UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: 3P association (3PA) is a rare condition with co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma. There have been less than a hundred documented cases of 3PA, which can be sporadic or related to genetic mutations. The present case report describes the first Iranian patient with 3PA and a 90th case of 3PA in the available literature.
UNASSIGNED: A 36-year-old Caucasian male was admitted with headache and sudden increase in blood pressure. An abdominal CT scan revealed a retroperitoneal mass posterior to the inferior vena cava, later removed and diagnosed as a pheochromocytoma. Four years later, he noticed occasional mild headaches and a painless mass on the right side of his neck. The ultrasonography evaluations suggested a carotid body tumor, which was surgically removed. About a month after his second surgery, the severity of the patient\'s headaches worsened, and he developed right homonymous hemianopia. A brain MRI showed a mass in favor of macroadenoma, craniopharyngioma, or meningioma, and elevated prolactin level led to the diagnosis of macroprolactinoma.
METHODS: Based on the provided history, this patient was diagnosed with 3PA, and a genetic study identified a positive succinate-dehydrogenase-complex subunit b mutation, possibly linked to his family history of carotid body tumor.
RESULTS: He has remained symptom-free during his visits every 3 months.
CONCLUSIONS: The number of cases diagnosed with 3PA worldwide is increasing. Using clinical and genetic assessments, we can timely diagnose and adequately monitor individuals with or at risk of 3PA.

OBJECTIVE: This white paper provides practical guidance for clinicians encountering bilateral adrenal masses.
METHODS: A case-based approach to the evaluation and management of bilateral adrenal masses. Specific clinical scenarios presented here include cases of bilateral adrenal adenomas, hemorrhage, pheochromocytomas, metastatic disease, myelolipomas, as well as primary bilateral macronodular adrenal hyperplasia.
RESULTS: Bilateral adrenal masses represent approximately 10% to 20% of incidentally discovered adrenal masses. The general approach to the evaluation and management of bilateral adrenal masses follows the same protocol as the evaluation of unilateral adrenal masses, determined based on the patient\'s clinical history and examination as well as the imaging characteristics of each lesion, whether the lesions could represent a malignancy, demonstrate hormone excess, or possibly represent a familial syndrome. Furthermore, there are features unique to bilateral adrenal masses that must be considered, including the differential diagnosis, the evaluation, and the management depending on the etiology. Therefore, considerations for the optimal imaging modality, treatment (medical vs surgical therapy), and surveillance are included. These recommendations were developed through careful examination of existing published studies as well as expert clinical opinion consensus.
CONCLUSIONS: The evaluation and management of bilateral adrenal masses require a comprehensive systematic approach which includes the assessment and interpretation of the patient\'s clinical history, physical examination, dynamic hormone evaluation, and imaging modalities to determine the key radiographic features of each adrenal nodule. In addition, familial syndromes should be considered. Any final treatment options and approaches should always be considered individually.

Diffuse alveolar hemorrhage (DAH) can be caused by various conditions, categorized as autoimmune and non-autoimmune. Immunofactor-mediated vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, and antiphospholipid antibody syndrome, are common autoimmune causes. Non-autoimmune factors include infectious or toxic exposures and neoplastic conditions. The diagnosis of DAH, resulting from excessive catecholamine release from an adrenal pheochromocytoma or extra-adrenal paraganglioma, can present diagnostic challenges and necessitate prompt treatment. In this report, we present a case of pheochromocytoma that manifested as an adrenal incidentaloma (diagnosed during the management of sudden-onset DAH after cholecystectomy). Case report: A 39-year-old female patient with adrenal incidentaloma developed DAH following a cholecystectomy procedure, presenting with sudden-onset hemoptysis and dyspnea. Administration of glucocorticoids, known to precipitate pheochromocytoma crisis (PCC), was required before the cause was determined. Intubation and mechanical ventilation were necessary due to persistent hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). The patient in this case experienced two epidoses of PCC while she was on mechanical ventilation. Subsequent work-up revealed a 26 × 25 mm left adrenal adenoma with hormonal confirmation of catecholamine hypersecretion. A laparoscopic adrenalectomy was done eight months later to excise the left adrenal gland. Subsequent examination of the tissue revealed pheochromocytoma, thereby validating the initial diagnosis. Conclusion: Adrenal incidentalomas may be pheochromocytomas (adrenal incidentalomas can manifest as pheochromocytomas), even without adrenergic symptoms. It is recommended that adrenal incidentalomas undergo evaluation for pheochromocytoma before undergoing invasive surgery or receiving corticosteroid treatment. When considering potential causes of DAH without further elucidation, including a pheochromocytoma or paraganglioma (PPGLs) in the differential diagnosis is important.

