Cinacalcet in the management of primary hyperparathyroidism

Abstract

Parathyroidectomy is currently the only curative treatment for primary hyperparathyroidism (PHPT). There are few alternative treatment options in patients who are ineligible for, or unwilling to undergo, surgery and those in whom parathyroidectomy has failed. Current options include the recently approved drug cinacalcet. Cinacalcet is an allosteric modulator of the calcium-sensing receptor, acting to sensitize this receptor to extracellular calcium. Cinacalcet has been found to be effective in reducing or normalizing serum calcium levels in several groups of PHPT patients, including those with mild-to-moderate PHPT, intractable disease, parathyroid carcinoma and multiple endocrine neoplasia Type 1. Cinacalcet slightly reduces parathyroid hormone levels and has no effect on bone mineral density. Cinacalcet is well tolerated when used at low doses, but side effects are not uncommon when relatively high doses are needed to control hypercalcemia. The current evidence indicates that cinacalcet may be of benefit in a wide spectrum of PHPT severities, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. It is presently unknown how much of the biochemical benefit of cinacalcet treatment translates into a clinical benefit, particularly in patients with mild-to-moderate hypercalcemia. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT.

Keywords::

• calcium-sensing receptor
• hypercalcemia
• parathyroid carcinoma
• persistent primary hyperparathyroidism

Financial & competing interests disclosure

C Marcocci is a consultant and a speaker for Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^†High-fat meal increases C_max by 82%.

C_max: Peak serum concentration after administration of a drug; T_½: Time required to reach the half maximum serum concentration; T_max: Time after administration of a drug when the maximum serum concentration is obtained.

Modified with permission from [16].

^†Defined as primary hyperparathyroidism unresolved after parathyroidectomy or with contraindications to parathyroidectomy.