Hypercalcemia associated with blastomycosis in dogs

Hypercalcemia that could not be explained by previously recognized causes was detected in 4 dogs with systemic blastomycosis. A variety of malignancies and certain endocrine, metabolic, and renal disorders may cause hypercalcemia, but to our knowledge, no infectious diseases have been associated with hypercalcemia in dogs. Increased production of calcitriol by mononuclear cells was thought to be the mechanism of hypercalcemia in granulomatous disease.     

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.     

Evaluation of total and ionized calcium status in dogs with blastomycosis: 38 cases (1997-2006)

OBJECTIVE: To determine blood ionized calcium (iCa) and serum total calcium (tCa) concentrations in dogs with blastomycosis and to evaluate whether serum tCa concentration, albumin-adjusted serum calcium concentration (AdjCa-Alb), and total protein-adjusted serum calcium concentration (AdjCa-TP) accurately predict iCa status. DESIGN: Retrospective case series. ANIMALS: 38 client-owned dogs with a cytologic diagnosis of blastomycosis. PROCEDURES: Dogs were classified as hypocalcemic, normocalcemic, or hypercalcemic on the basis of blood iCa concentration, serum tCa concentration, AdjCa-Alb, and AdjCa-TP; classification on the basis of serum tCa concentration, AdjCa-Alb, and AdjCa-TP was compared with blood iCa concentration. RESULTS: Except for 2 hypercalcemic dogs, all dogs had blood iCa concentrations within the reference interval. Use of serum tCa concentration overestimated hypocalcemia in 57.9% (22/38) of dogs and underestimated hypercalcemia in 1 dog. Use of AdjCa-Alb correctly reclassified all dogs as normocalcemic that were classified as hypocalcemic on the basis of serum tCa concentration, but failed to predict hypercalcemia in 1 dog. Use of AdjCa-TP correctly reclassified all but 2 dogs as normocalcemic that were classified as hypocalcemic on the basis of serum tCa concentration, and failed to predict hypercalcemia in 1 dog. No correlation was found between blood iCa concentration and serum concentrations of tCa, total protein, and albumin; AdjCa-Alb; or AdjCa-TP. CONCLUSIONS AND CLINICAL RELEVANCE: High blood iCa concentration was uncommon in dogs with blastomycosis. Hypoalbuminemia contributed to a low serum tCa concentration despite a blood iCa concentration within reference limits. The use of serum tCa concentration, AdjCa-Alb, and AdjCa-TP may fail to identify a small number of dogs with high blood iCa concentrations.     

Calcinosis cutis associated with systemic blastomycosis in three dogs.

Three dogs treated for systemic blastomycosis with intravenous amphotericin B (one case) or amphotericin B lipid complex (two cases) developed mild to severe calcinosis cutis two to six weeks after the initiation of treatment. Abnormalities in serum calcium and phosphorus during treatment for blastomycosis or at the time of diagnosis of calcinosis cutis were slight or absent. The calcification was not associated with lesions of cutaneous blastomycosis. Calcification was limited to the skin in two cases and may have also involved the kidneys in one. The calcinosis cutis resolved completely in all three dogs with no (two cases) or only palliative (one case) therapy.     

Paraneoplastic hypercalcemia in a dog with thyroid carcinoma

This case report describes a dog with thyroid carcinoma and paraneoplastic hypercalcemia. Following thyroidectomy the dog became hypocalcemic and required supplementation with calcitriol and calcium carbonate. During the following 2 years, attempts to reduce the supplementation resulted in hypocalcemia. The dog died from renal failure with no evidence of thyroid carcinoma.     

Idiopathic hypercalcemia in cats

Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity. and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats.     

Serum parathyroid hormone-related protein concentration in a dog with a thymoma and persistent hypercalcemia

A thymoma was tentatively diagnosed by radiographic and cytologic examination in a dog with hypercalcemia and elevated serum parathyroid hormone-related protein (PTHrP) concentration. Following surgical excision, the diagnosis of thymoma was confirmed via histopathologic examination, the hypercalcemia resolved, and the PTHrP concentration decreased to below detectable limits.     

