Pheochromocytoma: a changing perspective and current concepts

Abstract

This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40–60% of tumors are linked to a known mutation. Tumor DNA should be sampled first. Next-generation sequencing is the best and most cost-effective choice and also helps with the expansion of current knowledge. Recent advancements have also led to the increased incorporation of regulatory RNA, metabolome markers, and the NETest in PPGL workup. PPGL presentation is highly volatile and nonspecific due to its multifactorial etiology. Symptoms mainly derive from catecholamine (CMN) excess or mass effect, primarily affecting the cardiovascular system. However, paroxysmal nature, hypertension, and the classic triad are no longer perceived as telltale signs. Identifying high-risk subjects and diagnosing patients at the correct time by using appropriate personalized methods are essential. Free plasma/urine catecholamine metabolites must be first-line examinations using liquid chromatography with tandem mass spectrometry as the gold standard analytical method. Reference intervals should be personalized according to demographics and comorbidity. The same applies to result interpretation. Threefold increase from the upper limit is highly suggestive of PPGL. Computed tomography (CT) is preferred for pheochromocytoma due to better cost-effectiveness and spatial resolution. Unenhanced attenuation of >10HU in non-contrast CT is indicative. The choice of extra-adrenal tumor imaging is based on location. Functional imaging with positron emission tomography/computed tomography and radionuclide administration improves diagnostic accuracy, especially in extra-adrenal/malignant or familial cases. Surgery is the mainstay treatment when feasible. Preoperative α-adrenergic blockade reduces surgical morbidity. Aggressive metastatic PPGL benefits from systemic chemotherapy, while milder cases can be managed with radionuclides. Short-term postoperative follow-up evaluates the adequacy of resection. Long-term follow-up assesses the risk of recurrence or metastasis. Asymptomatic carriers and their families can benefit from surveillance, with intervals depending on the specific gene mutation. Trials primarily focusing on targeted therapy and radionuclides are currently active. A multidisciplinary approach, correct timing, and personalization are key for successful PPGL management.

Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics

“…Neuroblastoma is a pediatric cancer originating from the sympathetic nervous system, often characterized by metastasis and recurrence, and is often inoperable in many instances [ 28 , 29 ]. Pheochromocytomas and paragangliomas are rare neuroendocrine tumors (NETs) associated with a relatively high incidence of local invasion or metastasis, rendering some cases unsuitable for surgical intervention [ 30 , 31 ]. Most of these tumors express high levels of NE transporters [ 28 , 32 ].…”

Adrenal Cysts: To Operate or Not to Operate?

“…Accordingly, a recent study showed that 78% of pheochromocytomas with atypical anatomical imaging features (on CT or MRI) were totally or predominantly cystic [42]. In this situation, the most accurate way to assess these lesions is using a variety of functional imaging modalities like iodine metaiodobenzylguanidine (MIBG) scintigraphy, 18 fluoro (F) deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), 18 FDG-PET/MRI, 18 F-Fluoro-dihydroxyphenylalanine ( 18 F-DOPA) PET/CT, and somatostatin receptor (SSTR) agonist-based PET/CT imaging [42,43]. It was demonstrated that even completely cystic pheochromocytomas captivate radiotracers like MIBG and FDG in the peripheral tumour rim or in residual tumour tissue [42].…”

Long-term Persistent Hypertension after Pheochromocytoma and Paraganglioma Resection: A Multi-Center Study

“…Among the clinical symptoms mentioned above, high blood pressure is the classic clinical clue for PPGL 4 . Approximately 65-80% of PPGL patients suffer from hypertension 5 . Surgical resection of PPGL combined with a preoperative combination of α-blockers is an effective treatment option for PPGL 6 .…”