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

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Abstract

The aims of your case report is to show the predictivity of ^99mTc-sestamibi (MIBI) scintigraphy and doppler ultrasound imaging on secondary hyperparathyroidism (SHPT) in a patient responsive to calcimimetic treatment. Moreover, it has been reported that calcimimetic has great potential in reducing the volume of the parathyroid gland. On the other hand, the MIBI scintigraphy is considered a crucial diagnostic procedure to monitor the response to therapy in terms of turnover and cellular metabolism; whereas, ultrasound to monitor the volume variation in response to treatment. It is described the case of a 73-year-old man on hemodialysis from 1995 for ESRD. Within 2 years the patient gradually developed SHPT with progressively increased iPTH up to 1,000 ρg/ml. The ultrasound, highlighted the presence of two parathyroid hyperplasia, confirmed by scintigraphy, showing focal increase uptake of sestamibi in the same anatomical areas. As a result of the patient's refusal to perform a parathyroidectomy, cinacalcet, was administered (65 mg overage daily dose). After a year of treatment, there was a striking decrease of iPTH (from 1300 to 57 ρg/ml, −95%); but, on the contrary to expectations, this positive metabolic outcome, was not followed by parathyroid changes in ultrasound and scintigraphic findings.

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Most cited references 38

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Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

Geoffrey A Block, Kevin J Martin, Angel de Francisco … (2004)

Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism. Copyright 2004 Massachusetts Medical Society

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Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Douglas Brown, M Zhong, Andrew J. Finch … (1996)

Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH)2D3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)2D3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 +/- 25 vs. 35 +/- 3.5 pg/ml, P < 0.01), PTG weight (1.80 +/- 0.13 vs. 0.88 +/- 0.06 microg/gram of body weight, P < 0.01), and PTG DNA (1.63 +/- 0.24 vs. 0.94 +/- 0.07 microg DNA/gland, P < 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH)2D3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 +/- 215 vs. 1,033 +/- 209 pg/microg DNA, P < 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 microg/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3.

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Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients.

Eiji Uchida, , Shigeru Yumita … (2007)

Cinacalcet hydrochloride (KRN1493) acts on the parathyroid calcium receptors to suppress parathyroid hormone (PTH) secretion, and is already in wide use in the United States and the European countries. In this study, we examined the efficacy and safety of cinacalcet in Japanese patients on maintenance haemodialysis. One hundred forty-four patients with serum intact PTH (iPTH) levels >or=300 pg/ml were enrolled and randomly allocated to two groups assigned to receive either cinacalcet or placebo for 14 weeks. Cinacalcet was started at the dose of 25 mg/day and titrated up to 100 mg/day to achieve the target iPTH level of <250 pg/ml. Cinacalcet significantly decreased the median iPTH level from 606.5 pg/ml to 241.0 pg/ml, despite the mean dialysis vintage being 2.4 times longer (14.3+/-7.1 years) and the proportion of patients receiving vitamin D sterols being higher, than in the phase 3 studies conducted in the US/EU. The target iPTH level was achieved in 51.4% of the patients in the cinacalcet group, in sharp contrast to only 2.8% in the placebo group. Furthermore, the percentage of patients with both the serum calcium and phosphorus levels within the target range in the K/DOQI guidelines increased from 4.2% to 26.4% by cinacalcet. These results suggest that lower dose levels of cinacalcet, as compared to those in US/EU studies, may be sufficient effectively suppress the serum iPTH levels and allow favourable management of the serum calcium and phosphorus levels in Japanese patients, having a longer average dialysis vintage.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Endocrinol

Journal ID (publisher-id): IJE

Title: International Journal of Endocrinology

Publisher: Hindawi Publishing Corporation

ISSN (Print): 1687-8337

ISSN (Electronic): 1687-8345

Publication date (Print): 2010

Publication date (Electronic): 27 June 2010

Volume: 2010

Electronic Location Identifier: 206801

Affiliations

¹Territorial Nephrology and Dialysis Department, ASL, 8 Cagliari, via Turati 4/C-Quartu Sant'Elena, Cagliari, Sardinia, Italy

²Nuclear Medicine Department, Azienda Ospedaliero-Universitaria di Cagliari, 09124 Cagliari, Italy

³Radiology Department, Azienda Ospedaliero-Universitaria di Cagliari, 09124 Cagliari, Italy

Author notes

*Piergiorgio Bolasco: pg.bolasco@ 123456tin.it

Academic Editor: Mario Maggi

Article

DOI: 10.1155/2010/206801

PMC ID: 2905699

PubMed ID: 20652073

SO-VID: 2c65cf11-3a5e-4c54-a5f7-b5bef189e197

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 10 March 2010

Date revision received : 22 April 2010

Date accepted : 1 June 2010

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

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Most cited references 38

Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients.

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