Serum 17-alpha-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism

OBJECTIVE: To assess serum 17-alpha-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism. DESIGN: Prospective study. ANIMALS: 16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism. PROCEDURE: ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia. RESULTS: In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration.     

Pituitary–adrenal axis function in dogs with neoplasia*

Adrenocorticotropic hormone (ACTH) stimulation tests were done in healthy and tumour‐bearing dogs. In the tumour‐bearing dogs, plasma endogenous ACTH (eACTH) concentration was measured and adrenal gland size was assessed ultrasonographically. Measurements in the tumour‐bearing dogs were taken prior to therapy. No difference existed in basal or ACTH‐stimulated cortisol concentration between tumour‐bearing and healthy dogs. No difference existed in eACTH concentration between dogs with non‐haematopoietic neoplasia (NHN) and lymphoma. However, of 20 dogs with lymphoma, 15% had increased basal serum cortisol concentration, 5% had an exaggerated response to ACTH and 5% had an increased eACTH concentration. Of 15 dogs with NHN, 20% had increased basal cortisol concentration, 7% had an exaggerated ACTH response and no dogs had an increased eACTH concentration. Of the dogs with lymphoma and NHN, 5 and 13%, respectively, had decreased basal cortisol concentrations; 20% of dogs with lymphoma and 13% with NHN had a subnormal ACTH response. eACTH levels were below the reference range in 10% of dogs with lymphoma and 7% with NHN. Overall, 10 adrenal glands were enlarged in seven dogs, five with lymphoma and two with NHN. The clinical significance of these findings remains to be determined.     

Cranial vena caval syndrome secondary to transvenous pacemaker implantation in two dogs

Superior vena caval syndrome is a rare, but reported complication of transvenous pacemaker implantation in humans. This syndrome can occur secondary to fibrotic and/or thrombotic obstruction of venous blood flow into the right atrium. The therapeutic approach depends on the suspicion of the presence of an active thrombus and may include antithrombotics, angioplasty and/or surgical venoplasty. We describe two dogs that developed severe pleural effusion secondary to stricture formation in the cranial vena cava 4 years after dual chamber transvenous pacemaker implantation. The stenosis was most likely due to fibrosis secondary to the transvenous pacemaker leads. Balloon angioplasty of the lesion resulted in resolution of the pleural effusion in both patients. Balloon angioplasty appears to be a viable therapeutic approach in dogs with cranial vena caval syndrome caused by focal stenotic lesions.     

Adrenalectomy and caval thrombectomy in a cat with primary hyperaldosteronism

A 13-year-old, castrated male, domestic longhaired cat was diagnosed with primary hyperaldosteronism from an adrenal gland tumor and a thrombus in the caudal vena cava. Clinical signs included cervical ventriflexion, lethargy, weakness, inappetence, and diarrhea. Laboratory tests revealed hypokalemia, normonatremia, hyperglycemia, hypophosphatemia, and elevated creatine kinase activity. Hypokalemia worsened despite oral potassium supplementation. An adrenalectomy and caval thrombectomy were successfully performed utilizing deliberate hypothermia followed by progressive rewarming.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Ultrasonographic identification of vascular invasion by adrenal tumors in dogs

Adrenalectomy is the treatment of choice for adrenal tumors that are producing adverse clinical signs. Surgical planning prior to adrenalectomy is aided by identifying tumors with invasion into adjacent vessels or the presence of a tumor thrombus extending into the caudal vena cava. In this paper, we evaluated the sensitivity and specificity of ultrasound in determining if vascular invasion or tumor thrombus is present. Thirty-four dogs with 36 adrenal tumors were reviewed retrospectively. Overall, 36% of tumors had vascular invasion. Abdominal ultrasound was 100% sensitive and 96% specific in identifying the presence of a tumor thrombus in the caudal vena cava. The sensitivity and specificity was 76% and 96%, respectively, when all forms of vascular invasion were evaluated and included patients with vascular wall invasion without concurrent thrombus. Abdominal ultrasound is a good screening tool for identifying vascular invasion or tumor thrombus associated with adrenal tumors in dogs.     

