Endocrine Abstracts

Introduction: In Chronic hypoparathyroidism (cHP), secretion of parathyroid hormone (PTH) is insufficient to maintain blood calcium concentration (PCa) steady. More than 70% of cases result from neck surgery and therefore in insufficient secretion of PTH as in mutations of genes involved in PTH synthesis, while mutations of the calcium-sensing receptor (CaSR) and its signaling pathway may result in a remaining secretion of PTH. cHP can exert nephrocalcinosis and/or nephrolithiasis in which calciuria (CaU) may play a key role. If the relationship between PCa and CaU has been studied, very few is known about the determinants of CaU during cHP. Taking advantage of the prospective cohort Epi-Hypo, we designed a study to analyze the determinants of CaU during cHP.

Methods: Epi-Hypo started in 2016 in France and is still actively recruiting. Inclusion criteria are i) chronic (i.e. ≥6 months) hypoPT, ii) followed in France, and iii) agreement to participate. Exclusion criteria are i) transient hypoPT and ii) pseudo-hypoparathyroidism. Both pediatric and adult participants are recruited. Data collected online through a secure digital platform refer to: demographics, circumstances of diagnosis, and follow-up including biology (PCa, CaU, and PTH as its ratio (PTHr) to the upper level of the normal laboratory range).

Results: The database was frozen on March 1st, 2023. At that time, 1,249 patients were included: 893 (71%) were female with median[IQR] age at diagnosis 43[31;56] years. In 937 (73%) patients, the cause was surgery. Nephrolithiasis and/or nephrocalcinosis was diagnosed in 198 (15%) patients over a mean±SD period of 12±10 years of follow-up. We gathered a subpopulation of 768 patients in whom both PCa and CaU (collected in 24-h urine collection) were available at least once. Mean±SD PCa and CaU values were 2.08±0.28 mM and 5.5±4.2 mmol/day, respectively, 33% patients exhibiting hypercalciuria. A positive correlation between PCa and CaU (r²=0.29, P<0.001) and a negative correlation between blood PTH level and CaU (r²=-0.30, P<0.001) were identified. Neither age, gender, or etiology of hypoparathyroidism were significantly different among patients with or without a remaining secretion of PTHr (ie PTHr ≥0.10).

Discussion/Conclusion: Controlling CaU during cHP is a challenging task. For the first time in a large cohort of patients, we report that a remaining secretion of PTH is linked to a lower CaU. Further studies are required to decipher whether this secretion is stable over time and whether it has to be taken into account when treating patients suffering from cHP.