The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have jointly issued the first-ever clinical practice guidelines for the management of patients with rare adrenal tumors such as pheochromocytoma and paraganglioma (referred to together as PPGL).
The new evidence-based guidance was published online June 3 in the Journal of Clinical Endocrinology and Metabolism by an international task force led by Jacques W. M. Lenders, MD, PhD, of Radboud University Nijmegen Medical Center, the Netherlands.
The document includes recommendations (based on strong evidence) and suggestions (based on weaker evidence) for biochemical testing, imaging studies, perioperative medical management, surgery, genetic testing, and personalized management. It also provides reasons to suspect PPGL, along with a chart of medications that can precipitate adverse reactions in patients who have the tumors.
While usually nonmalignant, PPGL can cause significant cardiovascular morbidity and mortality and can enlarge and extend into adjacent organs and tissues. The prevalence of PPGL in patients with hypertension seen in general outpatient clinics is between 0.2% and 0.6%.
The audience for the guidelines "spans from primary-care providers to endocrinologists," one of 3 United States–based task-force members, William F. Young, Jr, MD, chair of the division of endocrinology, diabetes, metabolism, and nutrition and professor of medicine at the Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News.
Rare Tumor Can Go Undetected, Leading to Death
"PPGL are rare tumors, and that is part of the problem," Dr. Young elaborated.
"It is so rare that most clinicians, although they learned something about it in medical school, rarely see PPGL in their careers. When they do see a patient who may have PPGL, they are frequently puzzled on the best case detection steps, what medications interfere with case detection testing, best imaging tests, etc."
Currently, the most common presentation of PPGL is the incidental finding of an adrenal or retroperitoneal mass on abdominal imaging performed for other reasons, he explained. If a pheochromocytoma is located extra-adrenally, it is defined as a paraganglioma.
The second most frequent presentation is poorly controlled high blood pressure, which may be associated with episodes of excessive sweating, heart pounding, headaches, tremor, and pallor, also known as "hyperadrenergic spells."
In some patients, the only sign may be resistant hypertension (ie, uncontrolled despite 3 blood-pressure medications). In others, Dr. Young added, the first sign of PPGL is a hypertensive response to anesthesia.
"I have seen patients with PPGLs who go undiagnosed — despite symptoms that should have triggered case detection testing — for many years, some more than a decade. The delay can have tragic consequences with metastatic and incurable disease, which leads to premature death — something that could have been prevented," he told Medscape Medical News.
Recommendations and Suggestions
The new guidelines give the following advice:
Biochemical Testing. In patients suspected of having PPGL, task-force members "recommend" biochemical testing via measurement of plasma free metanephrines or urinary fractionated metanephrines. They also "suggest" the use of liquid chromatography with mass spectrometry or electrochemical-detection methods over other laboratory methods.
Among the groups of patients who should have periodic biochemical testing for PPGL are those who have a known germ-line mutation that predisposes to PPGL, such as multiple endocrine neoplasia type 2, Dr. Young said.
Imaging Studies. Computed tomography (CT) is recommended as first line, rather than MRI, because of CT's "excellent spatial resolution for thorax, abdomen, and pelvis." However, the panel does recommend MRI in certain situations, such as for patients with metastatic PPGL, for those allergic to CT contrast material, and in those for whom radiation should be limited, such as pregnant women. Other imaging studies are described for certain specific types of patient.
Perioperative Medical Management. Preoperative blockade of hormonally functional PPGL to prevent cardiovascular complications is advised, as is preoperative medical treatment for 7 to 14 days to allow normalization of blood pressure and heart rate and a high-sodium diet with fluid intake to prevent severe hypotension after tumor removal.
Monitoring of blood pressure, heart rate, and glucose levels immediately after surgery is also recommended, while postoperative measurement of plasma or urine metanephrine levels and lifelong annual biochemical testing are "suggested."
Surgery. The task force recommends minimally invasive (eg, laparoscopic) adrenalectomy for most adrenal pheochromocytomas, with open resection reserved for very large or invasive pheochromocytomas. Open resection is suggested for paragangliomas, although laparoscopic resection is an option for smaller tumors. Partial adrenalectomy is also a possibility for certain types of patients.
Genetic Testing. The task force recommends that "all patients with PPGLs should be engaged in shared decision-making for genetic testing," with the use of "a clinical feature-driven diagnostic algorithm to establish the priorities for specific genetic testing in PPGL patients with suspected germ-line mutations."
The group also recommends that such genetic testing be "delivered within the framework of healthcare" that includes pre- and posttest genetic counseling.
Personalized Management. In general, in light of the "distinct genotype-phenotype presentations of hereditary PPGLs," the task force recommends a "personalized approach to patient management" within all of the above-mentioned areas. The group also recommends that patients with PPGLs be "evaluated and treated by multidisciplinary teams at centers with appropriate expertise to ensure favorable outcome."
Once PPGL Is Confirmed, Refer to Endocrinologist
Dr. Young told Medscape Medical News, "All healthcare providers should know when and how to test for PPGL. However, once case detection testing is positive, referral to an endocrinologist should be considered to facilitate a focused evaluation."
Although all of the diagnostic tests included in the document are covered by health insurance, "that obviously varies based on the company and specific policy." The panel did take cost-effectiveness into account in making its recommendations, he told Medscape Medical News.
The guideline was funded by the Endocrine Society. Neither Dr. Young nor any of the other task force members declared any relevant financial relationships.
J Clin Endocrinol Metab. Published online June 3, 2014. Abstract
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Cite this: Endocrine Society First to Address Rare Adrenal-Tumor Care - Medscape - Jun 05, 2014.
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