Skip to main content
SpringerLink
Log in

Reduction in parathyroid adenomas by cinacalcet therapy in patients with primary hyperparathyroidism

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Cinacalcet is a calcimimetic that modulates the functions of calcium-sensing receptor and is currently used to treat patients with primary hyperparathyroidism (PHPT). Although it was reported that cinacalcet treatment reduced the size of hyperplastic parathyroid glands in patients with secondary hyperparathyroidism, whether or not cinacalcet treatment can reduce the size of parathyroid adenomas in patients with PHPT has been unknown.

Materials and methods

We recruited nine (male: one, female: eight) patients with PHPT due to parathyroid adenomas who did not undergo parathyroidectomy. Cinacalcet was administered at a dose of 50 mg/day, and we evaluated the size of parathyroid adenomas (width × thickness) (mm2) using ultrasonography before and after 6 months of cinacalcet treatment.

Results

The mean age of the subjects was 58.1 ± 7.2 years old, and the mean serum intact parathyroid hormone (PTH) concentration was 134.8 ± 8.7 pg/ml. All participants showed hypercalcemia and osteopenia. After 6 months, the mean size of parathyroid adenomas was significantly decreased (baseline: 73.8 ± 33.4 mm2 vs. after 6 months: 52.5 ± 25.0 mm2, p = 0.045). Thus, 6-month cinacalcet treatment induced a 29% size reduction in parathyroid adenomas. Furthermore, the serum intact PTH concentration before cinacalcet treatment was positively correlated with the reduction in the size of parathyroid adenomas.

Conclusion

The present study revealed that cinacalcet treatment reduces the size of parathyroid adenomas in patients with PHPT. The accumulation of more PHPT cases with cinacalcet therapy is required to confirm this finding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Adami S, Marcocci C, Gatti D (2002) Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res 17(Suppl 2):N18-23

    PubMed  Google Scholar 

  2. Wermers RA, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS, Melton LJ 3rd (2006) Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993–2001: an update on the changing epidemiology of the disease. J Bone Miner Res 21:171–177

    Article  Google Scholar 

  3. Yu N, Donnan PT, Murphy MJ, Leese GP (2009) Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK. Clin Endocrinol (Oxf) 71:485–493

    Article  Google Scholar 

  4. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, Haigh PI, Adams AL (2013) Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 98:1122–1129

    Article  CAS  Google Scholar 

  5. Insogna KL (2018) Primary hyperparathyroidism. N Engl J Med 379:1050–1059

    Article  Google Scholar 

  6. Udelsman R (2002) Six hundred fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 235:665–670 (discussion 670-662)

    Article  Google Scholar 

  7. Chan AK, Duh QY, Katz MH, Siperstein AE, Clark OH (1995) Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. A case–control study. Ann Surg 222:402–412 (discussion 412-404)

    Article  CAS  Google Scholar 

  8. Talpos GB, Bone HG 3rd, Kleerekoper M, Phillips ER, Alam M, Honasoge M, Divine GW, Rao DS (2000) Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey. Surgery 128:1013–1020

    Article  CAS  Google Scholar 

  9. Vestergaard P, Mosekilde L (2003) Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism. BMJ 327:530–534

    Article  Google Scholar 

  10. Rao DS, Phillips ER, Divine GW, Talpos GB (2004) Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab 89:5415–5422

    Article  CAS  Google Scholar 

  11. Aace Aaes Task Force on Primary Hyperparathyroidism (2005) The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract 11:49–54

    Google Scholar 

  12. Kawata T, Imanishi Y, Kobayashi K, Onoda N, Okuno S, Takemoto Y, Komo T, Tahara H, Wada M, Nagano N, Ishimura E, Miki T, Ishikawa T, Inaba M, Nishizawa Y (2006) Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels. J Bone Miner Metab 24:300–306

    Article  CAS  Google Scholar 

  13. Peacock M, Bolognese MA, Borofsky M, Scumpia S, Sterling LR, Cheng S, Shoback D (2009) Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a five-year study. J Clin Endocrinol Metab 94:4860–4867

    Article  CAS  Google Scholar 

  14. Meola M, Petrucci I, Barsotti G (2009) Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism. Nephrol Dial Transplant 24:982–989

