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Medical treatment for primary hyperparathyroidism impairs endothelial function
Adults with primary hyperparathyroidism treated medically have decreased flow-mediated dilation compared with adults treated for primary hyperparathyroidism with surgery and those with normal calcium levels, study data show.
Researchers also found that vitamin D supplementation may improve flow-mediated dilation in adults being medically treated with low 25-hydroxyvitamin D levels.
Sevgi Colak, MD, of the department of internal medicine at the University of Ankara, Ibni Sina Hospital in Turkey, and colleagues evaluated 29 adults with primary hyperparathyroidism receiving medical treatment, 25 preoperative adults with primary hyperparathyroidism, 23 postoperative adults with primary hyperparathyroidism and 26 normocalcemic adults. Researchers sought to investigate endothelial dysfunction and markers of subclinical atherosclerosis in primary hyperparathyroidism and to demonstrate the effect of vitamin D supplementation on the parameters. Overall, 80.6% of participants were women, and the mean age was 56.3 years.
Participants were evaluated by measurements of flow-mediated dilation, carotid intima-media thickness, and serum levels of soluble CD40 ligand, high-sensitivity C-reactive protein and interleukin-8.
The preoperative primary hyperparathyroidism group had higher incidences of osteoporosis (P = .003) and nephrolithiasis (P = .001) compared with the other groups.
The medical treatment group had lower serum corrected calcium levels compared with the preoperative group (P < .001) and higher levels compared with the postoperative and normocalcemic groups (P < .001), according to the researchers. The corrected calcium levels were highest in the preoperative group (P < .001). The medical treatment and preoperative groups had higher parathyroid hormone levels compared with the postoperative and normocalcemic groups (P < .001). The preoperative group had lower serum phosphorus levels compared with the medical treatment group (P = .005) and the postoperative and normocalcemic groups (P < .001 for both).
The medical treatment group had lower flow-mediated dilation (5%) compared with the postoperative group (7.6%; P = .02) and normocalcemic group (7.7%; P = .02), but similar flow-mediated dilation to the preoperative group (5.1%).
After exclusion of participants with diabetes, the median flow-mediated dilation was lower in the medical treatment group compared with the postoperative and normocalcemic groups (P < .01), the researchers wrote.
In the medical treatment group, a subgroup of 13 participants with low levels of 25-(OH)D were assessed before and 3 months after vitamin D replacement. After replacement, serum 25-(OH)D levels increased to a mean 70.4 nmol/L from 33.9 nmol/L (P = .006) and median flow-mediated dilation increased to 7.07% from 4.71% (P = .02).
“Clinicians must consider cardiovascular risks in addition to guideline advice when making treatment decisions in [primary hyperparathyroidism] patients,” the researchers wrote. “In our opinion, vitamin D replacement in [primary hyperparathyroidism] patients with low vitamin D levels is an important treatment for not only reducing the disease severity, but also for providing CV gains. How accurately the [flow-mediated dilation] measurements in [primary hyperparathyroidism] patients can identify CV risk, whether this risk can be decreased with parathyroidectomy, and whether [flow-mediated dilation] measurements should routinely be used in treatment decisions in [primary hyperparathyroidism] patients will need to be clarified with further research. Vitamin D supplementation also seems to be a suitable option to improving possible CV risks in medically observed patients with [primary hyperparathyroidism], at least for those who are vitamin D deficient.” – by Amber Cox
Disclosures: The researchers report no relevant financial disclosures.
Perspective
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Colak and colleagues conducted a comparative cohort study to evaluate the impact of primary hyperparathyroidism on markers of subclinical atherosclerosis and CVD risk. Interestingly, flow-mediated dilation was significantly lower in patients with hyperparathyroidism being treated medically compared with operatively treated patients and normal controls. The researchers also observed an improvement in flow-mediated dilation when low vitamin D levels were replenished in deficient hyperparathyroid patients.
Some of the many possible manifestations of hyperparathyroidism are relatively easy to trace back to calcium metabolism, such as nephrolithiasis and osteoporosis. The mechanistic relationship between CVD and hyperparathyroidism is less obvious. The researchers’ findings are important not only because of the demonstrable difference in flow-mediated dilation, but also because postoperative patients had values quite similar to the normal controls. Their findings contribute to the growing body of literature suggesting that surgery can reverse the endothelial dysfunction associated with hyperparathyroidism, even in otherwise asymptomatic patients. Supplementing vitamin D in deficient patients might be a good option to mitigate endothelial dysfunction when patients are not operative candidates. Also, the impact of vitamin D replacement might provide a clue to the mechanism behind which hyperparathyroidism affects CV risk. For patients who are surgical candidates, vitamin D can be rapidly and safely replaced postoperatively thereby avoiding the potential risk for exacerbating hypercalcemia.