Unveiling the complexities of hypoparathyroidism: a comprehensive review of clinical manifestations, diagnosis, and novel therapies

BACKGROUND: Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by insufficient or absent secretion of parathyroid hormone (PTH), which results in hypocalcemia, hyperphosphatemia, and disruption of calcium phosphate homeostasis. Despite advances in understanding its pathophysiology and management, HypoPT remains a complex and impactful condition associated with significant morbidity, impaired quality of life, and long-term complications affecting the skeletal, renal, and neurological systems. METHODS: A literature search was performed on PubMed. Articles were selected based on their relevance to the main topic of the review, with particular attention to recent studies. RESULTS: This review provides a comprehensive synthesis of the current knowledge on HypoPT, addressing its epidemiology, underlying pathophysiological mechanisms, genetic and acquired etiologies, clinical manifestations, diagnostic strategies, and chronic disease-related complications. Emphasis is placed on the genetic spectrum of the disease, challenges of postsurgical management, and burden of conventional therapy, which often fails to fully restore mineral homeostasis and patient well-being. The evolving therapeutic landscape is detailed, highlighting advances from traditional calcium and active vitamin D supplementation to innovative PTH replacement strategies. Among these, palopegteriparatide and eneboparatide (phase 3 clinical trial ongoing) are reshaping treatment paradigms by enabling more physiological restoration of calcium-phosphate balance, reducing complications, and improving patient-centered outcomes, including renal function and quality of life. CONCLUSIONS: By integrating clinical expertise with the latest research developments, this review offers an updated and holistic perspective on HypoPT management, aiming to support clinicians in delivering effective and individualized care to patients across the spectrum of disease severity.