Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism

Abstract

Background. The effect of cinacalcet on the structural pattern of hyperplastic parathyroid glands was evaluated, using high-resolution colour Doppler (CD) sonography, in haemodialysis patients with severe, inadequately controlled, secondary hyperparathyroidism (sHPT).Methods. Nine patients (6 males, 3 females; mean age ± SD, 55.5 ± 12.6 years) received cinacalcet, with adaptation of existing concomitant therapies. Biochemical parameters and the morphology and vascular pattern of hyperplastic parathyroid glands were measured at baseline and every 6 months thereafter, for a follow-up period of 24–30 months.Results. At baseline, 28 hyperplastic glands were identified. Cinacalcet led to a reduction in glandular volume during the course of the study: 68% in glands with a baseline volume <500 mm3 and 54% in glands with a baseline volume ≥500 mm3. The mean volume ± SD of glands <500 mm3 changed significantly from the baseline (233 ± 115 mm3) to the end of follow-up (102 ± 132 mm3, P = 0.007). Levels of mean serum phosphorus, calcium and calcium–phosphorus product decreased, but not significantly, whereas there were significant decreases in mean parathyroid hormone ± SD levels (1196 ± 381 pg/ml versus 256 ± 160 pg/ml; P < 0.0001) and alkaline phosphatase ± SD levels (428 ± 294 versus 223 ± 88 IU/l; P = 0.04), accompanied by an improvement in a subjective clinical score.Conclusions. Cinacalcet, in combination with conventional treatments, led to an improvement in biochemical and clinical parameters of sHPT and reduced glandular volume in patients with severe sHPT. Volume reduction was more evident in smaller glands. Longer term, larger, randomized clinical trials are needed to confirm these preliminary findings and to further define a more systematic approach in the treatment of sHPT.

Surgical management of secondary hyperparathyroidism in chronic kidney disease—a consensus report of the European Society of Endocrine Surgeons

“…After PTX, there is a constant decline in renal function, probably due to haemodynamic effects of PTH on the preglomerular and efferent arterioles [49]. It should be noted, however, that current studies suggest that the graft survival is not decreased by PTX [47,132,135,140]. It seems that the risk and intensity of the decrease of renal function are highly dependent on the severity of HPT (high level of PTH) and probably on the slope of decline, and therefore avoiding/reducing post-PTX hypoparathyroidism and hypocalcaemia could reduce the risk of significant decline of the renal function [129] It is therefore expected that a less aggressive parathyroid resection should lead to a less important decline in PTH and therefore to a decreased risk of decline of renal function.…”

“…Its introduction decreases renal function, which is reversible after cessation, suggesting the same haemodynamic effect like PTX. Some studies observed a regression of parathyroid gland volume on ultrasonography with cinacalcet [132,133] (EL 3), but its effect on urinary calcium excretion is not known and studies reported contradictory results (unchanged, increased or reduced calcium excretion) [107]. Above all, cinacalcet is only approved for treatment of renal HPT and is very expensive [134] (EL 2), rendering PTX as primary effective and longterm option for transplanted patients.…”

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

“…More recent studies suggest that combined therapy with cinacalcet and low doses of vitamin D sterols could be an effective strategy to treat SHPT while adequately maintaining acceptable levels of calcium and phosphorus (22)(23)(24). 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).…”

“…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).…”

Review of cinacalcet hydrochloride in the management of secondary hyperparathyroidism

“…18,19 Long-term combination of cinacalcet with standard therapy has been shown to reduce parathyroid hyperplasia. 20 …”