UNASSIGNED: Pheochromocytoma-induced takotsubo syndrome (Pheo-TTS) significantly increases the risk of adverse events for inpatient. The early identification of risk factors at admission is crucial for effective risk stratification and minimizing complications in Pheo-TTS patients.
UNASSIGNED: We conducted a systematic review combined with hierarchical cluster and feature importance analysis of demographic, clinical and laboratory data upon admission, alongside in-hospital complication data for Pheo-TTS patients. We analyzed cases published in PubMed and Embase from 2 May 2006 to 27 April 2023.
UNASSIGNED: Among 172 Pheo-TTS patients, cluster analysis identified two distinct groups: a chest pain dominant (CPD) group (n = 86) and a non-chest pain dominant (non-CPD) group (n = 86). The non-CPD group was characterized by a younger age (44.0 ± 15.2 vs. 52.4 ± 14.4, p < 0.001), a higher prevalence of neurological/psychiatric disorders (53.5% vs. 32.6%), and increased presentation of dyspnea (87.2% vs. 17.4%), pulmonary rales (59.3% vs. 8.1%), and tachycardia (77.9% vs. 30.2%). Additionally, they exhibited more atypical takotsubo syndrome (TTS) imaging phenotypes (55.8% vs. 36.5%, all p < 0.05). The non-CPD group experienced more than a 2-fold increase for in-hospital adverse events compared to the CPD group (70.9% vs. 30.2%, p < 0.001). After adjusting for confounding factors, the absence of chest pain (odds ratio [OR] = 0.407, 95% confidence interval [CI] 0.169-0.979, p = 0.045), the presence of abdominal symptoms (OR = 3.939, 95% CI 1.770-8.766, p = 0.001), pulmonary rales (OR = 4.348, 95% CI 1.857-10.179, p = 0.001), and atypical TTS imaging phenotype (OR = 3.397, 95% CI 1.534-7.525, p = 0.003) remained as independent predictors of in-hospital complications.
UNASSIGNED: Clinical manifestations and imaging features at admission help to predict in-hospital complications for Pheo-TTS patients.

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

Pheochromocytoma (PCC) surgery presents significant challenges due to the hemodynamic instability induced by catecholamine release. Effective perioperative management is essential to minimize complications and ensure optimal outcomes. This comprehensive review examines the role of esmolol, a short-acting beta-blocker, in hemodynamic stabilization during PCC surgery. We provide an overview of the pathophysiology of PCC, highlighting the cardiovascular effects of excessive catecholamines. Challenges in perioperative management and the need for effective hemodynamic control are discussed. The pharmacology and mechanisms of action of esmolol are outlined, along with evidence from clinical studies supporting its use in PCC surgery. Comparative analyses with other hemodynamic agents are presented, along with recommendations for optimizing esmolol administration and monitoring. Key findings include the ability of esmolol to attenuate catecholamine-induced hypertension and tachycardia, thereby promoting hemodynamic stability and reducing the risk of intraoperative cardiovascular crises. Implications for clinical practice include the incorporation of esmolol into perioperative management protocols and the importance of multidisciplinary collaboration. Future research directions include further elucidating optimal dosing regimens, comparative effectiveness studies, and exploring novel therapeutic approaches. Collaboration among clinicians, researchers, and pharmaceutical companies is essential to advance the care of patients undergoing surgery for PCC.

BACKGROUND: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap.
METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP).
RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery.
CONCLUSIONS: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient\'s follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.

This case report highlights a 47-year-old woman with an adrenal incidentaloma and a history of polysubstance abuse, finally diagnosed with pheochromocytoma. Characterized by episodic hypertension, headaches, and palpitations, pheochromocytoma is a rare condition with potential complications like uncontrolled hypertension and heart failure. Remarkably, during her 28-day hospitalization, continuous monitoring revealed no instances of tachycardia or arrhythmias despite multiple symptomatic episodes. This finding aligns with reports that while 50-70% of symptomatic pheochromocytoma patients experience palpitations, only about 20% exhibit detectable tachycardia or arrhythmias. This discrepancy suggests varied individual cardiovascular responses to catecholamine surges, possibly due to differences in catecholamine inactivation rates and receptor sensitivity. This case underscores the complexity of pheochromocytoma symptoms and highlights the need for personalized diagnostic and management strategies. Furthermore, it points to a significant gap in understanding the correlation between palpitations and arrhythmia in pheochromocytoma, indicating a critical area for future research.