Adrenalectomy for the treatment of hypotension in a cat with phaeochromocytoma associated with caudal vena cava syndrome.

An 11-year-old spayed female, Persian cat was referred to the Jeonbuk Animal Medical Center for evaluation of a 2-month history of lethargy and anorexia. Physical examination revealed tachycardia and hypotension. Abdominal imaging via sonography and CT identified a right adrenal gland mass causing severe deviation and compression of the caudal vena cava. After stabilising the blood pressure and heart rate through positive inotropes and fluid therapy, right adrenalectomy was performed. Surgery confirmed the adrenal gland mass was severely compressing the caudal vena cava. Histopathological examination revealed that the mass was a pheochromocytoma. After adrenalectomy, blood pressure and heart rate stabilised and remained unaffected 8 months postsurgery. This report describes a rare case of an adrenal pheochromocytoma leading to caudal vena cava compression in a cat presenting with hypotension.

MicroRNA-194-5p/Heparin-binding EGF-like growth factor signaling mediates dexamethasone-induced activation of pseudorabies virus in rat pheochromocytoma cells.

Pseudorabies virus (PRV) is a neurotropic virus, which infects a wide range of mammals. The activity of PRV is gradually suppressed in hosts that have tolerated the primary infection. Increased glucocorticoid levels resulting from stressful stimuli overcome repression of PRV activity. However, the host cell mechanism involved in the activation processes under stressful conditions remains unclear. In this study, infection of rat PC-12 pheochromocytoma cells with neuronal properties using PRV at a multiplicity of infection (MOI) = 1 for 24 h made the activity of PRV be the relatively repressed state, and then incubation with 0.5 µM of the corticosteroid dexamethasone (DEX) for 4 h overcomes the relative repression of PRV activity. RNA-seq deep sequencing and bioinformatics analyses revealed different microRNA and mRNA profiles of PC-12 cells with/without PRV and/or DEX treatment. qRT-PCR and western blot analyses confirmed the negative regulatory relationship of miRNA-194-5p and its target heparin-binding EGF-like growth factor (Hbegf); a dual-luciferase reporter assay revealed that Hbegf is directly targeted by miRNA-194-5p. Further, miRNA-194-5p mock transfection contributed to PRV activation, Hbegf was downregulated in DEX-treated PRV infection cells, and Hbegf overexpression contributed to returning activated PRV to the repression state. Moreover, miRNA-194-5p overexpression resulted in reduced levels of HBEGF, c-JUN, and p-EGFR, whereas Hbegf overexpression suppressed the reduction caused by miRNA-194-5p overexpression. Overall, this study is the first to report that changes in the miR-194-5p-HBEGF/EGFR pathway in neurons are involved in DEX-induced activation of PRV, laying a foundation for the clinical prevention of stress-induced PRV activation.

Successful treatment of acute respiratory failure following hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma.

Background: Acute respiratory failure has been reported as one of the manifestations of hypertensive crisis in pheochromocytoma in human medicine. In dogs, no reports have been described as acute respiratory failure following hypertensive crisis. Here, we report the clinical presentation, course, and treatment of acute respiratory failure following the hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma. Case Description: A 12-year-old neutered male toy poodle was referred for the diagnostic evaluation of a right adrenal gland mass. The dog suddenly exhibited severe dyspnea with abnormal hypertension (systolic blood pressure >200 mmHg) 15 minutes after recovery from the anesthesia for the computed tomography (CT) examination. Pulmonary CT and ultrasonography findings suggested acute onset of severe pulmonary edema. Pulmonary edema was treated with mechanical ventilation (pressure-support ventilation with continuous positive airway pressure) and negative fluid balance after the administration of furosemide. Weaning from mechanical ventilation was successful 24 hours after the onset of respiratory failure. Finally, the dog was discharged 3 days after weaning from ventilation without complications. Conclusion: This report outlines a case of acute respiratory failure following a hypertensive crisis requiring mechanical ventilatory management in a dog. The onset and progression of pulmonary edema were extremely rapid. However, improvement in pulmonary edema was also rapid. Hemodynamic stability, in addition to prompt diagnosis and aggressive therapeutic intervention, including mechanical ventilation, may have contributed to the good prognosis of pulmonary edema following hypertensive crisis in a dog, which we attribute to a catecholamine storm.

