Hereditary pheochromocytoma is associated with pathogenic variants in the RET and VHL genes and is inherited in an autosomal dominant pattern, meaning a single altered copy of either gene is sufficient to significantly increase the risk of tumor development. Each child of an affected individual has a 50% chance of inheriting the variant. RET is also associated with multiple endocrine neoplasia syndromes, while VHL variants are linked to von Hippel-Lindau disease, both of which may include pheochromocytoma as a component. Not every individual who carries a pathogenic variant will develop pheochromocytoma, as penetrance is variable. Genetic counseling is recommended for individuals and families to understand inheritance risks and testing implications.

Diagnosis of pheochromocytoma involves a combination of biochemical testing and imaging, with genetic testing playing a central role in hereditary cases. Elevated urinary and plasma catecholamine levels, including norepinephrine and its metabolites, provide biochemical evidence of a catecholamine-secreting tumor. A positive regitine blocking test may also support the diagnosis. Imaging of the adrenal glands is used to localize the tumor. For individuals with a known or suspected hereditary predisposition, molecular genetic testing identifying pathogenic variants in RET or VHL confirms the underlying cause. Because many of these features can occur in other conditions, genetic and biochemical testing together are essential to confirm the diagnosis and guide management.

Management of pheochromocytoma typically involves surgical removal of the tumor, with careful preoperative preparation to control blood pressure and prevent dangerous catecholamine surges. Two FDA-approved treatments are available to support management: iobenguane I-123 (AdreView), used for imaging to detect and localize the tumor, and metyrosine (Demser), which inhibits catecholamine synthesis and may be used to reduce hormone levels before or when surgery is not possible. Ongoing monitoring for tumor recurrence or the development of additional tumors is an important component of long-term care, particularly for individuals with hereditary forms. A multidisciplinary team including endocrinology and surgery specialists is typically involved. Patients should discuss treatment options with their healthcare team to determine which therapies are appropriate for their specific situation.

Outcomes for individuals with pheochromocytoma vary depending on whether the tumor is benign or malignant, whether it is sporadic or part of a hereditary syndrome, and how promptly it is diagnosed and treated. With timely surgical intervention, many individuals experience significant improvement in blood pressure and resolution of symptoms. Individuals with hereditary forms related to RET or VHL variants may face an increased risk of recurrent or additional tumors over time, requiring long-term surveillance. The course is highly variable, and outcomes depend on individual factors including tumor characteristics, extent of disease, and access to specialized care. Regular follow-up with an experienced care team is an important part of long-term management.

Pheochromocytoma is an active area of investigation, with numerous ongoing clinical trials evaluating new diagnostic approaches, systemic therapies, and treatment strategies for advanced or hereditary forms of the condition. Research efforts include studies of novel imaging agents, targeted therapies, and approaches to managing malignant or recurrent disease. Individuals interested in participating in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility and available studies.