Hyperparathyroidism Misunderstood and Underdiagnosed

Even though existing laboratory tests that measure calcium levels could easily detect primary hyperparathyroidism (PHPT), many patients with the condition go undiagnosed and untreated, according to a recent study in Surgery.

Researchers from Cleveland Clinic found that the disorder is much more common than previously documented. Their findings suggest that an estimated 43% of hypercalcemic patients are likely to have PHPT.

“Physicians may not be aware of how common hyperparathyroidism is, or that it is the most common cause of elevated serum calcium values,” says study co-author Allan Siperstein, MD, Chairman of the Center for Endocrine Surgery at Cleveland Clinic. “There is also the misconception that hyperparathyroidism is, for the large part, an asymptomatic condition such that the diagnosis is less important to pursue or treat.”

Yet, these patients have increased risk of osteoporosis and fracture, as well as a greater likelihood of kidney stones and renal damage. Less commonly recognized symptoms include weakness, fatigue, joint and muscle aches, and metabolic confusion. “In many ways, hyperparathyroidism is similar to high blood pressure in that it may not cause acute symptoms but may place a toll on the body over time,” Siperstein explains.

To study the prevalence of undiagnosed, unrecognized PHPT, he and his colleagues analyzed data from a large, tertiary referral center’s electronic medical record containing 6.5 million patients. They selected a 2-year study sample of 7,260 patients—all of whom had a primary care physician in the hospital system and outpatient serum calcium values greater than 10.5 mg/dL (hypercalcemia).

Just 1.3% had a recorded diagnosis of PHPT. Of the remaining patients, parathyroid hormone (PTH) values were recorded in 32%. About 70% of patients who had PTH measured were considered to have PHPT, defined as having a PTH value greater than 30 pg/mL. More than two-thirds (67%) of hypercalcemic patients had never obtained PTH values—28% of whom were likely to have PHPT.

The condition is 3 times as common in women as in men and increases with advancing age, according to Siperstein. Given that the basic metabolic panel typically includes serum calcium, most patients will already have undergone the initial screening test for this condition. Siperstein says that when elevated calcium levels are detected, the next step is to obtain a PTH value. “Key to the diagnosis of this condition is the understanding that many patients will not have a parathyroid hormone value above the ‘reference range,’ but rather a PTH that is inappropriately elevated in relationship to the serum calcium,” he explains.

While their initial study looked at a broad group of patients, the researchers are now looking at higher-risk populations, such as those with osteoporosis or kidney stones, as this group may be best helped with earlier recognition and treatment of PHPT.

—Colleen Mullarkey


Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Jin J, et al. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: A population-based analysis from the electronic medical record. Surgery. 2013 Dec;154(6)1232-8.