but R ² values were only 0.35 and 0.17, respectively. Urine K:Cr ratios (median [IQR]) also were higher in dogs that were overtreated with DOCP (1.3 [0.7 to 2.3]) as compared to those dogs that were undertreated with DOCP (0.8 [0.5 to 0.9]) at 10 to 14 days after the initial DOCP injection (P = .039) but not at 30 days after the initial injection. Other urine variables were not significantly different between undertreated and overtreated dogs. Measures of urine electrolytes were not useful for assessing the adequacy of mineralocorticoid therapy in HA dogs that were treated with DOCP. To determine if urine electrolyte assessments can be used to monitor the adequacy of mineralocorticoid therapy in dogs with hypoadrenocorticism (HA). 29 dogs with naturally occurring glucocorticoid- and mineralocorticoid-deficient HA. Urine sodium and potassium concentrations, sodium-to-potassium ratios, sodium-to-creatinine ratios, and potassium-to-creatinine (K:Cr) ratios were evaluated in dogs with newly diagnosed HA that were treated with desoxycorticosterone pivalate (DOCP). Dogs underwent measurements of urine and serum sodium, potassium, and creatinine concentrations and plasma renin activities twice monthly for up to 3 months. Regression analyses and calculation of coefficients of determination (R ²) were performed to investigate potential associations between urine and serum variables. Urine variables also were compared between dogs considered to be undertreated or overtreated based on plasma renin activities. Urine K:Cr ratios were significantly associated with serum potassium concentrations 10 to 14 days (P = .002) and 30 days (P = .027) after the initial DOCP injection, but R ² values were only 0.35 and 0.17, respectively. Urine K:Cr ratios (median [IQR]) also were higher in dogs that were overtreated with DOCP (1.3 [0.7 to 2.3]) as compared to those dogs that were undertreated with DOCP (0.8 [0.5 to 0.9]) at 10 to 14 days after the initial DOCP injection (P = .039) but not at 30 days after the initial injection. Other urine variables were not significantly different between undertreated and overtreated dogs. Measures of urine electrolytes were not useful for assessing the adequacy of mineralocorticoid therapy in HA dogs that were treated with DOCP.

Background: A panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders. Objectives: To evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases. Animals: Fifty-five dogs with primary intestinal disease. Methods: Serum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points. Results: Twenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P = .99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs. Conclusions and Clinical Importance: The evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.

Background: The relationship between the development of SHPT and ionized magnesium (iMg) concentrations in blood of dogs with chronic gastrointestinal (GI) disease and abnormally low 25(OH)D is undefined. Objectives: Evaluate relationships between ionized magnesium (iMg), PTH, ionized calcium (iCa), and 25(OH)D in dogs with chronic enteropathy (CE) with or without protein-losing enteropathy (PLE) and abnormal 25(OH)D. Determine whether dogs with CE or PLE, decreased 25(OH)D and SHPT have differences in iMg, iCa, or 25(OH)D when compared to dogs that do not have SHPT. Animals: Fifty dogs with CE +/− PLE and abnormally low serum 25(OH)D. Methods: Retrospective search of submissions database at a veterinary diagnostic laboratory for vitamin D profiles submitted in years 2017 to 2020. Cases were excluded if supplemented with Ca, Mg, or vitamin D. Spearman correlation was performed to evaluate relationships between iMg, PTH, 25(OH)D, and iCa. Ionized Mg, iCa, and 25(OH)D concentrations were compared between dogs with SHPT and those with normal PTH concentrations. Results: Concentrations of iMg were weakly negatively correlated with PTH (rho, −.31; P = .03), and weakly positively correlated with serum 25(OH)D (rho, .34, P = .02) and iCa (rho, .42, P = .003). Ionized magnesium concentrations were lower in dogs with abnormally low 25(OH)D and SHPT compared to dogs with abnormally low 25(OH)D and normal parathyroid hormone concentrations (P = .01). Conclusions and Clinical Importance: Hypomagnesemia might contribute to alterations in iCa and parathyroid hormone in dogs with CE +/− PLE and abnormally low 25(OH)D.