New biology of pheochromocytoma and paraganglioma

Elsevier

Available online 21 September 2022

Endocrine PracticeHighlights•

All pheochromocytomas and paragangliomas are now considered to have metastatic potential and therefore, their categorization into benign and malignant should be omitted.

Recent studies found the following clinical features are significantly different between patients with and without these tumors: tachycardia, lower body mass index, pallor, sweating, palpitations, tremor, and nausea.

Plasma metanephrines yield slightly better diagnostic sensitivity and should be preferred in patients at a high risk (e.g. those with an adrenal tumor) of having pheochromocytoma or paraganglioma over urinary free metanephrines. Age-specific upper reference limits should be used to improve diagnostic accuracy of biochemical testing.

All patients with identified mutations or hereditary syndromes should receive tumor periodic surveillance for which they are most likely predisposed. Furthermore, genetic testing should be performed in individuals with positive family history, especially those symptoms and signs related to catecholamine excess.

Cluster 1 tumors are well localized by 68Ga-DOTATATE PET/CT, while cluster 2 tumors are localized by 18F-fluorodopa PET/CT and 123I-MIBG scintigraphy. Since 68Ga-DOTATATE is widely available this imaging modality has the highest sensitivity compared to other functional modalities. 68Ga-DOTATATE is also recommended for post-surgical follow-up imaging to rule out any remaining or recurrent tumor(s).

In rapidly growing tumors, chemotherapy (usually using CVD) is the approach of choice. Other options include tyrosine kinase inhibitors and temozolomide with or without capecitabine. In slowly or moderately growing metastatic lesions targeted radionuclide therapies are recommended.

Abstract

Pheochromocytomas and paragangliomas continue to be defined by significant morbidity and mortality despite their many recent advances in diagnosis, localization, and management. These adverse outcomes are largely related to mass effect as well as catecholamine-induced hypertension, tachyarrhythmias and consequent target organ damage, acute coronary syndromes, and strokes (ischemic and hemorrhagic stroke). Thus, a proper understanding of the physiology and pathophysiology of these tumors and recent advances are essential to affording optimal care. These major developments largely include a re-definition of metastatic behavior, a novel clinical categorization of these tumors into three genetic clusters, and an enhanced understanding of catecholamine metabolism and consequent specific biochemical phenotypes. Current advances in imaging of these tumors, are shifting the paradigm from poorly specific anatomic modalities to more precise characterization of these tumors utilizing the advent and development of functional imaging modalities. Furthermore, recent advances have revealed new molecular events in these tumors that are linked to their genetic landscape and therefore provide new therapeutic platforms. A few of these prospective therapies translated into new clinical trials, especially for patients with metastatic or inoperable tumors. Finally, outcomes are ever-improving as patients are cared for at centers with cumulative experience and well-established multidisciplinary tumor boards. In parallel these centers have supported national and international collaborative efforts and world-wide clinical trials. These concerted efforts have led to improved guidelines collaboratively developed by health care professionals with a growing expertise in these tumors and consequently improving detection, prevention, and identification of genetic susceptibility genes in these patients.

Keywords

Pheochromocytoma

paraganglioma

catecholamine

metanephrine

genetics

imaging

positron emission tomography

therapy

review

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© 2022 Published by Elsevier Inc. on behalf of the AACE.

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