When the COVID-19 crisis forced New York State hospitals to delay all nonurgent surgeries, clinicians at Mount Sinai’s Adrenal Center were able to medically manage three patients with newly-diagnosed pheochromocytomas for longer than the recommended preoperative preparation time period. The subsequent successful surgical outcomes for all three show that such an approach is feasible in patients with only mild symptoms and well-controlled blood pressure, according to Alice C. Levine, MD, Director of the Mount Sinai Adrenal Center.
Pheochromocytomas, or “pheos,” are neuroendocrine adrenal tumors that secrete catecholamines into the circulation. In large amounts, this can lead to “adrenergic crisis” with potential organ failure and death. Current guidelines aim to avert serious sequelae due to this “ticking time bomb” with 7 to 14 days of medical antihypertensive medications followed by surgical adrenalectomy. However, because these tumors are increasingly being picked up incidentally rather than due to symptoms, it is becoming apparent that not all pheos are endocrine emergencies, Dr. Levine says.
“It’s very different from what it used to be. In more recent days, pheos are often noted incidentally in asymptomatic patients,” says Dr. Levine, Professor of Medicine (Endocrinology, Diabetes and Bone Disease), Icahn School of Medicine at Mount Sinai. “The patient had an MRI or CT scan of the abdomen for another reason, and a small tumor was detected. Many of these are not secreting large amounts of excess catecholamines. In such cases, patients may have no hypertension or symptoms, or mild illness easily controlled with medications." Traditionally, a diagnosis of pheochromocytoma was considered an endocrine emergency. But in patients with less secretory tumors, discovered incidentally, medical management can be prolonged and surgery delayed.
“It’s a more heterogeneous group than in the past. And for many of those picked up incidentally, as long as they’re on some medication, they’re not in great danger.”
- Alice C. Levine, MD
Alice C. Levine, MD, left, with Endocrine Fellow Eva Alba, MD.
In a paper published in the Journal of the Endocrine Society, Dr. Levine reported on the three patients first seen in March 2020. Co-authors of the paper are all current or former Endocrinology fellows at Icahn Mount Sinai: Amanda Leiter, MD, Clinical Instructor of Medicine (Endocrinology, Diabetes and Bone Disease), Icahn Mount Sinai; Effie A. Tsomos, MD, an endocrinologist at Mount Sinai South Nassau; Sarah A. Reda, MD, Endocrine Fellow at The Mount Sinai Hospital; and Emily Japp, MD, Assistant Professor of Medicine (Endocrinology) at the University of Maryland Medical Center.
All of the patients were women, ages 60 (case 1), 67 (case 2), and 84 (case 3). In all three, the pheo had been detected incidentally, and all had hypertension that was well-controlled on antihypertensive monotherapy. Case 1 was asymptomatic, while the other two had mild tremors, sweating, and palpitations. Due to pandemic “Pause” rules on semi-elective surgeries, their adrenalectomies were postponed by 7, 13, and 18 weeks, respectively.
Preoperative medication for case 1 involved merely upping her amlodipine dose by 2.5 mg. Case 2 received terazosin and metoprolol in place of lisinopril, while case 3 had amlodipine added to the ramipril she was already taking. All monitored their blood pressure and symptoms at home and kept in close touch with the Adrenal Center staff via telemedicine.
Cases 1 and 3 did not receive the traditional alpha-adrenergic blockade, a personalized approach that Dr. Levine says was appropriate for these patients.
“We didn’t know how long they would be on these drugs prior to the surgery. Some of the alpha-adrenergic blockers are expensive and hard to obtain, and also poorly tolerated due to side effects such as orthostatic hypotension and tachycardia,” Dr. Levine says. “We were managing them by telehealth, so we had to be a little more conservative. There is strong evidence that in milder cases, calcium channel blockers work well to control blood pressure and symptoms.”
The Mount Sinai Adrenal Center has been pulling back on the “iron-clad rule of alpha-adrenergic blockers” for several years, Dr. Levine says, as the team wrote into a clinical pathway in 2015. That publication has been widely read and highly cited.
Certainly, larger pheos in symptomatic patients with labile hypertension are high-risk, and urgent adrenalectomy after two weeks of alpha-blockade remains the treatment of choice. But Dr. Levine notes that for those at lower risk, more prolonged medical management prior to surgery may be advantageous as it allows time for the patient to undergo adrenalectomy at a highly specialized “quaternary” center such as Mount Sinai. There, the Adrenal Center team includes surgeons, anesthesiologists, endocrinologists, and other experts in the pre-, peri-, and post-operative management of pheochromocytomas.
“This is a relatively rare disorder, and many community hospitals lack experience in the management of pheos, which can be tricky," Dr. Levine says. "If a patient lives far away from a hospital with an expert team and is asymptomatic on medications, it makes sense to hit the pause button on surgical adrenalectomy until they can be operated on at a pheochromocytoma center of excellence to insure a safe landing for patients with this rare endocrine tumor."