PMID- 38214877 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20240315 IS - 1559-0100 (Electronic) IS - 1355-008X (Print) IS - 1355-008X (Linking) VI - 83 IP - 3 DP - 2024 Mar TI - Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia. PG - 747-756 LID - 10.1007/s12020-023-03560-y [doi] AB - OBJECTIVE: Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. DESIGN: Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes. METHODS: Clinical, biochemical, radiological and treatment data were collected. We established a prediction model for the identification of FHH-positive cases by logistic regression analysis and area under the ROC curve (AUROC) was estimated. RESULTS: We included 66 index cases, of which 30 (45.5%) had a pathogenic variant. FHH-positive cases were younger (p = 0.029), reported more frequently a positive family history (p < 0.001), presented higher magnesium (p < 0.001) and lower parathormone levels (p < 0.001) and were less often treated for hypercalcemia (p = 0.017) in comparison to FHH-negative cases. Magnesium levels showed the highest AUROC (0.825, 95%CI: 0.709-0.941). The multivariate analysis revealed that family history and magnesium levels were independent predictors of a positive genetic result. The predictive model showed an AUROC of 0.909 (95%CI: 0.826-0.991). CONCLUSIONS: The combination of magnesium and a positive family history offered a good diagnostic accuracy to predict a positive genetic result. Therefore, the inclusion of magnesium measurement in the routine evaluation of patients with suspected FHH might provide insight into the identification of a positive genetic result of any of the CaSR-related genes. CI - (c) 2023. The Author(s). FAU - Asla, Queralt AU - Asla Q AUID- ORCID: 0000-0001-6049-8048 AD - Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Sant Pau Biomedical Research Institute (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Medicine, University of Vic-Central University of Catalonia, Vic, Spain. FAU - Sarda, Helena AU - Sarda H AUID- ORCID: 0000-0002-0138-8217 AD - Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Sant Pau Biomedical Research Institute (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Segui, Nuria AU - Segui N AD - Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain. FAU - Martinez de Pinillos, Guillermo AU - Martinez de Pinillos G AD - Department of Endocrinology, Hospital Universitario Virgen de Valme, Sevilla, Spain. FAU - Mazarico-Altisent, Isabel AU - Mazarico-Altisent I AUID- ORCID: 0000-0001-9651-7650 AD - Department of Endocrinology and Nutrition, Hospital Universitari Parc Tauli, Sabadell, Barcelona, Spain. AD - Institut d'Investigacio i Innovacio Parc Tauli (I3PT), Sabadell, Barcelona, Spain. FAU - Capel, Ismael AU - Capel I AD - Department of Endocrinology and Nutrition, Hospital Universitari Parc Tauli, Sabadell, Barcelona, Spain. AD - Institut d'Investigacio i Innovacio Parc Tauli (I3PT), Sabadell, Barcelona, Spain. FAU - Rives, Jose AU - Rives J AD - Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. FAU - Suarez, Javier AU - Suarez J AD - Department of Endocrinology and Nutrition, Hospital Arnau de Vilanova, Lleida, Spain. FAU - Avila-Rubio, Veronica AU - Avila-Rubio V AD - Department of Endocrinology and Nutrition, Hospital Universitario Clinico San Cecilio, Granada, Spain. AD - Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), 18014, Granada, Spain. FAU - Munoz Torres, Manuel AU - Munoz Torres M AUID- ORCID: 0000-0002-9645-3260 AD - Department of Endocrinology and Nutrition, Hospital Universitario Clinico San Cecilio, Granada, Spain. AD - Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), 18014, Granada, Spain. AD - CIBER on Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, 28029, Madrid, Spain. FAU - Saigi, Ignasi AU - Saigi I AD - Department of Medicine, University of Vic-Central University of Catalonia, Vic, Spain. AD - Department of Endocrinology and Nutrition, Hospital Universitari de Vic, Vic, Spain. FAU - Palacios, Nuria AU - Palacios N AUID- ORCID: 0000-0001-7366-2476 AD - Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain. FAU - Urgell, Eulalia AU - Urgell E AD - Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. FAU - Webb, Susan M AU - Webb SM AUID- ORCID: 0000-0001-7052-6436 AD - Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Sant Pau Biomedical Research Institute (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Medicine, Universitat Autonoma de Barcelona, Bellaterra, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBER-ER, Unit 747), ISCIII, Madrid, Spain. FAU - Fernandez, Merce AU - Fernandez M AD - Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau - Hospital Dos de Maig, Barcelona, Spain. FAU - Oriola, Josep AU - Oriola J AD - Department of Biochemistry and Molecular Genetic, CDB, Hospital Clinic, Barcelona, Spain. AD - Institut d'Investigacions Biomediques Pi i Sunyer (IDIBAPS), Barcelona, Spain. AD - Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. FAU - Mora, Mireia AU - Mora M AUID- ORCID: 0000-0002-5887-5016 AD - Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain. AD - Institut d'Investigacions Biomediques Pi i Sunyer (IDIBAPS), Barcelona, Spain. AD - Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. FAU - Tondo, Mireia AU - Tondo M AUID- ORCID: 0000-0002-0301-9984 AD - Sant Pau Biomedical Research Institute (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. FAU - Aulinas, Anna AU - Aulinas A AUID- ORCID: 0000-0002-1205-7114 AD - Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. aaulinas@santpau.cat. AD - Sant Pau Biomedical Research Institute (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. aaulinas@santpau.cat. AD - Department of Medicine, University of Vic-Central University of Catalonia, Vic, Spain. aaulinas@santpau.cat. AD - Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBER-ER, Unit 747), ISCIII, Madrid, Spain. aaulinas@santpau.cat. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20231030 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - I38ZP9992A (Magnesium) RN - Hypocalciuric hypercalcemia, familial, type 1 SB - IM MH - Humans MH - *Hypercalcemia/diagnosis/genetics/*congenital MH - Retrospective Studies MH - Magnesium MH - Prospective Studies MH - *Hyperparathyroidism, Primary/diagnosis PMC - PMC10901938 OTO - NOTNLM OT - CASR gene OT - CASR mutations OT - Familial hypocalciuric hypercalcemia (FHH) OT - calcium disorders OT - calcium-sensing receptor (CaSR) OT - primary hyperparathyroidism (PHPT) COIS- The authors declare no competing interests. EDAT- 2024/01/12 12:41 MHDA- 2024/03/01 06:44 PMCR- 2023/10/30 CRDT- 2024/01/12 11:13 PHST- 2023/05/07 00:00 [received] PHST- 2023/10/02 00:00 [accepted] PHST- 2024/03/01 06:44 [medline] PHST- 2024/01/12 12:41 [pubmed] PHST- 2024/01/12 11:13 [entrez] PHST- 2023/10/30 00:00 [pmc-release] AID - 10.1007/s12020-023-03560-y [pii] AID - 3560 [pii] AID - 10.1007/s12020-023-03560-y [doi] PST - ppublish SO - Endocrine. 2024 Mar;83(3):747-756. doi: 10.1007/s12020-023-03560-y. Epub 2023 Oct 30.