ESPE2023 Poster Category 1 Adrenals and HPA Axis (40 abstracts)
Nephrocalcinosis: an emerging issue in children with Congenital Adrenal Hyperplasia
Mariangela Chiarito 1 , Crescenza Lattanzio 1 , Vito D'Ascanio 2 , Donatella Capalbo 3 , Paolo Cavarzere 4 , Anna Grandone 5 , Caterina Luongo 5 , Giorgia Pepe 6 , Malgorzata Wasniewska 6 , Thomas Zoller 4 , Mariacarolina Salerno 7 & Maria Felicia Faienza 8
1University A. Moro of Bari, Bari, Italy. 2Institute of Sciences of Food Production (ISPA), Italian National Research Council (CNR), Bari, Italy. 3Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy. 4Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy. 5Department of the Woman, of the Child, of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy. 6Department of Human Pathology of adulthood and childhood, University of Messina, Messina, Italy. 7Pediatric Endocrinology Unit-Department of Translational Medical Sciences, University of Naples Federico II and University Hospital Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy. 8Department of Precision and Regenerative Medicine and Ionian Area, University A. Moro, Bari., Bari, Italy
Hypercalcemia and nephrocalcinosis (NC) are rare findings associated with congenital adrenal hyperplasia (CAH), whose pathogenetic mechanisms are still unclear. In this study we aimed to investigate the prevalence of NC in a cohort of Italian children affected with classical form of CAH, and to correlate its association with metabolic control of the disease.
Subjects and Methods: This is a multicenter one year-perspective study involving five Italian Pediatric Endocrinology Centers. The study population included 52 subjects (35 males) with molecular diagnosis of CAH evaluated at three different time-points: T0, T1 (+ 6 months), T2 (+12 months). At each follow-up visit, ACTH, 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and Ca/Cr ratio in urine were measured. A renal ultrasound was also performed. A multivariate statistical approach using principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time.
Results: The prevalence of NC was 17.3% (9 subjects) at T0, 13.5% (7 subjects) at T1 and 11.5% (6 subjects) at T2. A statistically significant difference was found for 17-OHP [T0: 11.1 (3.0∼25.1), T1: 7.1 (1.8∼19.9), T2: 5.9 (2.0∼20.0), P<0.005] and for Δ4-androstenedione [T0: 0.9 (0.3∼2.5), T1: 0.3 (0.3∼1.1), T2: 0.5 (0.3∼1.5), P<0.05] which both decreased over the follow up time. No statistically significant difference was found in the mean values of the Ca/Cr ratio [T0: 0.08 (0.05∼0.16), T1: 0.11 (0.05∼0.17), T2: 0.09 (0.06∼0.18)], and ACTH [T0: 58.5(16.0∼195.5), T1: 57.7 (14.6∼187.5), T2: 35.0 (16.0∼116.2)], even if for the latter a downward trend was observed. PCA highlighted two strong correlation patterns among 17-OHP, Δ4-androstenedione and ACTH, and among DHEAS and Ca/Cr. Interestingly, a trend over time was observed along the negative directions of PC1 and PC2, moving from the first time point (T0) to the end point (T2). In these directions, the loading plot revealed a decrease of the 17-OHP, Δ4-androstenedione and ACTH variables amount, so these results suggested that these variables decrease during the follow up.
Conclusions: NC represents an important issue related to CAH. The decrease of 17-OHP, Δ4-androstenedione and ACTH levels, matched with the decrease in the NC prevalence during the follow up, could suggest that an accurate metabolic control of the disease is pivotal to prevent this complication. More studies are needed to clarify pathogenesis and to detect risk factors.
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