Hyperlipasemia in 6 dogs with pancreatic or hepatic neoplasia: evidence for tumor lipase production

Abstract: A marked increase in serum pancreatic lipase (PL) activity with minimal concurrent increase in serum α-amylase activity was observed in 6 dogs with pancreatic or hepatic neoplasia. Serum PL activity ranged from 5410 U/L to 42,900 U/L, 11 to 93 times the upper reference limit for our laboratory. Neoplasms included pancreatic adenocarcinoma (n=3), endocrine carcinoma (n=2), and hepatic carcinoma of unknown origin (n=1). Tumor tissue and normal canine pancreatic tissue were stained histochemically with diastase periodic acid-Schiff to demonstrate zymogen granule content, and immunohistochemically with human monoclonal antibody for PL. Normal canine pancreatic tissue stained positive for both zymogen granule content and PL. Five of the 6 tumors stained positive for zymogen granule content, and 2 of the 6 tumors stained positive for PL. Together, the his-tochemical and immunohistochemical staining patterns suggested tumor PL production in 5 of the 6 dogs. Marked, unexplained hyperlipasemia may be a noninvasive indicator and biochemical marker for neoplasia of the pancreas and liver in dogs.     

Blastomycosis granuloma involving the cranial vena cava associated with chylothorax and cranial vena caval syndrome in a dog

A four-year-old, sexually intact, male dachshund was diagnosed with pulmonary blastomycosis. Itraconazole was administered for 60 days, and the dog was considered to be disease-free at three- and 12-month reevaluations. Two years following discontinuation of itraconazole, the dog developed a granuloma of the cranial vena cava resulting in chylothorax and cranial vena caval obstruction. To the authors' knowledge, this is the first case of a blastomycotic granuloma involving the vena cava reported in the dog. Blastomycosis should be considered as a differential diagnosis for both chylothorax and cranial vena caval syndrome in the dog.     

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)     

Caudal vena cava kinking in dogs with ascites

A 9-year-old dog with spontaneous ascites was found to have hepatic vein distension and a tortuous vena cava on abdominal ultrasound. In right lateral recumbency, the caudal vena cava crossed the diaphragm and became kinked before entering into the right atrium. Following this observation, we performed an experimental study in a normal dog to determine whether kinking of the caudal vena cava could be the result and not the cause of ascites. Ascites was induced using warm saline injected through a needle inserted into the abdominal cavity. Venograms were collected from different body positions, under four conditions: before and after a total of one, two and 3 liters of saline had been injected. Caudal vena cava kinking was observed in the experimental dog after 2 liters of fluid had been injected. Vena cava obstruction may cause ascites, but we found that sometimes caudal vena cava kinking can be the result and not the cause of the peritoneal effusion.     

Relative adrenal insufficiency in dogs with sepsis

BACKGROUND: A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. HYPOTHESIS: That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. ANIMALS: Thirty-three septic dogs admitted to a small animal intensive care unit. METHODS: Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. RESULTS: Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE: Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.     

Cardiopulmonary function values before and after heartworm removal in dogs with caval syndrome

Cardiopulmonary function values were determined before and after surgical removal of adult heartworms in 25 dogs with spontaneous and 4 dogs with drug-induced caval syndrome (CS). Fifteen dogs with spontaneous CS (recovery group) and 4 dogs with drug-induced CS (drug-induced CS group) recovered after removal, and 10 dogs with spontaneous CS were euthanatized or died (nonsurviving group). Before heartworm removal, injected radiographic contrast medium was regurgitated from the right ventricle to the right atrium. Mean pulmonary arterial pressure and total pulmonary resistance were not statistically different between the recovery and nonsurviving groups of dogs, but the end-diastolic right ventricular pressure (mean +/- SD, 6.9 +/- 9.1 mm of Hg) and the a (8.7 +/- 9.2 mm of Hg)- and v (6.3 +/- 8.5 mm of Hg)-waves of the right atrial pressure curve in the recovery group were less, respectively, than the end-diastolic right ventricular pressure (17.3 +/- 6.0 mm of Hg) and the a (15.8 +/- 6.1 mm of Hg)- and v (21.4 +/- 6.9 mm of Hg)-waves in dogs of the nonsurviving group. After heartworm removal, contrast medium regurgitation disappeared, and cardiac output of the right ventricle increased in dogs of the recovery (from 2.08 +/- 0.72 to 2.38 +/- 0.68 L/min; P less than 0.05) and drug-induced CS (from 1.42 +/- 0.19 to 1.88 +/- 0.26 L/min, P less than 0.05) groups. However, regurgitation remained, and cardiac output did not increase in some dogs of the nonsurviving group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathologic fracture in dogs with suspected or confirmed osteosarcoma

