THERAPY OF ENDOCRINE DISEASE: Treatment of malignant pheochromocytoma and paraganglioma

Baudin, Éric; Habra, Mouhammed Amir; Deschamps, Frédèric; Cote, Gilbert J.; Dumont, Frédéric; Cabanillas, Maria E.; Arfi-Roufe, J.; Berdelou, A.; Moon, Bryan S.; Ghuzlan, Abir Al; Patel, Shreyaskumar; Leboulleux, Sophie; Jiménez, Camilo

doi:10.1530/eje-14-0113

Cited by 100 publications

(91 citation statements)

References 57 publications

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“…Patients with malignant PCC have a high risk of mortality and morbidity. The overall 5-year survival rate of malignant PCC is 40–77% [9–11]. Therefore, a greater understanding of the biology underlying PCC is needed in order to advance diagnostic testing and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Rowbotham

Enfield

Martínez

et al. 2014

International Journal of Endocrinology

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Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

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Section: Introductionmentioning

confidence: 99%

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Rowbotham

Enfield

Martínez

et al. 2014

International Journal of Endocrinology

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“…MRI has a higher sensitivity and specificity for staging and follow-up especially in the case of hepatic metastasis. [2], [9] Currently, the PET/CT with FDG is the study of choice for the anatomic location compared with CT and other functional studies 123I-MIBG [2], [10].…”

Section: Discussionmentioning

confidence: 99%

Metastatic pheochromocytoma to liver without elevation of metanephrines and catecholamines

López-Gómez

Salazar-Álvarez

Adame

et al. 2016

International Journal of Surgery Case Reports

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“…Because more severe forms of constipation start mildly, this finding suggests that severe constipation may be preventable. Patients with metastatic PH/PG may be at a higher risk for constipation as they are frequently treated with vincristine-based chemotherapy, antiemetics such as ondansetron, and/or narcotics to relieve pain (25,26), all of which have constipating effects. In these patients, early intervention with medications that offset the constipating effects and close evaluation of this symptom are required.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Constipation: an overlooked, unmanaged symptom of patients with pheochromocytoma and sympathetic paraganglioma

Thosani

Ayala-Ramirez

Román-Gonzaléz

et al. 2015

European Journal of Endocrinology

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Objective: Pheochromocytomas (PHs) and sympathetic paragangliomas (PGs) are tumors that produce catecholamines, predisposing patients to cardiovascular disease and gastrointestinal effects such as constipation. Objectives: i) determine the prevalence of constipation, its risk factors, and its impact on survival; ii) identify whether a systematic combination of fiber, water, and laxatives was effective for treatment of constipation. Design and methods: We retrospectively studied 396 patients with PH/PG diagnosed in 2005-2014. The study population was patients with constipation as a presenting symptom; the control group was patients without constipation as a presenting symptom. The MD Anderson Symptom Inventory was used to assess constipation and quality of life. Results: Twenty-three patients (6%) had constipation. Constipation was associated with headaches, palpitations, diaphoresis, weight loss, and excessive noradrenaline production (P!0.0001). Eighteen of these patients had non-metastatic primary tumors larger than 5 cm and/or extensive metastases. No statistically significant differences in age, sex, and genotype were noted between the study and control groups. In patients without metastases, resection of the primary tumor led to symptom disappearance. A systematic combination of fiber, water, and laxatives was associated with symptom improvement. Two patients who presented unmanaged constipation died because of sepsis from toxic megacolon. Conclusions: Constipation is a rare and potentially lethal complication in patients with PH/PGs. Severe constipation can be prevented by recognizing and treating mild symptoms.

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THERAPY OF ENDOCRINE DISEASE: Treatment of malignant pheochromocytoma and paraganglioma

Cited by 100 publications

References 57 publications

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

Metastatic pheochromocytoma to liver without elevation of metanephrines and catecholamines

Constipation: an overlooked, unmanaged symptom of patients with pheochromocytoma and sympathetic paraganglioma

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