Acute onset of hypertensive encephalopathy in a dog with right adrenal pheochromocytoma and neoplastic invasion of the caudal vena cava: Case report and review of the literature.

Background: Canine pheochromocytomas (PCCs) are rare tumors of the adrenal medulla. Clinical signs are often vague, resulting in intermittent catecholamine over secretion or neoplastic invasion of adjacent structures. Case Description: A 12-year-old Epagneul Breton dog with a 1-year history of chronic kidney disease, was examined for acute onset of severe neurological signs. Based on clinical and instrumental data, hypertensive encephalopathy was suspected. Cardiac and abdominal ultrasound were performed. Severe hypertensive cardiopathy and a right adrenal gland mass with invasion of the caudal vena cava were diagnosed. Computed tomography imaging confirmed the suspect of invasive malignant neoplasia. Emergency pharmacological therapy was started to reduce systemic pressure, improve clinical signs, and stabilize the dog in view of surgical resolution. After initial improvement, patient conditions abruptly worsened, and euthanasia was elected. Histology examination confirmed a right adrenal PCC, with caval invasion. Conclusion: To the authors' conclusions, acute hypertensive encephalopathy is a peculiar manifestation of PCCs. Ultrasound is a useful, and rapid test to suspect PCC as it can detect adrenal alterations, caval invasion, metastasis, and cardiac sequelae consistent with the condition. PCC can mimic multiple affections, and be misinterpreted, especially when a concurrent disease has already been diagnosed. Veterinarians need to be aware that comorbidities could mask clinical signs and delay diagnosis. Furthermore, this clinical case reminds us to include PCC also in the differential diagnosis of dogs with an acute onset of severe neurological signs.

Metabolomic profiling of pheochromocytomas in dogs: Catecholamine phenotype and tricarboxylic acid cycle metabolites.

BACKGROUND: In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). HYPOTHESIS/OBJECTIVES: To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). ANIMALS: Ten healthy dogs, 21 dogs with PCC. METHODS: Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. RESULTS: Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%-98%] vs 14% [11%-26%]; P < .001), and significantly lower tissue proportion of epinephrine (12% [1%-62%] vs 86% [74%-89%]; P < .001). Pheochromocytomas exhibited significantly lower fumarate (0.4-fold; P < .001), and malate (0.5-fold; P = .008) contents than NAs. Citrate was significantly higher in PCCs than in NAs (1.6-fold; P = .015). One dog in the PCC group had an aberrant succinate : fumarate ratio that was 25-fold higher than in the other PCCs, suggesting an SDHx mutation. CONCLUSIONS AND CLINICAL IMPORTANCE: This study reveals a distinct catecholamine content and TCA cycle metabolite profile in PCCs. Metabolite profiling might be used to uncover underlying pathogenic variants in TCA cycle genes in dogs.

Acute respiratory distress syndrome associated with a pheochromocytoma in an adult dog.

A 16-year-old castrated male shih tzu dog was brought to the emergency service because of an acute (24 h) history of gagging, coughing, and lethargy. Physical examination revealed dyspnea concurrent with diffuse, bilateral, pulmonary crackles and wheezes. Oxygen saturation, measured with a pulse oximeter, was < 95%. Thoracic radiographs revealed a multifocal alveolar pattern superimposed over a diffuse interstitial pattern with normal heart size. The dog continued to be dyspneic despite oxygen therapy. In accordance with the radiographic findings, further supportive care was recommended. Due to the unknown prognosis and financial constraints, the owner elected humane euthanasia. Necropsy confirmed a pheochromocytoma and lung changes without evidence of congestive heart failure. Findings were consistent with diffuse alveolar damage. These findings correlated with the dog's clinical diagnosis of acute respiratory distress syndrome (ARDS). No other disease processes associated with ARDS were identified. The purpose of this case report is to describe an unusual presentation of ARDS likely associated with a pheochromocytoma and confirmed by necropsy. Acute respiratory distress syndrome associated with a pheochromocytoma has been described in medical literature but has never been reported in veterinary medicine. Key clinical message: Pheochromocytomas should be added to the list of risk factors associated with ARDS in dogs. Dogs with a suspected diagnosis of pheochromocytoma whose owners elect against surgical removal should be closely monitored for an acute onset of respiratory distress, which could suggest the development of ARDS.

Syndrome de détresse respiratoire aiguë associé à un phéochromocytome chez un chien adulteUn chien shih tzu mâle castré de 16 ans a été amené aux services d'urgence en raison d'antécédents aigus (24 heures) de haut-le-coeur, de toux et de léthargie. L'examen physique a révélé une dyspnée concomitante à des crépitements et des respirations sifflantes diffuses, bilatérales et pulmonaires. La saturation en oxygène, mesurée avec un oxymètre de pouls, était < 95 %. Les radiographies thoraciques ont révélé un motif alvéolaire multifocal superposé à un motif interstitiel diffus avec une taille cardiaque normale. Le chien est resté dyspnéique malgré l'oxygénothérapie. Conformément aux résultats radiographiques, des soins de soutien supplémentaires ont été recommandés. En raison du pronostic inconnu et des contraintes financières, le propriétaire a opté pour l'euthanasie sans cruauté. La nécropsie a confirmé un phéochromocytome et des modifications pulmonaires sans signe d'insuffisance cardiaque congestive. Les résultats concordaient avec des lésions alvéolaires diffuses. Ces résultats étaient en corrélation avec le diagnostic clinique du syndrome de détresse respiratoire aiguë (ARDS) du chien. Aucun autre processus pathologique associé à l'ARDS n'a été identifié. Le but de ce rapport de cas est de décrire une présentation inhabituelle de l'ARDS probablement associée à un phéochromocytome et confirmée par la nécropsie. Le syndrome de détresse respiratoire aiguë associé à un phéochromocytome a été décrit dans la littérature médicale mais n'a jamais été rapporté en médecine vétérinaire.Message clinique clé:Les phéochromocytomes doivent être ajoutés à la liste des facteurs de risque associés à l'ARDS chez le chien. Les chiens avec un diagnostic suspecté de phéochromocytome dont les propriétaires choisissent de ne pas procéder à l'ablation chirurgicale doivent être étroitement surveillés pour détecter l'apparition aiguë d'une détresse respiratoire, ce qui pourrait suggérer le développement d'un ARDS.(Traduit par Dr Serge Messier).

