Thomas Cuny

Context Familial hypocalciuric hypercalcemia type 1 (FHH-1) defines an autosomal dominant disease, related to mutations in the CASR gene, with mild hypercalcemia in most cases. Cases of FHH-1 with a short QT interval have not been reported to date. Objective Three family members presented with FHH-1 and short QT interval (<360 ms), a condition that could lead to cardiac arrhythmias, and the effects of cinacalcet, an allosteric modulator of the CaSR, in rectifying the abnormal sensitivity of the mutant CaSR and in correcting the short QT interval were determined. Methods CASR mutational analysis was performed by next-generation sequencing and functional consequences of the identified CaSR variant (p.Ile555Thr), and effects of cinacalcet were assessed in HEK293 cells expressing wild-type and variant CaSRs. A cinacalcet test consisting of administration of 30 mg cinacalcet (8 Am) followed by hourly measurement of serum calcium, phosphate, and parathyroid hormone during 8 hours and an electrocardiogram was performed. Results The CaSR variant (p.Ile555Thr) was confirmed in all 3 FHH-1 patients and was shown to be associated with a loss of function that was ameliorated by cinacalcet. Cinacalcet decreased parathyroid hormone by >50% within two hours, and decreases in serum calcium and increases in serum phosphate occurred within 8 hours, with rectification of the QT interval, which remained normal after 3 months of cinacalcet treatment. Conclusion Our results indicate that FHH-1 patients should be assessed for a short QT interval and a cinacalcet test used to select patients who are likely to benefit from this treatment.

Acromegaly is a rare and insidious disease characterized by chronic excess growth hormone, leading to various morphological changes and systemic complications. Despite its low prevalence, acromegaly poses a significant socioeconomic burden on patients and healthcare systems. This review synthesizes the current state of knowledge on the psychosocial burden, disability, impact on daily life, and cost of acromegaly disease, focusing on the quality of life, partnership, medical care and treatment afflictions, participation in daily activities, professional and leisure impairment, and cost of treatment for acromegaly and its comorbidities. It also examines management strategies, coping mechanisms, and interventions aimed at alleviating this burden. A comprehensive understanding of the extent of the socioeconomic burden in acromegaly is crucial to develop effective strategies to improve treatment and care. Further research is warranted to explore the myriad factors contributing to this burden, as well as the efficacy of interventions to alleviate it, ultimately enhancing the quality of life for patients with acromegaly.