Hypoparathyroidism: translating science from the laboratory to the clinic.

Abstract

Chronic hypoparathyroidism is a rare endocrine disorder characterised by hypocalcaemia due to insufficient parathyroid hormone (PTH) that is associated with a multidimensional reduced quality of life, impairing physical and cognitive functioning, and compromising emotional, psychological, and social wellbeing. This Review integrates recent findings on hypoparathyroidism diagnosis, PTH analogues, calcilytics, preclinical therapeutic agents, parathyroid tissue transplantation, and pluripotent stem cell-based therapies. Emerging diagnostic technologies, including targeted genetic testing, parathyroid autoimmunity assays, and point-of-care calcium monitoring, could enable individualised and real-time management. PTH analogues with extended action (eg, palopegteriparatide, eneboparatide, and canvuparatide) show sustained activation of PTH receptors with reduced requirements for active forms of vitamin D and calcium supplements. Calcilytics (eg, encaleret) normalise calcium-sensing receptor (CaSR) hyperactivation in patients with autosomal dominant hypocalcaemia type 1 and have the potential for broader application in other forms of hypoparathyroidism. Advances in parathyroid regenerative biology with pluripotent stem cells provide platforms for future curative therapies. Progress in parathyroid autotransplantation, allotransplantation, and graft-preservation strategies further expands the therapeutic landscape. Translational research is redefining the future of hypoparathyroidism management. Developments in receptor-targeted therapies, long-acting PTH analogues, negative allosteric modulators of CaSR, and regenerative approaches reflects a shift towards restoring mineral homoeostasis to a more physiological state.