Objective: To evaluate clinical presentation of pathologic fractures associated with suspected or confirmed osteosarcoma in dogs and to assess treatment and survival times. Study design: Case series. Animals: Dogs (n=25) appendicular pathologic fracture. Methods: Medical records (January 1997–May 2008) of dogs with pathologic fracture associated with a suspected or confirmed osteosarcoma were reviewed. Dogs were included if they had radiographic evidence of a pathologic fracture and a presumptive or definitive diagnosis of osteosarcoma. Radiographic details, histopathology, and/or cytology findings were recorded. Overall median survival time (MST) and MST of treated dogs were calculated. Age, sex, breed, and other concurrent treatment were evaluated. Results: Rottweilers, Irish Wolfhounds, and Greyhounds were the most common breeds represented. Most dogs had minor trauma and 60% had lameness preceding the fracture. Most commonly, fractures were nondisplaced with minimal comminution. None of the dogs had radiographic evidence of pulmonary metastases at admission. Immediate (13 dogs; 52%) and delayed (4; 16%) euthanasia were performed. One dog was not treated and died 90 days after diagnosis. Three dogs (12%) were treated by amputation alone, 1 (4%) with amputation and chemotherapy, and 3 (12%) with internal fixation using an interlocking nail. Overall MST was 1 day (range, 0–623 days) and MST of treated dogs was 406.5 days. Histologic confirmation of osteosarcoma was available in all treated dogs and 6 euthanatized dogs. Conclusions: Treatment of pathologic fracture associated with presumptive osteosarcoma should be considered as an option to amputation or euthanasia if owners desire other options.     

Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia

The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy^® in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted.     

Changes in C-reactive protein and haptoglobin in dogs with lymphatic neoplasia

Acute phase proteins (APP) are regarded as a useful diagnostic tool in humans with lymphomas, leukaemias and multiple myeloma. C-reactive protein (CRP) and haptoglobin concentrations were measured in dogs with malignant multicentric (high grade) lymphoma (n=16), acute lymphoblastic leukaemia (ALL) (n=11), chronic lymphocytic leukaemia (CLL) (n=7) and multiple myeloma (n=8). Twenty-five healthy dogs served as controls. Measurements of the CRP plasma concentration were performed using a commercial ELISA and haptoglobin was measured with an assay based on its haemoglobin binding capacity. Global group comparisons using Kruskal-Wallis-test revealed significant group differences for both APPs (P<0.0001). Median CRP concentrations were increased in all groups with neoplastic lymphatic disorders (lymphoma: 37.2mg/L, ALL: 47.8mg/L, CLL: 35.5mg/L, myeloma: 17.6mg/L) compared to controls (1.67mg/L; P<0.001). Compared to the healthy controls (median=0.59g/L), haptoglobin was especially increased in dogs with ALL (6.8g/L, P<0.0001) followed by dogs with malignant lymphoma (3.8g/L, P<0.0001), CLL (3.2g/L, P=0.0008), and multiple myeloma (3.0g/L, P=0.0163). For both APPs, a wide range of values was found in all patient groups. The results indicate that particularly severe and acute lymphatic neoplasia, such as high grade lymphoma and ALL, cause significant acute phase reactions in dogs and must be included in the differential diagnoses of increased blood levels of these APPs.