UCLA study finds endocrine disorder is most common cause of elevated calcium levels
Unusually high calcium levels in the blood can almost always be traced to primary hyperparathyroidism, an undertreated, underreported condition that affects mainly women and the elderly, according to a new study by UCLA researchers.
The condition, which results from overactive parathyroid glands and includes symptoms of bone loss, depression and fatigue that may go undetected for years, is most often seen in African American women over the age of 50, the researchers discovered.
The study, currently online in the Journal of Clinical Endocrinology and Metabolism, is one of the first to examine a large, racially and ethnically diverse population — in this case, one that was 65 percent non-white. Previous studies had focused on smaller, primarily Caucasian populations.
The four parathyroid glands, which are located in the neck, next to the thyroid, regulate the body's calcium levels. When one is dysfunctional, it can cause major imbalances — for example, by releasing calcium from the bones and into the bloodstream. Over time, calcium loss from bones often leads to osteoporosis and fractures, and excessive calcium levels in the blood can cause kidney stones and worsening kidney function.
The UCLA researchers determined that hyperparathyroidism is the leading cause of high blood-calcium levels and is responsible for nearly 90 percent of all cases.
"The findings suggest that hyperparathyroidism is the predominant cause of high calcium levels, so if patients find they have high calcium, they should also have their parathyroid hormone level checked," said the study's lead author, Dr. Michael W. Yeh, an associate professor of surgery and endocrinology at the David Geffen School of Medicine at UCLA.
Hyperparathyroidism, which affects approximately 1 percent of the population, can be detected by measuring parathyroid hormone levels to determine if they are elevated or abnormal.
For the study, researchers utilized a patient database from Kaiser Permanente Southern California that included information on 3.5 million individuals, a population roughly the size of Ohio. Using data from lab results, the research team identified 15,234 cases of chronic high-calcium levels. Of those cases, 13,327 patients (87 percent) were found to have hyperparathyroidism.
The incidence of hyperparathyroidism — reported as the number of cases per 100,000 people per year — was found to be highest among African Americans (92 women and 46 men), followed by Caucasians (81 women and 29 men), Asians (52 women, 28 men) and Hispanics (49 women and 17 men).
The research team also found that with advancing age, the incidence of hyperparathyroidism (per 100,000 people per year) increased and that more women were affected:
- Under age 50: 12 to 24 cases for both genders
- Ages 50–59: 80 women and 36 men
- Ages 70–79: 196 women and 95 men
"It was surprising to find the highest incidence in black women over age 50," Yeh said. "We had traditionally thought of the disorder as affecting mostly Caucasian women."
However, since black women tend to have stronger bones and fewer fractures, more study is needed to see how the disorder is manifested in this patient group. African American women's physiology may be different and more protective of calcium and bone, Yeh said.
Yeh also noted that further study of the disorder may result in new, more targeted treatment guidelines based on racial differences. African American women, for instance, may require less vitamin D than is commonly prescribed to protect bone health, he said.
In the study, the researchers also found that the prevalence of hyperparathyroidism has tripled in the last 10 years, increasing from 76 women to 233 (out of 100,000) and from 30 men to 85.
The researchers noted that the growing prevalence is likely due to increased calcium testing, annual lab tests to monitor patients with symptoms and the low rate of surgery to treat the disorder. Previous research has shown that only 28 percent of patients with hyperparathyroidism undergo surgery to remove the overactive parathyroid gland — the most reliable way to correct the disorder.
"Women can suffer for years with hyperparathyroidism and not know they have it, which is especially critical in midlife, when bone health is so important," Yeh said. "Appropriate management of the disorder is essential. Surgery should be considered in the majority of people with primary hyperparathyroidism."
The next step, Yeh said, is further study of this patient population to examine the long-term impact of the condition on bone health and the effectiveness of different management strategies on outcomes.
"We are aiming to better understand how hyperparathyroidism affects people of different racial backgrounds," he said.
The study was funded with support from the Earl Gales Family Foundation, the National Institute on Aging and the American Geriatrics Society.
Additional authors include Philip H.G. Ituarte, Ph.D., Stacie Nishimoto and Dr. Avital Harari of the section of endocrine surgery at the David Geffen School of Medicine at UCLA; Hui Cynthia Zhou, In-Lu Amy Liu and Annette L. Adams, Ph.D., of the department of research and evaluation at Kaiser Permanente Southern California; and Dr. Philip I. Haigh of the department of surgery at Kaiser Permanente Los Angeles Medical Center.