Ricerca Progetti nazionali, regionali, internazionaliNAZIONALIPRIN 2022Primary parathyroid hormone deficiency

Primary parathyroid hormone deficiency and resistance: focus on alterations of phosphate and magnesium metabolism and their impact on clinical outcomes: the PARAPHOSPH study

The PARAPHOSPH study aims to elucidate poorly investigated aspects of hypoparathyroidism and pseudohypoparathyroidism, invalidating metabolic disorders deriving from a PTH-deficient or resistant state, in order to improve diagnosis, management and follow-up, thus paving the way to the development of novel biomarkers and therapeutic approaches, as well as extending the current knowledge on the parathyroid-bone-kidney axis. Despite the growing interest on hypocalcemic disorders, several areas of the etiopatho-physiology and long-term complications require more research. It is increasingly evident that the complex clinical picture in hypoparathyroidism is not ensuing from the lack of calcium itself. A possible role has been attributed to the lack of PTH, so that replacement therapy with the missing enzyme has been advocated to restore a normal metabolism and increase overall health. The coexistent mineral abnormalities, i.e. hyperphosphatemia and hypomagnesemia, have received only partial attention but they could explain and contribute to general manifestation of the disease. In addition, hypoparathyroidism, being a high-phosphate disease, could serve, in parallel to the deeply studied chronic kidney diseases-mineral bone disorder, as a model to elucidate in vivo the possible roles of high phosphate in the pathogenesis and maintenance of cardiovascular alterations. In hypoparathyroidism, high phosphate levels are often not corrected by either conventional therapy with calcitriol and calcium salts or specific replacement therapy with PTH 1-84. Both serum phosphate and magnesium have not been included in the evaluation of quality of life. So far, no study has focused on all the abnormalities in mineral metabolism and explored their impact on the different manifestations of the disease, and, in particular, on cardiovascular manifestations. The impact of altered phosphate metabolism on disease burden has not been assessed. Extracellular magnesium is often altered in hypoparathyroidism and small alterations may contribute to the poor control of the disease. A low magnesium state can worsen symptoms but, at the same time, may concur to increase cardiovascular disease burden in these patients and decrease overall sense of well-being. Extracellular ionized magnesium has never been assessed in hypoparathyroidism and its alterations might explain the scares disease control even in the face of normal extracellular calcium. With this respect, the PARAPHOSPH study will focus on: i) newly observed cardiovascular alterations in both PTH-deficient and -resistant patients; ii) the impact of phosphate levels on therapy-associated and disease-associated complications; iii) the elucidation of PTH and FGF23 relationship in mineral homeostasis; iv) the molecular determinants of ectopic ossification in PTH-resistant patients; v) the impact of extracellular magnesium on quality of life, disease burden and its possible role in cardiovascular manifestations.

 

Data di avvio 18 Ottobre 2023

Data di completamento 18 Ottobre 2025

Total cost  € 107232,00

 

Progetto 2022B5HC29 finanziato all’interno del Bando PRIN 2022 di cui al Decreto Direttoriale n. 104 del 02/02/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23021360006