    Article  CAS  Google Scholar 

  15. Ichii M, Ishimura E, Okuno S, Chou H, Kato Y, Tsuboniwa N, Nagasue K, Maekawa K, Yamakawa T, Inaba M, Nishizawa Y (2010) Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism. Nephron Clin Pract 115:c195-202

    Article  CAS  Google Scholar 

  16. Komaba H, Nakanishi S, Fujimori A, Tanaka M, Shin J, Shibuya K, Nishioka M, Hasegawa H, Kurosawa T, Fukagawa M (2010) Cinacalcet effectively reduces parathyroid hormone secretion and gland volume regardless of pretreatment gland size in patients with secondary hyperparathyroidism. Clin J Am Soc Nephrol 5:2305–2314

    Article  CAS  Google Scholar 

  17. Nagano N (2006) Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism. Pharmacol Ther 109:339–365

    Article  CAS  Google Scholar 

  18. Sumida K, Nakamura M, Ubara Y, Marui Y, Tanaka K, Takaichi K, Tomikawa S, Inoshita N, Ohashi K (2011) Histopathological alterations of the parathyroid glands in haemodialysis patients with secondary hyperparathyroidism refractory to cinacalcet hydrochloride. J Clin Pathol 64:756–760

    Article  CAS  Google Scholar 

  19. Nemeth EF, Heaton WH, Miller M, Fox J, Balandrin MF, Van Wagenen BC, Colloton M, Karbon W, Scherrer J, Shatzen E, Rishton G, Scully S, Qi M, Harris R, Lacey D, Martin D (2004) Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J Pharmacol Exp Ther 308:627–635

    Article  CAS  Google Scholar 

  20. Colloton M, Shatzen E, Miller G, Stehman-Breen C, Wada M, Lacey D, Martin D (2005) Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int 67:467–476

    Article  CAS  Google Scholar 

  21. Imanishi Y, Kawata T, Kenko T, Wada M, Nagano N, Miki T, Arnold A, Inaba M (2011) Cinacalcet HCl suppresses Cyclin D1 oncogene-derived parathyroid cell proliferation in a murine model for primary hyperparathyroidism. Calcif Tissue Int 89:29–35

    Article  CAS  Google Scholar 

  22. Tatsumi R, Komaba H, Kanai G, Miyakogawa T, Sawada K, Kakuta T, Fukagawa M (2013) Cinacalcet induces apoptosis in parathyroid cells in patients with secondary hyperparathyroidism: histological and cytological analyses. Nephron Clin Pract 124:224–231

    Article  CAS  Google Scholar 

  23. Keutgen XM, Buitrago D, Filicori F, Kundel A, Elemento O, Fahey TJ 3rd, Zarnegar R (2012) Calcimimetics versus parathyroidectomy for treatment of primary hyperparathyroidism: retrospective chart analysis of a prospective database. Ann Surg 255:981–985

    Article  Google Scholar 

  24. Nemeth EF, Goodman WG (2016) Calcimimetic and calcilytic drugs: feats, flops, and futures. Calcif Tissue Int 98:341–358

    Article  CAS  Google Scholar 

  25. Rao DS, Honasoge M, Divine GW, Phillips ER, Lee MW, Ansari MR, Talpos GB, Parfitt AM (2000) Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab 85:1054–1058

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Prof. Seiji Fukumoto (Tokushima University) for his great advice concerning the present study. We also thank Ms. Yumi Iriguchi for her secretarial assistance.

Author information

Author notes

  1. Midori Minezaki and Yuichi Takashi contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Chikushino, Japan

    Midori Minezaki, Yuichi Takashi, Kentaro Ochi, Ryo Mitsuoka, Yuka Yamao, Tadachika Kudo, Kunihisa Kobayashi & Ichiro Abe

  2. Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jyonan-ku, Fukuoka City, Fukuoka, 814-0180, Japan

    Yuichi Takashi, Ryo Mitsuoka & Daiji Kawanami

Authors
  1. Midori Minezaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Takashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kentaro Ochi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryo Mitsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuka Yamao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tadachika Kudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daiji Kawanami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kunihisa Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ichiro Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuichi Takashi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Minezaki, M., Takashi, Y., Ochi, K. et al. Reduction in parathyroid adenomas by cinacalcet therapy in patients with primary hyperparathyroidism. J Bone Miner Metab 39, 583–588 (2021). https://doi.org/10.1007/s00774-020-01190-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-020-01190-2

Keywords

Search

Navigation