Anesthetic management of a dog undergoing unilateral adrenalectomy for phaeochromocytoma excision using a partial intravenous anesthetic protocol.

Background: The anesthetic management of adrenalectomies for phaeochromocytoma excision, a catecholamine-secreting tumor, is challenging due to the potential for fatal complications following severe hemodynamic variations, including hypertensive crisis following tumor manipulation or sympathetic stimulation, but also severe hypotension and volume depletion post resection. Case Description: An 11 kg, 15-year-old male neutered Jack Russel Terrier, with mitral valve disease stage B2, was referred for adrenalectomy for phaeochromocytoma resection. The patient was administered per os prazosin 0.11 mg/kg twice a day and amlodipine 0.125 mg/kg once a day for preoperative stabilization. On the day of surgery, the dog received maropitant 1 mg/kg intravenously (IV) and was premedicated with 0.2 mg/kg methadone IV. Anesthesia was induced with alfaxalone 1 mg/kg IV and midazolam 0.2 mg/kg IV and maintained with partial intravenous anesthesia using sevoflurane in 70% oxygen and constant rate infusions of dexmedetomidine 0.5 µg/kg/hour and maropitant 100 µg/kg/hour. After induction of anesthesia, the dog was mechanically ventilated, and a transversus abdominal plane block was performed with ropivacaine 0.2%. The dog remained remarkably stable with a single, self-limiting, hypertension episode recorded intraoperatively. Postoperative rescue analgesia consisted of methadone and ketamine. The dog was discharged 48 hours after surgery, but persistent hypertension was reported at suture removal. Conclusion: The use of a low-dose dexmedetomidine CRI, a maropitant CRI, and a transversus abdominal plane block provided stable perioperative hemodynamic conditions for phaeochromocytoma excision in a dog.

Imaging guided adrenalectomy with Indocyanine green fluorescence in a dog with a pheochromocytoma.

IMPORTANCE: This case report presents the successful surgical removal of a pheochromocytoma in a dog using indocyanine green (ICG) fluorescence imaging. CASE PRESENTATION: A 10-year-old, 6.87 kg, spayed female poodle was referred for an abdominal mass and eight episodes of vomiting. Computed tomography revealed masses in the spleen and left adrenal gland. Based on the plasma normetanephrine levels, the patient was diagnosed with pheochromocytoma. Subsequently, a total splenectomy and left adrenalectomy were performed. A dose of 5 mg/kg ICG was administered intravenously 24 h prior to surgery. Using ICG allowed visualization of tumor margins, aiding in complete resection and minimizing anesthesia-related risks. CONCLUSIONS AND RELEVANCE: No evidence of recurrence or metastasis has been observed for 12 months. To our knowledge, this is the first report of the surgical removal of a pheochromocytoma using intraoperative ICG imaging in veterinary medicine. This case highlights the efficacy of ICG fluorescence imaging as a valuable tool for the surgical management of adrenal tumors in veterinary medicine.

Hypercoagulability based on thromboelastography is common in dogs undergoing adrenalectomy.

OBJECTIVE: Thromboelastography (TEG) is a whole blood assay that yields global assessment of hemostasis, as it evaluates clot time, strength, and kinematics of clot formation and lysis. The main objective was to describe preoperative TEG findings in dogs that had an adrenalectomy performed and, secondarily, to describe TEG findings in the dogs with or without hyperadrenocorticism (HAC). ANIMALS: 30 dogs that had preoperative TEG and adrenalectomy performed. METHODS: Medical records between 2018 and 2022 were reviewed. Signalment, diagnostic data, and perioperative treatment were abstracted. RESULTS: 53% (16/30) of the dogs were hypercoagulable, and none were hypocoagulable. Based on histopathology, 6 of 9 dogs with adenocarcinoma were hypercoagulable, 4 of 8 with pheochromocytoma were hypercoagulable, and 6 of 10 with adenoma were hypercoagulable. None of the 3 dogs with other histopathologic diagnoses or combinations of diagnoses (adrenocortical hyperplasia, poorly differentiated sarcoma, and both adrenocortical adenocarcinoma and pheochromocytoma) were hypercoagulable. Of the 14 dogs tested preoperatively for HAC, 4 of 8 HAC dogs were hypercoagulable and 2 of 6 non-HAC dogs were hypercoagulable. CLINICAL RELEVANCE: The present report describes for the first time TEG findings for dogs undergoing adrenalectomy and suggests that the majority of dogs with adrenal neoplasia are hypercoagulable based on TEG results.

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.

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.

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.

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.