Glucagon-Induced Pheochromocytoma Crisis

Hosseinnezhad, Alireza; Black, Robert M.; Aeddula, Narothama Reddy; Adhikari, Deep; Trivedi, Nitin

doi:10.4158/ep10388.cr

Cited by 13 publications

(5 citation statements)

References 15 publications

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“…Nevertheless, a wide variation of precipitating factors has been postulated, including physical stimulus to the tumor [ 1 ], as occurred in patient 1 of our case series who developed a PPGL crisis after fracturing his left femur at the site of a large bone metastasis. Administration of glucagon which stimulates secretion of catecholamines by the pheochromocytoma, as happened in patient 4, has also previously been described as an eliciting factor for PPGL crisis [ 16 ]. The most prevalent precipitating factor is surgical resection of the PPGL.…”

Section: Discussionmentioning

confidence: 99%

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

2021

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Pheochromocytoma/paraganglioma (PPGL)-induced catecholamine crisis is a rare endocrine emergency leading to life-threatening hemodynamic instability causing end-organ damage or dysfunction. As it is associated with a significant mortality rate of approximately 15%, recognizing the signs and symptoms and making the appropriate diagnosis are critical. For this purpose, we report the clinical course of the crisis in four out of a total of six patients with a PPGL crisis from a cohort of 199 PPGL patients of a single tertiary referral center for PPGL patients in the Netherlands diagnosed between 2002 and 2020. Successful treatment of a PPGL crisis demands prompt diagnosis, vigorous pharmacological therapy, and emergency tumor removal if the patient continues to deteriorate.

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Section: Discussionmentioning

confidence: 99%

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

2021

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“…Hypertensive crisis induced by ionic contrast material administered intra-arterially or intravenously, in patients with pheochromocytomas is a well-known phenomenon [4] [5]. Furthermore, certain agents, such as glucagon, have been reported to induce catecholamine release from pheochromocytomas with subsequent multi-organ injury during CT [6]. In patients with pheochromocytoma of the urinary bladder, an increase in intravesical pressure during micturition can also lead to catecholamine release and hypertensive symptoms [9].…”

Section: Discussionmentioning

confidence: 99%

“…Hypertensive crisis induced by intra-arterial injection of ionic contrast medium in patients with catecholamine-secreting tumors is a well-known phenomenon [4] [5]. Furthermore, certain agents, such as glucagon, have been reported to induce catecholamine release from pheochromocytomas with subsequent multi-organ injury [6]. Later studies have shown that non-ionic contrast does not have this same effect when given intravenously during CT scans [3] [6] [7].…”

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confidence: 99%

Transient Hypertensive Response to CO<sub>2</sub> Aortography in a Patient with Pheochromocytoma

Patel¹,

Cho²

2015

OJRad

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We report on a 15-year-old male with 4-year history of hypertension and retroperitoneal masses referred to Interventional Radiology to evaluate the nature of the persistent masses and renal artery stenosis. Angiographic evaluation began with CO2aortogram during which the patient had a hypertensive response with bradycardia and arrhythmia to the intra-aortic injection of CO2. His hypertension, bradycardia, and arrhythmia responded to an intravenous nitroglycerin drip without administration of alpha or beta blockers. Due to this response and neovascularity of the mass, selective venous sampling of catecholamines and renin was performed which confirmed functioning paragangliomas and hemodynamically significant stenosis of left accessory renal artery, respectively. This is the first known case of hypertensive response to CO2 aortography in a patient with unsuspected functioning paragangliomas. We propose that patients with known or suspected diagnosis of catecholamine-secreting tumors undergoing CO2 angiography should be considered for pre-procedural treatment with alpha and beta blockage or have the appropriate medication on hand with close monitoring in the event of hypertensive response.

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“…The alternative energy-generation pathway is somewhat less efficient, requiring a much larger cellular influx of glucose to maintain the energy needs in tumor cells, and the increased glucose consumption can be exploited for diagnostic purpose [64]. Provocative tests using glucagon has previously been performed in patients with undiscovered PPGLs, and these tests have been reported to lead to multi-organ failure or hypertensive emergency in some cases [65][66][67]. This, together with the low sensitivity of the glucagon test, and diverse expression of the glucagon receptor in different PCC syndromes has led to recommendations to not use this test in clinical practice [68].…”

Section: Plos Geneticsmentioning

confidence: 99%

MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression

et al. 2020

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Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B :p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A . The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors.

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Glucagon-Induced Pheochromocytoma Crisis

Cited by 13 publications

References 15 publications

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

Transient Hypertensive Response to CO<sub>2</sub> Aortography in a Patient with Pheochromocytoma

MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression

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Glucagon-Induced Pheochromocytoma Crisis

Cited by 13 publications

References 15 publications

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

Pheochromocytoma/paraganglioma crisis: case series from a tertiary referral center for pheochromocytomas and paragangliomas

Transient Hypertensive Response to CO&lt;sub&gt;2&lt;/sub&gt; Aortography in a Patient with Pheochromocytoma

MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression

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Transient Hypertensive Response to CO<sub>2</sub> Aortography in a Patient with Pheochromocytoma