Risk factors influencing death prior to discharge in 302 dogs undergoing unilateral adrenalectomy for treatment of primary adrenal gland tumours.

Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.

Phaeochromocytoma associated with cardiomyopathy and leukocytoclastic vasculitis in a dog.

Phaeochromocytomas are rare tumours of the adrenal medulla that can be associated with various presentations. Many of the better characterized clinical signs, including weakness, tachycardia and tachypnoea, are attributable to excessive and unregulated catecholamine secretion from functional tumours. In addition to catecholamine-induced cardiomyopathy and vasospasm, the invasive nature of phaeochromocytomas can lead to occlusion of the caudal vena cava contributing to systemic cardiovascular compromise. In humans, leukocytoclastic vasculitis is a rarely reported manifestation of catecholamine excess associated with phaeochromocytomas. We now describe a dog that had an invasive unilateral phaeochromocytoma with histological evidence of myocardial damage, consistent with catecholamine-induced cardiomyopathy, and leukocytoclastic vasculitis of small vessels in a range of tissues. We conclude that catecholamine excess may have played a role in the pathogenesis of vasculitis in this case. To the best of our knowledge, this is the first documented association between phaeochromocytoma and leukocytoclastic vasculitis in a non-human species.

Contrast-enhanced ultrasound features of adrenal lesions in dogs.

BACKGROUND: The contrast-enhanced ultrasound (CEUS) features of adrenal lesions are poorly reported in veterinary literature. METHODS: Qualitative and quantitative B-mode ultrasound and CEUS features of 186 benign (adenoma) and malignant (adenocarcinoma and pheochromocytoma) adrenal lesions were evaluated. RESULTS: Adenocarcinomas (n = 72) and pheochromocytomas (n = 32) had mixed echogenicity with B-mode, and a non-homogeneous aspect with a diffused or peripheral enhancement pattern, hypoperfused areas, intralesional microcirculation and non-homogeneous wash-out with CEUS. Adenomas (n = 82) had mixed echogenicity, isoechogenicity or hypoechogenicity with B-mode, and a homogeneous or non-homogeneous aspect with a diffused enhancement pattern, hypoperfused areas, intralesional microcirculation and homogeneous wash-out with CEUS. With CEUS, a non-homogeneous aspect and the presence of hypoperfused areas and intralesional microcirculation can be used to distinguish between malignant (adenocarcinoma and pheochromocytoma) and benign (adenoma) adrenal lesions. LIMITATIONS: Lesions were characterised only by means of cytology. CONCLUSIONS: CEUS examination is a valuable tool for distinction between benign and malignant adrenal lesions and can potentially differentiate pheochromocytomas from adenocarcinomas and adenomas. However, cytology and histology are necessary to obtain the final diagnosis.

Pathological Aspects and Immunohistochemical Evaluation of Troponin C in the Cardiovascular System of Dogs With Pheochromocytoma.

Functional pheochromocytomas secrete catecholamines and have been associated with cardiovascular lesions in dogs. This study aimed to describe the postmortem pathological findings in the cardiovascular system of dogs with pheochromocytoma and to evaluate the expression of cardiac troponin C in these dogs using immunohistochemical analysis. Twelve cases were identified, with a mean age of 10.6 years. The heart of all dogs was enlarged and with concentric hypertrophy of the left ventricular myocardium. Histological analysis showed cardiomyocyte necrosis and degeneration in the myocardium, with frequent bands of contraction, fibrosis, inflammation, and thickening of the medium-caliber arteries in the myocardium. There was a marked decrease or absence of immunolabeling in necrotic cardiomyocytes. We conclude that IHC for troponin C can be a useful tool for detecting myocardial necrosis in dogs with pheochromocytomas, including early cases of necrosis with only incipient cardiac changes where overt histologic abnormalities are not immediately apparent in the cardiomyocytes.

Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma.

BACKGROUND: Pheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats. OBJECTIVES: We evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC-MS-MS). METHODS: Urine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at -80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs-to-creatinine ratios. RESULTS: The PL-MN and PL-NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U-MN/Creat and U-NMN/Creat ratios were 70 and 139 µg/g, respectively. The PheoCat had a PL-MN of 3.68 nmol/L, PL-NMN of 66.27 nmol/L, U-MN/Creat of 179 µg/g, and U-NMN/Creat of 1262 µg/g. The PheoCat had markedly increased concentrations of both PL and U MNs when compared to the healthy cats. No significant difference was found between U MNs measured in urine samples that underwent 24 hours of refrigeration in comparison to those that were frozen immediately. CONCLUSIONS: We report preliminary reference intervals for PL and U MNs in cats using LC-MS-MS and the potential clinical applicability of these biomarkers for the diagnosis of PCC in cats.

Diagnosis, treatment and outcome of pheochromocytoma in a cat.

Pheochromocytoma in cats is a rare clinical condition characterised by the development of a secretory endocrine tumour that arises from the adrenal medulla. An 8-year-old castrated male, domestic shorthair cat was referred for further investigation of a 4-month history of progressive weight loss with normal appetite, polyuria/polydipsia, generalised weakness, and severe hypertension. Sonography and computed tomography of the abdomen disclosed a mass arising from the left adrenal gland. The contralateral adrenal gland was normal in size and shape. Results from a low dose dexamethasone suppression test and measurements of plasma aldosterone concentration and plasma renin activity ruled out a cortisol-secreting tumour and aldosteronoma. The clinical presentation made a sex-steroid secreting tumour unlikely. Increased plasma metanephrine and normetanephrine concentrations prioritised the differential diagnosis of pheochromocytoma. The cat underwent adrenalectomy of the left gland and histopathological diagnosis with immunohistochemical markers confirmed the diagnosis.

Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd-Chiari-like syndrome.

BACKGROUND: Surgical resection is the treatment of choice for canine adrenal pheochromocytomas (PHEOs). Information on en bloc resection of adrenal PHEO with tumour thrombus, right hepatic division and segmental caudal vena cava (CVC) running through the adrenal tumour and right hepatic division is limited. OBJECTIVE: To describe the preemptively planned en bloc resection of an extensive right adrenal PHEO involving the right hepatic division, the caval thrombus and the segmental CVC in a dog with Budd-Chiari-like syndrome (BCLS). METHODS: A 13-year-old castrated male miniature dachshund was referred for surgical treatment due to anorexia, lethargy and severe abdominal distension caused by abundant ascites. Preoperative computed tomography (CT) revealed a large mass in the right adrenal gland with a large caval thrombus obstructing the CVC and hepatic veins, which caused BCLS. Additionally, collateral vessels were formed between the CVC and azygos veins. No findings suggested obvious metastases. Based on CT findings, an en bloc resection of the adrenal tumour with caval thrombus, right hepatic division and segmental CVC was planned. RESULTS: The preoperatively planned resection was feasible; the tumour was completely resected grossly. The operation time and total Pringle manoeuvre time were 162 min and 16 min 56 s, respectively. There was no postoperative hindlimb oedema, renal dysfunction, ascites or abdominal distention. The patient's clinical signs, including appetite, fully improved. Hospitalization lasted 16 days. However, the patient died on the 130th postoperative day due to suspected metastases and cachexia. CONCLUSIONS: Even in case of an extensive infiltration of adrenal PHEO causing BCLS, an en bloc resection might be successfully achieved based on the preoperative CT findings speculating the collateral vessels formed for caudal venous return.

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma.

BACKGROUND: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). HYPOTHESIS/OBJECTIVES: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). ANIMALS: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. METHODS: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. RESULTS: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). CONCLUSIONS AND CLINICAL IMPORTANCE: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.

Stereotactic body radiation therapy as an alternative to adrenalectomy for the treatment of pheochromocytomas in 8 dogs.

