SAN FRANCISCO — New guidelines for managing patients with asymptomatic primary hyperparathyroidism eliminate urine calcium as an indication for surgery and call for monitoring serum calcium annually instead of every 6 months in patients who do not have surgery.
The guidelines, the product of a 2008 international workshop and consensus panel, recommend parathyroidectomy for patients aged under 50 years with primary hyperparathyroidism (PHPT)and symptoms of hypercalcemia. Surgery also is recommended in asymptomatic patients whose serum total calcium is 1 mg/dL above the upper limit of normal, or whose estimated glomerular filtration rate is less than 60 mL/min, or who have bone mineral density T scores of −2.5 or lower at the lumbar spine, hip, or distal third of the radius on dual x-ray absorptiometry (J. Clin. Endocrinol. Metab. 2009;94:335–9).
The guidelines note that medical surveillance of patients who undergo surgery for primary hyperparathyroidism is neither possible nor desirable, Dr. Dolores M. Shoback said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.
For patients who don't go to surgery, the only change in monitoring recommendations compared with the last version of the guidelines in 2002 is the switch from semiannual to annual monitoring of serum calcium levels, said Dr. Shoback, professor of medicine at the university.
Serum creatinine and bone mineral density should be measured at three sites—lumbar spine, hip, and distal third of the radius—yearly. Tests that were included in 1990 guidelines but are no longer recommended include 24-hour urinary calcium, creatinine clearance, and abdominal x-ray.
No medications are approved to treat primary hyperparathyroidism. Studies of alendronate therapy show that it does not reverse or control the biochemical abnormalities of hyperparathyroidism, but it does seem to stabilize or even enhance bone mineral density in these patients. “It's a reasonable alternative” in patients who have low bone mass and hyperparathyroidism and who refuse surgery, or for those who are not good candidates for surgery, Dr. Shoback said.
The calcium mimetic cinacalcet also has been studied, with some promising results. Physicians might consider using this drug in patients with primary hyperparathyroidism to control hypercalcemia if the patients are too sick for surgery or declined or failed surgery, she said. The drug is approved in the European Union for this indication, she noted.
Dr. Shoback has been a consultant for Amgen, which markets cinacalcet, and was a researcher on a study examining the use of cinacalcet in parathyroid carcinoma patients.
Cinacalcet also might be useful to help clinicians decide whether surgery is necessary in patients with unclear symptomatology, such as depression, that could be an endogenous process related to aging or could be a result of hyperparathyroidism, she suggested. However, there are no data to support this idea, nor are there data to suggest that cinacalcet helps bone mineral density. And it's a very expensive drug, Dr. Shoback added.
The natural history of the disease was highlighted in what might be the largest and longest follow-up study that will be seen for a very long time, she said.
Among 116 patients with primary hyperparathyroidism (17 of whom were symptomatic), 51% went straight to surgery, which normalized biochemistries and improved bone mineral density in all patients during 15 years of follow-up (J. Clin. Endocrinol. Metab. 2008;93:3462–70; http://jcem.endojournals.org/cgi/content/short/93/9/3462).
Of the 57 patients who did not have surgery initially for a variety of reasons (although it was recommended to some), 8 were symptomatic, 5 were lost to follow-up, and 11 died over the 15-year period. Twenty patients went on to surgery; six of them because of disease progression.
Biochemically, patients who were followed tended to remain stable for the first decade but then developed significant increases in serum calcium levels. Bone density was stable in the lumbar spine but declined significantly after year 9 or 10 in the femoral neck and radius—by 10% and 35%, respectively. In comparison, bone density at these sites increased by 10% or more in patients who initially went to surgery.
Of eight patients who had kidney stones at baseline yet refused recommended surgery, six had recurrent stones during follow-up. Patients with kidney stones who agreed to initial parathyroidectomy had no recurrent stones.
“A history of kidney stones probably remains the tried-and-true good marker for somebody who should have this biochemical problem corrected,” Dr. Shoback said.
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