Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Abstract

Secondary hyperparathyroidism is one of the most common and serious complications of chronic kidney disease (CKD). The main factors responsible for excessive synthesis and secretion of parathyroid hormone (PTH) include phosphate retention, hypocalcaemia and calcitriol deficiency resulting from decreased kidney function [1,2]. Sustained hypersecretion of PTH is associated with an increase in the parathyroid gland size, initially leading to diffuse parathyroid hyperplasia. Subsequently, some cells in the parathyroid glands proliferate in a monoclonal growth pattern, and the enlarged glands exhibit an advanced type of nodular hyperplasia [3]. In the course of parathyroid hyperplasia, both calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) are progressively down-regulated [4,5], which results in diminished responsiveness of parathyroid glands with nodular hyperplasia to active vitamin D treatment.Conversely, whether regression of parathyroid hyperplasia can occur has remained a matter of discussion. Regression of parathyroid hyperplasia has been reported in rare cases of spontaneous infarction of the glands [6,7]. In addition, enhanced apoptosis of parathyroid cells has been observed in diffuse hyperplasia after kidney transplantation, suggesting the possibility of regression in the long term [8].In the past, the capacity of calcitriol therapy to induce regression of parathyroid hyperplasia had been a matter of debate. In a study of oral calcitriol pulse therapy, given to chronic haemodialysis patients, we observed a significant decrease in the mean ± SD volume of parathyroid glands (from 0.87 ± 0.32 to 0.51 ± 0.23 cm 3 ) after 12 weeks of treatment, with a concomitant significant reduction in intact PTH levels [9]. In contrast, Quarles et al. failed to observe a decrease in the parathyroid gland size after 36 weeks of intermittent intravenous or oral calcitriol treatments [10]; the mean ± SD gland volume was 1.9 ± 0.6 and 2.1 ± Correspondence and offprint requests to:

Failed Switching off in the MIBI-Parathyroid Scintigraphy in a Dialyzed Patient with Secondary Hyperparathyroidism Responsive to Cinacalcet Therapy

“…In agreement with these findings, parathyroid size regression after cinacalcet treatment has been recently reported in [12]. The literature is not yet clear if the inhibitory effect of cinacalcet on PTH secretion is associated with an effective control of parathyroid cell metabolism turnover, specially in parathyroid >0.5 cm 3 [13]. In our knowledge no data has been reported about the relationship between metabolic changes and MIBI uptake in haemodialysis patients treated with calcimimetic therapy; MIBI is a lipophilic radiotracer that becomes concentrated in cells and in mitochondria through active transport and passive diffusion.…”

Effective use of cinacalcet for the treatment of secondary hyperparathyroidism in Austrian dialysis patients – Results of the Austrian cohort of the ECHO study

“…Uremic patients with sHPT have reduced vitamin D receptor (VDR), CaSR, Klotho and FGFR1 expression in hyperplastic parathyroid tissue, even more pronounced in nodular parts [26][27][28][29]. Th is complicates the control of PTH secretion due to diminished responsiveness of parathyroid tissue to medical treatment [30]. Besides an improved biochemical response, calcimimetics have also been shown experimentally to upregulate VDR and CaSR expression in parathyroid glands [31,32].…”

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

“…However, there is controversy as to whether cinacalcet is capable of controlling parathyroid hyperfunction in patients with marked parathyroid hyperplasia (25,26). In addition, although experimental studies suggest that regression of parathyroid hyperplasia could be induced by calcimimetics (27,28), this possibility has not been adequately explored in the clinical setting (26,29).…”