The objective of this report is to describe the use and outcome of stereotactic body radiation therapy (SBRT) for treatment of pheochromocytomas in 8 dogs. Pheochromocytomas are an uncommon but challenging tumour to manage. Adrenalectomy is the standard of care for treatment of pheochromocytomas in both animals and humans; however, unpredictable catecholamine secretion from the tumour and vascular and local invasion of the tumour and thrombi can pose life-threatening perioperative and anaesthetic risks. SBRT has been investigated as an alternative to adrenalectomy in human patients with pheochromocytomas. Eight dogs with clinical signs, an adrenal mass, and cytology and/or urine normetanephrine/creatinine ratios consistent with pheochromocytoma were treated with SBRT in lieu of adrenalectomy. Three dogs presented with acute hemoabdomen. Seven dogs had caval tumour invasion, 3 with extension into the right atrium. Following SBRT, all dogs had complete resolution of clinical signs and reduced urine normetanephrine/creatinine ratio and/or tumour size. No significant anaesthetic complications were encountered. Acute radiation toxicity was limited to grade I gastrointestinal signs in 3 dogs and resolved within 1-2 days of symptomatic therapy. Five of 8 dogs were alive at the time of follow up, with a median follow up time of 25.8 months. SBRT resulted in a favourable outcome and mitigated the life-threatening risks of adrenalectomy in these 8 dogs. SBRT may be a safe and effective alternative to adrenalectomy for pheochromocytomas in dogs with non-resectable tumours, or for owners averse to the risks of surgery.

Differential Expression of Secretogranins II and III in Canine Adrenal Chromaffin Cells and Pheochromocytomas.

Secretogranin II (SgII) and III (SgIII) function within peptide hormone-producing cells and are involved in secretory granule formation. However, their function in active amine-producing cells is not fully understood. In this study, we analyzed the expression profiles of SgII and SgIII in canine adrenal medulla and pheochromocytomas by immunohistochemical staining. In normal adrenal tissues, the intensity of coexpression of these two secretogranins (Sgs) differed from each chromaffin cell, although a complete match was not observed. The coexpression of vesicular monoamine transporter 2 (VMAT2) with SgIII was similar to that with chromogranin A, but there was a subpopulation of VMAT2-expressing cells that were negative or hardly detectable for SgII. These results are the first to indicate that there are distinct expression patterns for SgII and SgIII in adrenal chromaffin cells. Furthermore, the expression of these two Sgs varied in intensity among pheochromocytomas and did not necessarily correlate with clinical plasma catecholamine levels in patients. However, compared with SgIII, the expression of SgII was shown to be strong at the single-cell level in some tumor tissues. These findings provide a fundamental understanding of the expression differences between SgII and SgIII in normal adrenal chromaffin cells and pheochromocytomas.

Metastatic Canine Phaeochromocytoma with Unusual Manifestation.

We report the clinical, pathological and immunohistochemical characteristics of a phaeochromocytoma (PCC) in a 9-year-old male neutered Golden Retriever dog. The dog presented with acute onset of deteriorating cervical pain but was otherwise normal on general physical and neurological examinations. Magnetic resonance imaging of the cervical spine revealed a focal, extramedullary, infiltrative, poorly demarcated, heterogeneous mass with moderate contrast enhancement at the left cranial articular process of C2, associated with osteolysis and pathological fractures of C2, and marked soft tissue trauma. Due to the severe lesions and grave prognosis, the dog was euthanized. Post-mortem examination revealed severe enlargement of the right adrenal gland due to a neoplasm of the adrenal medulla. C2 was lytic and there was a white, well-demarcated, firm neoplastic mass in the surrounding musculature. Neoplasms were also present in, and adjacent to, the prostate gland and in pulmonary lymph nodes. Histologically, the neoplasms were composed of dense sheets and nests of small, round to polyhedral cells with frequent palisading along fine connective tissue septa, karyomegaly, multinucleated cells and frequent mitotic figures. Immunohistochemically, neoplastic cells expressed chromogranin A and synaptophysin. Gross, microscopic and immunohistochemical findings support the diagnosis of PCC, originating from the right adrenal gland, with multiple metastases in the cervical spine, prostate gland and pulmonary lymph nodes. This case highlights the difficulty of intra-vitam diagnosis of PCC as its manifestation can be highly variable. PCC should be considered as a rare but possible differential diagnosis for painful vertebral masses in elderly dogs.

