PPGL is distinct, with unique implications for disease management. It is critical to understand the dual goals of treatment for this disease: tumor control and symptom reduction.
PPGL tumors are distinguished by the production, storage, and secretion of catecholamines and metanephrines, a process specific to tumors of chromaffin origin.
PPGL can have a wide range of clinical manifestations, with many patients experiencing frequent, acute, and severe symptoms.
In metastatic cases, additional morbidity can result from tumors invading and damaging organs.
Because symptoms are vague and frequent, there is an average delay of 3 years between the onset of symptoms and final diagnosis.
Over half of PPGL tumors are discovered incidentally during imaging studies for unrelated disorders. Some PPGL go undiscovered until death, with studies suggesting over 50% of all PPGL found at autopsy were not clinically suspected.
Due to the rarity of PPGL tumors and the vague and paroxysmal nature of the signs and symptoms, patients are at risk for a mistaken diagnosis. These diagnoses may include endocrine, psychiatric, or cardiovascular causes.
Common PPGL misdiagnoses include:
For patients experiencing symptoms, initial biochemical testing for plasma-free or urinary fractionated catecholamines and their metabolites can help establish diagnosis.
Ninety-five percent of PHEO and 77% of PGL express the norepinephrine transporter (NET) for the uptake of norepinephrine into cells.
MIBG is structurally similar to norepinephrine and, like norepinephrine, MIBG is taken up by NET and sequestered into vesicles by vesicular monoamine transporter (VMAT). MIBG can be labeled with radioactive I-123 or I-131 for diagnostic purposes, which may help detect metastases that cannot be detected by CT or MRI. Additionally, MIBG scintigraphy can help determine whether a patient is a candidate for targeted radiotherapy with I-131 labeled MIBG. I-131 MIBG is ideal for both diagnosis and therapy, and has been used in the treatment of metastatic PPGL since 1983.
While some patients can survive with metastatic disease for many years with minimal disease progression, others have extremely poor prognosis requiring urgent and decisive treatment. For patients with metastatic PPGL, 5-year overall survival can be as low as 12%, increasing the need for rapid intervention to improve outcomes.
Based on the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®), for patients with unresectable or metastatic PPGL, treatment may include one or a combination of FDA-approved and off-label treatments, including36: