Benign Tumors That Cause Big Problems
By Bryan Tutt
About 100,000 people in the United States, most of them women, are diagnosed with primary hyperparathyroidism each year. About 90% of these cases are caused by a single benign tumor, or adenoma, in one of the parathyroid glands, while a small number involve multiple glands. About 5% of parathyroid tumors are caused by familial syndromes.
In some of these syndromes, notably multiple endocrine neoplasia type 1, benign tumors of the parathyroid are the first manifestation of disease, followed by potentially malignant tumors in other parts of the body, such as the pancreas. Identifying this form of parathyroid disease can help doctors screen, monitor, and provide earlier intervention for the prevention or treatment of malignant disease.
The symptoms of hyperparathyroidism result from the excess production of parathyroid hormone (PTH). High levels of PTH in the body signal for calcium increases in the blood. Because much calcium is stored in the bones, high PTH levels can lead to osteopenia or osteoporosis. According to Nancy Perrier, M.D., a professor in The University of Texas MD Anderson Cancer Center’s Department of Surgical Oncology, Section of Surgical Endocrinology, patients with hyperparathyroidism are often diagnosed because of these skeletal manifestations, which cause cortical bone reduction. “If on routine screening a primary care physician identifies osteoporosis, consideration should be given to a high level of PTH workup and discussion to understand whether the patient has hyperparathyroidism,” she said, adding that some patients with parathyroid tumors present with nonspecific symptoms like fatigue, depression, aches and pains, or even kidney stones.
An elevated or high normal blood calcium level can be an indicator of hyperparathyroidism. Because high blood calcium can have other causes—such as metastatic tumors, myeloma, breast cancer, or some medicines—the patient’s serum PTH level should be tested to make the diagnosis of hyperparathyroidism. In healthy patients, when serum calcium is high, the PTH level should be low, and vice versa. People with hyperparathyroidism have high levels of both calcium and PTH.
While some asymptomatic patients have the option of medical observation, patients with symptoms need to undergo a parathyroidectomy. “If they have osteoporosis, kidney stones, broken bones, or a hypercalcemic crisis, then they need an operation to remove the parathyroid adenoma,” Dr. Perrier said.
Minimally invasive procedure
Fortunately, most parathyroid tumors can be removed by minimally invasive parathyroidectomy in an outpatient setting. Dr. Perrier said that about 200 of these procedures are done each year at MD Anderson.
Although the surgery is in a high-risk region, parathyroidectomy is a fairly quick procedure for experienced surgeons. With the patient sedated, the neck is hyperextended, and the surgeon makes an incision about 2 cm long. “The precise incision location is based on preoperative imaging studies. The goal is to minimize the dissection, allowing for a very focused procedure,” Dr. Perrier said. Once the surgeon has removed the gland with the suspected tumor, an immunochemiluminescent assay is used to determine whether the patient’s serum PTH level has decreased. Because the half-life of PTH is 3 minutes, a decreased PTH level at 5 minutes, confirmed by a second test at 10 minutes, verifies that the surgeon has removed the gland that is causing the problem. “We close the incision, the patient goes to the recovery room, and then the patient goes home 4–6 hours later,” Dr. Perrier said. Because only 3% of patients experience a recurrence of parathyroid tumors, doctors at MD Anderson typically see patients for immediate and 6-month follow-up visits and send them back to their referring physicians.
Roadmap for surgery
Imaging studies are crucial to the success of minimally invasive parathyroidectomies. Dr. Perrier described these imaging studies as a roadmap for surgery. “If we know exactly where the adenoma is, we can target our incision and minimize the dissection,” she said. Although a parathyroidectomy could be done without preoperative imaging, the surgeon would have to make a larger incision and then explore the cervical region to locate the tumor-containing gland. “With the imaging, we know where the gland is before we make the incision,” Dr. Perrier said. Although some institutions use a radio-guided probe to locate the adenoma, Dr. Perrier said that the imaging studies done before the operation make the probe unnecessary.
Beth S. Edeiken-Monroe, M.D., a professor in MD Anderson’s Department of Diagnostic Radiology, said at least two imaging studies—usually ultrasonography plus four-dimensional computed tomography, a nuclear medicine study, or both—are done on most patients before surgery. The combination depends mainly on the patient’s body habitus and whether or not the patient has had prior surgery. Dr. Edeiken-Monroe does the ultrasonography studies for many of Dr. Perrier’s patients and said the test is done to locate the parathyroid tumor and also to check for tumors of the thyroid gland. She finds concomitant malignant thyroid tumors in 6%–8% of the patients she sees who have parathyroid disease. In these cases, the surgeon would remove both the thyroid and parathyroid glands that had tumors at the time of the surgical procedure.
To facilitate communication between radiologists, surgeons, and other specialists, a classification system was developed at MD Anderson in which the possible locations of the parathyroid glands are labeled alphabetically, A–G. “The radiologist can read the report and say that the tumor is in a left-side, type B gland, and we’ll know exactly what that means in relation to important structures like the thyroid, the recurrent laryngeal nerve, and the carotid,” Dr. Perrier said.
Benefits of treatment
Research shows up to 15% improvement in bone density 2–5 years after parathyroidectomy. “That’s very significant for individuals, particularly postmenopausal women or women with bone loss,” Dr. Perrier said. “No drug will increase bone density like curing this disease will.”
Improved bone density is not the only benefit of parathyroid surgery. The high calcium and PTH levels, which are alleviated by the surgery, could put untreated patients at a higher risk for cardiovascular disease and carotid artery distensibility. High levels can also affect cognitive function. “We completed a randomized controlled trial here at MD Anderson that demonstrated that patients had improved functional performance and sleep following parathyroidectomy,” Dr. Perrier said. These results suggest that high PTH levels affect circadian rhythms and disrupt stage 4 sleep in patients, impairing verbal memory, learning, and attention. “This can be very critical in elderly patients who already are declining in these areas. If we can restore their independence by curing a metabolic problem, we might prevent downstream disability.” Dr. Perrier and her colleagues also observed that, in the patients who underwent surgery, decreased PTH levels correlated with the ability to walk farther. “Parathyroidectomy really does improve functional capacity,” she said, “even in patients with a parathyroid adenomas who appear to be asymptomatic.”
The future of surgery
Although a minimally invasive parathyroidectomy leaves a scar of only 1–2 cm on the neck, Dr. Perrier is excited about a new robotic procedure in which the incision is virtually invisible. Surgeons at MD Anderson were the first in the United States to perform a parathyroidectomy using the robot. “We make an incision under the arm,” Dr. Perrier said. “Then we deploy small instruments that have excellent precision when guided from a console. Additionally, a high-definition videoscope offers improved visualization of the anatomy. We use our feet to manipulate the scope, and we use our hands to manipulate the instruments.” Dr. Perrier said she and other surgeons have done about a dozen thyroid resections and a few parathyroidectomies with the robot thus far.
Perrier ND, Balachandran D, Wefel JS, et al. Prospective, randomized, controlled trial of parathyroidectomy versus observation in patients with “asymptomatic” primary hyperparathyroidism. Surgery 2009; 146:1116–1122.Perrier ND, Edeiken B, Nunez R, et al. A novel nomenclature to classify parathyroid adenomas. World J Surg 2009; 33:412–416.
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