Update in Management of Pheochromocytoma and Paraganglioma

Akiyo TanabeJapan Speaker Update in Management of Pheochromocytoma and ParagangliomaPheochromocytoma and paraganglioma (PPGL) are rare endocrine neoplasms. Because it is difficult to predict the future development of metastasis based on biochemical testing or pathological findings, all PPGLs were reclassified as malignant tumors with metastatic potential in the revised 2017 WHO Classification of Endocrine Tumors. In Japan, the clinical practice guidelines for PPGL were revised in 2025. The diagnosis of PPGL requires the presence of tumors with characteristic findings. A definitive diagnosis is made based on elevated serum and urinary metanephrine fractions, positive tumor 123I-MIBG scintigraphy, and pathological findings in surgical cases. Measurement of plasma or urinary catecholamine fractions is no longer recommended because of its limited diagnostic accuracy; instead, measurement of plasma or urinary metanephrine fractions, which are metabolites of catecholamines, is currently recommended. Imaging modalities include computed tomography (CT), magnetic resonance imaging (MRI), and 123I-MIBG scintigraphy; however, 68Ga-DOTATATE positron emission tomography, which offers higher specificity and superior spatial resolution, is increasingly being used as an alternative to 123I-MIBG scintigraphy. The first-line treatment is tumor resection, regardless of whether metastasis is present or not. In patients at high surgical risk, catecholamine synthesis inhibitors (metyrosine) may be administered preoperatively in combination with α-adrenergic blockers. Because there is no clearly established effective therapy for metastatic disease, multidisciplinary management is required, combining debulking surgery to control catecholamine excess, systemic therapies such as CVD chemotherapy, 131I-MIBG therapy, and somatostatin receptor radionuclide therapy, as well as local treatments including external beam radiotherapy and transarterial embolization. Although tyrosine kinase inhibitors and immune checkpoint inhibitors have been investigated, their therapeutic efficacy remains limited. Even in patients with metastatic disease, active surveillance without immediate treatment —so-called watch and wait— may be a reasonable option for those with slow tumor growth, well-controlled catecholamine-related symptoms, and a low risk of local organ damage, with active treatment initiated upon evidence of disease progression. Pathogenic variants in PPGL-associated genes are identified in approximately 20–40% of patients, and variant-specific diagnostic and therapeutic algorithms are increasingly being proposed.