Research News

While many tumors of the adrenal gland are benign (noncancerous), they can cause life-threatening disease due to an overproduction of “fight-or-flight” hormones. One such tumor type is called pheochromocytoma.

The normal human body has two adrenal glands that serve important functions. The outer portion of the gland is called the cortex and produces hormones essential to life, such as cortisol, which provides the body with energy and maintains blood pressure. The inner portion of the adrenal gland is called the medulla, which produces adrenaline, or the fight-or-flight hormones. 

Pheochromocytomas affect the medulla and cause an overproduction of adrenaline, which can lead to hypertension, profuse sweating, headaches, panic attacks, arrhythmia, stroke and even death. The disease can arise spontaneously, but is often associated with mutations in certain genes. Patients with disease-causing mutations are at higher risk for developing subsequent tumors

The current standard treatment for pheochromocytoma affecting both adrenals, is removal of both adrenal glands (total adrenalectomy). While this treatment eliminates the potential of developing new tumors, patients require life-long hormone replacement therapy to compensate for the loss of their adrenal function.

Recent data suggest that preserving as much of the adrenal cortex as possible (cortical-sparing adrenalectomy) can reduce the need for hormone replacement therapy, which in itself presents unique health risks. However, research evidence for clinically recommending this procedure is weak, as the risk of tumor recurrence and metastasis is higher and long-term efficacy is not well understood.

To address this knowledge gap, an international team of researchers co-led by Charis Eng, MD, PhD, Genomic Medicine Institute, Cleveland Clinic, analyzed long-term outcomes in 625 patients with bilateral pheochromocytomas who underwent total or cortical-sparing adrenalectomy. Published in JAMA Network Open, the results show that hormone therapy after bilateral total adrenalectomy resulted in adrenal crisis (a state caused by insufficient cortisol levels) or Cushing syndrome (a condition caused by an excess of prescribed cortisol that can be fatal if left untreated). Conversely, the cortical-sparing procedure was not associated with worse outcomes or higher morbidity, even when tumors recurred.

Furthermore, cortical-sparing adrenalectomy is often ideal for individuals with hereditary pheochromocytoma as they are at higher risk for developing new tumors that would require additional surgeries. Genetic analyses of the study participants revealed a high percentage (96%) of patients had germline mutations associated with bilateral pheochromocytoma; however, clinical features of predisposing mutations are not always evident.  For example, many patients who eventually develop bilateral pheochromocytoma often present for the first time with only one pheochromocytoma affecting one adrenal gland. When this occurs, surgeons often perform total adrenalectomy. This is problematic when the second pheochromocytoma occurs in the opposite gland, leaving few options. Therefore, the research team recommends that all patients presenting with pheochromocytomas should be offered genetic analysis to guide surgical and medical management decisions.

In summary, the multidisciplinary group of researchers concluded that cortical-sparing surgery can be appropriate and safe for certain cases of bilateral pheochromocytoma, particularly when a predisposing mutation is present. Since clinical features of predisposing mutations are not always evident, this study underscores the importance of genetic testing in diagnosing and managing pheochromocytoma.

Dr. Eng is the inaugural chair of Cleveland Clinic Lerner Research Institute's Genomic Medicine Institute and inaugural director of the Center for Personalized Genetic Healthcare, which includes a subspecialty clinic available to children and adults with a confirmed or possible diagnosis of a hereditary susceptibility to pheochromocytoma. She also holds the Sondra J. and Stephen R. Hardis Endowed Chair in Cancer Genomic Medicine, is a member of the National Academy of Medicine, and in 2018, received the Medal of Honor from the American Cancer Society.