CHICAGO – More than half of patients who discontinue thiazide diuretics due to hypercalcemia will remain hypercalcemic even after stopping the drugs, and will eventually be diagnosed with primary hyperparathyroidism, according to a retrospective review from the Mayo Clinic in Rochester, Minn.
Those patients probably have subclinical primary hyperparathyroidism (PHP) disease before starting thiazides, and it may have contributed to their hypertension. In the study, PHP was likely unmasked by thiazide treatment, which reduces calcium excretion. "In our clinical practice, it’s not uncommon for us to stop thiazides, and then find calcium levels don’t normalize. Now we have data to confirm our clinical impression," said senior investigator Dr. Robert Wermers, an endocrinologist in the departments of endocrinology, diabetes, metabolism and nutrition at Mayo.
Dr. Robert Wermers
The finding is something to keep in mind when prescribing thiazides. In almost all patients, they were prescribed for hypertension. Hypercalcemia was an incidental finding in the study; none of the patients were symptomatic. Older women were most at risk for PHP, and surgery was the usual treatment, he said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
In all, the team reviewed 220 patients diagnosed with thiazide-associated hypercalcemia between 1992 and 2010. They were a median of 68 years old; 190 (86%) were women.
Eighty-one (37%) of those patients were taken off the drug; hypercalcemia persisted in 49 (60%) patients, of whom 43 (88%) were subsequently diagnosed with PHP.
The findings suggest that "primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics," the investigators said.
Compared with the overall patient population of 220, those who were diagnosed with PHP had a slightly higher maximum serum calcium while on thiazides (mean 10.9 vs. 10.7 mg/dL) and had been on thiazides a shorter period of time when hypercalcemia was detected (median 2.9 vs. 3.9 years). More than 80% of the patients in both groups were women, and the mean age at onset of hypercalcemia was about 67 years. Serum calcium was normal in both groups before thiazide treatment (median 9.7 mg/dL for both groups).
Of the 139 (63%) patients who stayed on thiazides despite hypercalcemia, 71 (51%) remained hypercalcemic, seven (5%) were eventually diagnosed with PHP, and calcium normalized in 68 (48.9%).
The overall incidence of thiazide associated hypercalcemia was 17 cases per 100,000 person-years. The highest rate was 314.3/100,000 person-years in women 65-74 years old. The incidence started climbing in the mid-1990s and peaked in 1999 at 31.7 cases per 100,000 person-years, perhaps because the guidelines released at the time that called for increased osteoporosis screening. In 2010, the incidence was about 20 cases per 100,000 person-years.
The investigators have no disclosures, and had no outside funding for the project.