The following is a summary of “Cinacalcet Reverses Short QT Interval in Familial Hypocalciuric Hypercalcemia Type 1,” published in the February 2024 issue of Endocrinology by Cuny, et al.

Familial hypocalciuric hypercalcemia type 1 (FHH-1) is characterized by autosomal dominant inheritance and is associated with mutations in the CASR gene, resulting in mild hypercalcemia in most cases. However, cases of FHH-1 presenting with a short QT interval have not been previously reported. For a study, researchers sought to investigate three family members presenting with FHH-1 and a short QT interval (<360 ms), a condition that may predispose individuals to cardiac arrhythmias. They assessed the effects of cinacalcet, an allosteric modulator of the CaSR, in rectifying the abnormal sensitivity of the mutant CaSR and correcting the short QT interval.

CASR mutational analysis was conducted using next-generation sequencing, and the functional consequences of the identified CaSR variant (p.Ile555Thr) were evaluated in HEK293 cells expressing wild-type and variant CaSRs. A cinacalcet test involving the administration of 30 mg cinacalcet at 8 AM, followed by hourly measurements of serum calcium, phosphate, and parathyroid hormone over 8 hours, along with an electrocardiogram, was performed.

The CaSR variant (p.Ile555Thr) was confirmed in all three FHH-1 patients and was associated with a loss of function that was improved by cinacalcet treatment. Cinacalcet led to a decrease in parathyroid hormone levels by >50% within two hours, accompanied by reductions in serum calcium and increases in serum phosphate within 8 hours. Notably, cinacalcet treatment resulted in the normalization of the QT interval, which remained within the normal range after 3 months of therapy.

The findings suggested that FHH-1 patients should be evaluated for a short QT interval, and a cinacalcet test could aid in identifying patients likely to benefit from the treatment.

Reference: academic.oup.com/jcem/article-abstract/109/2/549/7246602