Hypercalcemia due to latrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat.

A 9-year-old, spayed female domestic shorthair cat presented for polyphagia, polydipsia, and polyuria following chronic methylprednisolone acetate therapy for pruritus. Initial diagnostics were consistent with uncomplicated diabetes mellitus. Serum calcium was within reference range. Within 12 hours the cat developed depression, anorexia, vomiting, and severe dehydration. Laboratory analysis indicated marked hypercalcemia as measured by both ionized and total calcium concentration. No underlying neoplastic or inflammatory process was identified. An adrenocorticotropic hormone stimulation test was indicative of adrenocortical insufficiency. The hypercalcemia resolved with glucocorticoid supplementation and correction of the dehydration. The diabetes mellitus and adrenal insufficiency both resolved within 9 weeks.     

Utility of diagnostic tests for and medical treatment of pulmonary blastomycosis in dogs: 125 cases (1989-2006)

OBJECTIVE: To compare results of the most common diagnostic tests for pulmonary blastomycosis in dogs, identify factors associated with outcome, and determine response to various antifungal treatment protocols. DESIGN: Retrospective case series. ANIMALS: 125 dogs with pulmonary blastomycosis. PROCEDURES: Medical records were reviewed, and information was obtained regarding diagnostic methods, results of routine laboratory testing, and radiographic response to antifungal treatment. RESULTS: 79 dogs survived, 38 died, and 8 were euthanized. Transthoracic fine-needle aspiration and transtracheal lavage were the most common diagnostic methods. Results of an agar gel immunodiffusion test for antibodies against Blastomyces dermatitidis were negative in 12 of 24 (50%) dogs. Only 3 of 94 (3.2%) dogs in which cytologic or histologic examination or bacterial culture of pulmonary samples were performed had any evidence of concurrent bacterial infection. The half-time for radiographic resolution of pulmonary infiltrates did not vary significantly with antifungal treatment, and use of a loading dosage of itraconazole was not associated with significant improvements in outcome or time to disease resolution. Dogs that died had a higher number of band neutrophils at initial examination, compared with those that survived. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the agar gel immunodiffusion test should not be used as the sole diagnostic test for pulmonary blastomycosis in dogs, that concurrent bacterial pneumonia was uncommon in dogs with pulmonary blastomycosis, and that the rate with which pulmonary infiltrates resolved did not vary significantly among antifungal treatments.     

Antigen and antibody testing for the diagnosis of blastomycosis in dogs

BACKGROUND: Early diagnosis and treatment are associated with an improved prognosis in blastomycosis. The diagnosis of blastomycosis may be missed by cytology, histopathology, culture, or serology. An enzyme immunoassay (EIA) for detection of Blastomyces dermatitidis galactomannan antigen in body fluids has been used for rapid diagnosis of blastomycosis in humans. HYPOTHESIS: Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs. METHODS: Serum and urine samples from 46 dogs with confirmed blastomycosis were tested for Blastomyces antigen and serum was tested for anti-Blastomyces antibodies. RESULTS: The sensitivity for the detection of antigen in urine was 93.5% and it was 87.0% in serum. The sensitivity of antibody detection by agar gel immunodiffusion (AGID) was 17.4% and it was 76.1% by EIA. Antigen and antibody decreased during itraconazole treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.     

Blastomycosis in nondomestic felids.

Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.     

Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog.

Megaesophagus, hypercalcemia, and eosinophilia associated with glucocorticoid deficiency were detected in a 5-year-old neutered female Standard Poodle with concurrent hypothyroidism. Clinical and biochemical abnormalities resolved with glucocorticoid replacement treatment, and the dog was normal 29 months after diagnosis. The dog's breed and sex and the existence of a second endocrinopathy supported an underlying immunologic disorder.     

Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases.

Five cats that presented for signs of lower urinary tract disease (i.e., pollakiuria and hematuria) secondary to a calcium oxalate urolithiasis are presented. On evaluation, all five cats had elevations of both serum ionized as well as total serum calcium. The hypercalcemia resolved after discontinuation of urinary acidifying therapy or a dietary change, or both.     

Evaluation of risk factors for blastomycosis in dogs: 857 cases (1980-1990)

An epidemiologic study was conducted by use of the Veterinary Medical Data Base to investigate risk factors for blastomycosis in dogs. From January 1980 through June 1990, 971 cases of blastomycosis in dogs from 22 North American veterinary teaching hospitals were identified. Of these cases, 114 (11.7%) were excluded from the study because of incomplete information regarding age, body weight, sex, and neuter status. A control group of 417,079 dogs was selected that included all other dogs with medical conditions unrelated to blastomycosis for which records were submitted to the data base during the same period. The prevalence of blastomycosis in dogs was 205/100,000 admissions during the study period. When veterinary teaching hospitals were grouped on the basis of their general geographic location, dogs in the East South central, East North central, West South central, and South Atlantic regions had a significantly (P < 0.05) increased risk of acquiring blastomycosis, compared with that of dogs in the Mountain/Pacific region. When teaching hospitals from all geographic regions were considered, dogs had a significantly (P < 0.05) increased risk of acquiring blastomycosis in autumn, compared with that in spring. Sporting dogs and hounds, as defined by the American Kennel Club, were at increased risk for blastomycosis. At highest risk were Bluetick Coonhounds, Treeing-walker Coonhounds, Pointers, and Weimaraners, compared with mixed-breed dogs. Ages of dogs with blastomycosis tended to be normally distributed. Generally, the highest-risk group was composed of sexually intact male dogs, 2 to 4 years old, weighing 22.7 to 34.1 kg. This same pattern was observed for sporting dogs and hounds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional metastatic parathyroid adenocarcinoma in a dog

A 12-year-old dachshund dog was presented for persistent hypercalcemia and hyperparathyroidism despite bilateral parathyroidectomy. Magnetic resonance imaging of the head, neck, and cranial mediastinum identified an increased number of cranial mediastinal lymph nodes with heterogeneous signal intensity. Hypercalcemia and hyperparathyroidism resolved after surgery to remove multiple cranial mediastinal lymph nodes, one of which contained presumed metastatic parathyroid tissue.     

Evaluation of the agar-gel immunodiffusion test in the diagnosis of canine blastomycosis

The agar-gel immunodiffusion test was used to evaluated 35 dogs with histopathologically confirmed blastomycosis and 98 dogs without blastomycosis. The test had a sensitivity of 91% and a specificity of 96%. Thirteen of the dogs treated for blastomycosis were tested at 6 to 33 months after treatment with amphotericin B. Ten of 13 dogs became seronegative and 3, though clinically normal, remained seropositive at 19, 20, and 20 months, respectively, after amphotericin treatment.     

Primary hyperparathyroidism in a dog.

A 6-year-old male Standard Poodle had hypercalcemia, hypophosphatemia, and a urinary concentrating defect. A parathyroid adenoma involving the left caudal parathyroid gland was surgically removed. Transient hypocalcemia followed, which resolved without treatment. A renal biopsy did not demonstrate renal parenchymal mineral deposition. Urinary concentrating ability returned after surgery.     