Prediction of vascular invasion using a 7-point scale computed tomography grading system in adrenal tumors in dogs.

BACKGROUND: Previous studies evaluating the accuracy of computed tomography (CT) in detecting caudal vena cava (CVC) invasion by adrenal tumors (AT) used a binary system and did not evaluate for other vessels. OBJECTIVE: Test a 7-point scale CT grading system for accuracy in predicting vascular invasion and for repeatability among radiologists. Build a decision tree based on CT criteria to predict tumor type. METHODS: Retrospective observational cross-sectional case study. Abdominal CT studies were analyzed by 3 radiologists using a 7-point CT grading scale for vascular invasion and by 1 radiologist for CT features of AT. ANIMALS: Dogs with AT that underwent adrenalectomy and had pre- and postcontrast CT. RESULTS: Ninety-one dogs; 45 adrenocortical carcinomas (50%), 36 pheochromocytomas (40%), 9 adrenocortical adenomas (10%) and 1 unknown tumor. Carcinoma and pheochromocytoma differed in pre- and postcontrast attenuation, contralateral adrenal size, tumor thrombus short- and long-axis, and tumor and thrombus mineralization. A decision tree was built based on these differences. Adenoma and malignant tumors differed in contour irregularity. Probability of vascular invasion was dependent on CT grading scale, and a large equivocal zone existed between 3 and 6 scores, lowering CT accuracy to detect vascular invasion. Radiologists' agreement for detecting abnormalities (evaluated by chance-corrected weighted kappa statistics) was excellent for CVC and good to moderate for other vessels. The quality of postcontrast CT study had a negative impact on radiologists' performance and agreement. CONCLUSIONS AND CLINICAL IMPORTANCE: Features of CT may help radiologists predict AT type and provide probabilistic information on vascular invasion.

Short- and long-term survival after adrenalectomy in 53 dogs with pheochromocytomas with or without alpha-blocker therapy.

OBJECTIVE: To report data related to the short- and long-term survival of dogs undergoing adrenalectomy for pheochromocytoma, and to determine the influence of preoperative alpha-blocker therapy. STUDY DESIGN: Retrospective. ANIMALS: Fifty-three dogs. METHODS: Medical records were reviewed for dogs diagnosed with pheochromocytoma and treated with adrenalectomy between 2010 and 2020. Preoperative management, imaging studies, intraoperative cardiovascular instability, complications, and procedural information were recorded. When applicable, duration of survival and cause of death, time to recurrence or metastasis, and postoperative complications were recorded. RESULTS: During anesthesia, a hypertensive episode was documented in 46/53 dogs and arrhythmias were recorded in 16/53 dogs. Of these, 37/46 hypertensive dogs and 11/16 dogs with arrhythmias were treated with an alpha-blocker before surgery. Intraoperative systolic blood pressures reached higher levels by a magnitude of nearly 20% in dogs that were treated preoperatively with an alpha-blocker (P = .01). All dogs survived surgery and 44 survived to discharge. Follow up ranged from 6 to 1653 days (median 450 days). Median survival time for dogs discharged from the hospital was 1169 days (3.2 years). Recurrence and metastasis were suspected in 3 and 8 dogs, respectively. CONCLUSION: Most dogs survived the immediate postoperative period and achieved long-term survival with a low reported incidence of tumor recurrence or metastasis. Preoperative alpha-blocker therapy was not associated with increased survival. CLINICAL SIGNIFICANCE: The favorable outcomes reported in this study should be taken into consideration when discussing treatment options for dogs with pheochromocytomas. This study provides no evidence to support preoperative alpha-blocker therapy.

Update on Adrenalectomy.

