Decreases in Parathyroid Gland Volume after Cinacalcet Treatment in Hemodialysis Patients with Secondary Hyperparathyroidism

Abstract

Background/Aim: Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment. Methods: Ultrasonography of the parathyroid glands was performed to examine the changes in the parathyroid gland volumes after cinacalcet treatment in 58 patients. Results: After cinacalcet treatment, serum calcium, phosphate, alkaline phosphatase, and intact PTH significantly decreased (p < 0.0001). The total volumes of the parathyroid glands were significantly decreased 6 months after cinacalcet treatment (942 ± 747 vs. 708 ± 550 mm³, p < 0.0005). There was a significant positive correlation between the parathyroid gland volumes at the start of cinacalcet treatment and the volume reduction in parathyroid glands (r = 0.716, p < 0.0001). Of the 58 patients, the total parathyroid gland volume was decreased in 42 patients and increased in 16 although the doses of cinacalcet, phosphate binders or vitamin D were not significantly different. In both groups, the intact PTH serum levels were significantly decreased after cinacalcet treatment. Conclusion: Cinacalcet treatment in patients with secondary hyperparathyroidism significantly reduced the total parathyroid gland volume in a short 6-month period. This study suggests that cinacalcet treatment may postpone parathyroidectomy and/or reduce cases.

Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy

“…Nevertheless, this study does not allow to determine whether a regression of PTG with DH is possible after cinacalcet therapy. Actually, this hypothesis has been first based on the data obtained in experimental studies (18,19,20,21,22,23) and then by the US evaluation of PTG (28,29,30,31,32).…”

“…With regard to US, some authors reported that the PTG volume reduced significantly (28,29,30), areas of cystic degeneration appeared, and glandular vascularization decreased (29) after cinacalcet therapy with consequent reduced functioning PTG mass. Indeed, in agreement with Sumida et al, we found that the number of PTG with macroscopic hemorrhagic or cystic areas was similar in the two groups of HP and that only the weight of PTG predicted the presence of hemorrhagic areas.…”

“…Some authors (28,29,30) reported a significant reduction in the PTG volume from baseline to the end of the follow-up.…”

Cinacalcet Induces Apoptosis in Parathyroid Cells in Patients with Secondary Hyperparathyroidism: Histological and Cytological Analyses

“…Previous studies have shown that treatment with cinacalcet effectively reduces PTH secretion and gland volume in patients with SHPT [7,8,9]; however, it has been unclear whether cinacalcet accelerates apoptosis of hyperplastic parathyroid cells. In this study, we have shown that the proportion of parathyroid cells undergoing apoptosis, as assessed by the TUNEL assay, a common method for detecting DNA fragmentation, was significantly increased in patients treated with cinacalcet compared to those without.…”

“…A large number of trials have shown that cinacalcet simultaneously reduces PTH, calcium and phosphate in patients with SHPT [2,3,4,5,6]. Recent studies also demonstrated a significant reduction in parathyroid gland volume during treatment with cinacalcet [7,8,9], suggesting that cinacalcet may induce regression of parathyroid hyperplasia in dialysis patients with SHPT.…”