Blastomyces dermatitidis prostatic and testicular infection in eight dogs (1992-2005)

This was a retrospective case study of eight dogs diagnosed with prostatic or testicular B. dermatitidis infection. Signalment, clinical presentation, diagnostic procedures, and treatment options were evaluated. Review of medical records of dogs diagnosed with blastomycosis at the University of Illinois Veterinary Teaching Hospital from 1992 to 2005 yielded four dogs with prostatic blastomycosis (PB) and four dogs with testicular blastomycosis (TB). Three of the four dogs with PB and all four dogs with TB had evidence of urogenital disease. Three dogs with PB had an elevated body temperature and all had systemic disease. All dogs with TB had a normal body temperature, and three had systemic disease and one had clinical signs limited to testicular disease. Cytology or histopathology was used to diagnose PB or TB. Treatment included itraconazole or fluconazole with or without nonsteroidal anti-inflammatory drugs. PB and TB are infrequently recognized and may be under diagnosed due to failure to specifically evaluate these tissues. PB or TB should be considered in the evaluation and staging of male dogs with blastomycosis. Male dogs with urogenital signs should be evaluated via prostatic or testicular cytology or histopathology since proper identification and management of PB or TB may improve overall treatment success.     

Canine antibody response to Blastomyces dermatitidis WI-1 antigen

OBJECTIVE: To assess whether dogs with blastomycosis produce antibodies against the WI-1 and A-antigens of Blastomyces dermatitidis and whether the antibodies are useful in serodiagnosis. SAMPLE POPULATION: 359 serum samples obtained from 245 dogs. PROCEDURE: 233 samples from 122 dogs with blastomycosis, and 1 sample each from 24 dogs with suspected blastomycosis, 51 control dogs without infection, and 48 healthy dogs from an enzootic region were obtained. Antibodies against WI-1 antigen were detected by radioimmunoassay (RIA). Serum samples were tested in parallel for antibodies against the A-antigen of B dermatitidis by commercial agar-gel immunodiffusion (AGID) in a reference laboratory. RESULTS: Antibodies were detected in 92% of infected dogs by RIA and in 41 % by AGID. For 29 serum samples that were obtained 11 to 1,545 days after diagnosis, antibodies were detected in 92% of samples by RIA and 7% by AGID. For 93 serial serum samples from 29 dogs with blastomycosis, the mean anti-WI-1 titer was 1:18,761 at the time of diagnosis, and decreased to a mean of 1:1,338 by 210 days after treatment was initiated. Of 24 dogs with suspected infection, antibodies were detected in 67% by RIA and 33% by AGID. Control dogs without blastomycosis had no detectable antibodies in either assay. Thus, sensitivity was 92% for RIA and 41 % for AGID, and specificity was 100% for both tests. CONCLUSIONS AND CLINICAL RELEVANCE: Anti-WI-1 antibodies are readily detected by RIA in dogs with blastomycosis. Titers become high, decline during treatment, and persist for months. Anti-A antibodies are sometimes detected with AGID, but these decrease quickly.     

1,25‐Dihydroxyvitamin D3 and its analogues increase catalase at the mRNA,protein and activity level in a canine transitional carcinoma cell line

Antioxidant enzymes, such as catalase, superoxide dismutases (SOD), MnSOD and Cu/ZnSOD, protect cells by scavenging reactive oxygen species (ROS). Numerous studies have reported the anti‐cancer effects of 1,25‐dihydroxyvitamin D₃ (calcitriol) and its related analogues, seocalcitol and analogue V. In this study, canine bladder transitional cell carcinoma (cbTCC) cells were used to determine effects of calcitriol and its related analogues on antioxidant enzyme gene expression, protein expression and activity. Catalase mRNA was increased in response to calcitriol (10^?7 M), and seocalcitol (10^?7 and 10^?9 M). MnSOD mRNA was decreased in response to calcitriol at 10^?7 M. Catalase was significantly increased in response to calcitriol (10^?7 and 10^?9 M), and seocalcitol (10^?9 M). Catalase enzymatic activity increased in response to calcitriol, seocalcitol and analogue V (10^?9 M). In addition, global gene expression analysis identified the involvement of mitogen‐activated protein kinase (MAPK) signalling in cbTCC's response to calcitriol and seocalcitol treatment.