Surgical removal is the standard of care for adrenal tumors greater than 2.0 cm diameter. For tumors smaller than 2.0 cm, imaging techniques evaluating patterns of contrast washout may offer a promising avenue for early identification of adrenal malignancy. Pretreatment of pheochromocytoma with phenoxybenzamine is associated with reduced surgical mortality risk. Surgical technique can be laparoscopic or open, depending on tumor anatomy and the experience of the surgeon. Vascular invasion is a contraindication for a laparoscopic technique. This review provides a summary of minimally invasive and open adrenalectomy techniques, including a discussion of management of vascular invasion and partial cavectomy.

Effective treatment with mitotane for a canine case of presumed ectopic Cushing's syndrome-related pheochromocytoma.

Background: In humans, ectopic Cushing's syndrome (ECS) is characterized by hypercortisolemia, which is caused by small lung carcinoma, bronchial carcinoids, and pheochromocytoma. In dogs, only a few cases of ECS associated with pheochromocytoma have been reported to date. Case Description: Herein, we describe a canine case of malignant pheochromocytoma that is presumed to be the cause of ECS. An 11-year-old, castrated, male Toy Poodle with hypercortisolemia was diagnosed with an adrenal tumor (AT) and treated with mitotane. Although repeated adrenocorticotropic hormone stimulation tests revealed improvement in the dog's condition by mitotane treatment, its condition started declining 197 days post-diagnosis, and he died on day 280. The necropsy revealed the AT was a pheochromocytoma, not an adrenocortical tumor. However, because of no pathological change in the pituitary gland and the other adrenal gland, pheochromocytoma was presumed to be the cause of ECS. Conclusion: This is the first report that describes the effectiveness of mitotane against presumed ECS-related pheochromocytoma.

Autoresuscitation and pheochromocytoma multisystem crisis in a dog.

OBJECTIVE: To describe the clinical course of a dog with a pheochromocytoma multisystem crisis that exhibited autoresuscitation after cardiac arrest. CASE SUMMARY: An approximately 10-year-old male neutered terrier mix dog presented for collapse. Abdominal imaging was suggestive of a pheochromocytoma, and clinical pathology data and thoracic imaging suggested the presence of a multisystem crisis. The dog developed cardiopulmonary arrest that was followed by autoresuscitation. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first report of autoresuscitation in a dog. The phenomenon may have been associated with a pheochromocytoma multisystem crisis.

Urinary vanillylmandelic acid:creatinine ratio in dogs with pheochromocytoma.

Pheochromocytoma diagnosis in dogs is challenging because biochemical tests are not always available. In humans, urinary vanillylmandelic acid (VMA) is part of a pheochromocytoma biochemical diagnostic profile, whereas its diagnostic accuracy is currently unknown in dogs with pheochromocytoma. Prospectively, VMA was determined by HPLC and expressed as the ratio with respect to urinary creatinine (VMA:C). The diagnostic accuracy of the VMA:C ratio was evaluated by analyzing the receiver operating characteristic (ROC) curve in 10 healthy dogs, 8 dogs with pituitary-dependent hypercortisolism, 8 dogs with adrenal-dependent hypercortisolism, and 7 dogs with pheochromocytoma. The pheochromocytoma diagnosis was confirmed by histology and immunohistochemistry in all tumors. The VMA:C ratio was significantly higher in dogs with pheochromocytoma (158 [53.4 to 230.8] × 10-3) than in dogs with adrenal-dependent hypercortisolism (48.1 [24.3 to 144.9] × 10-3; P < 0.05), dogs with pituitary-dependent hypercortisolism (37.5 [32 to 47.1] × 10-3; P < 0.001), and healthy dogs (33.8 [13.3 to 87.9] × 10-3; P < 0.001). When using a VMA:C ratio >58.2 × 10-3 for pheochromocytoma diagnosis, a sensitivity of 85.7% and a specificity of 88.4% were obtained. Nevertheless, when using a cut-off ratio of 4 times the median VMA:C ratio determined in healthy dogs, there was no overlap (100% specificity). The area under the ROC curve indicated that the VMA:C ratio test could be used to discriminate between dogs with and without pheochromocytoma, what leads to the conclusion that it is useful for pheochromocytoma diagnosis in dogs.