Jean-Philippe Bertocchio1,2,3,4, Muriel Tafflet5, Eugénie Koumakis6, Gérard Maruani1,3,7, Rosa Vargas-Poussou3,4,8, Caroline Silve9,10,11, Peter H Nissen12, Stéphanie Baron1,2,3, Caroline Prot-Bertoye1,2,3,4, Marie Courbebaisse1,2,3,7, Jean-Claude Souberbielle13, Lars Rejnmark14, Catherine Cormier6, Pascal Houillier1,2,3,4,15. 1. Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Département de Physiologie, Paris, France. 2. Université Paris Descartes, Faculté de Médecine, Paris, France. 3. Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Paris, France. 4. INSERM, UMRS1138, Centre de Recherche des Cordeliers, Paris, France. 5. INSERM, U970, Paris Cardiovascular Research Center, University Paris Descartes, Sorbonne Paris Cité, UMR-S970, Paris, France. 6. Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Rhumatologie, Paris, France. 7. Assistance Publique-Hôpitaux de Paris, Institut Necker-Enfants Malades, INSERM U1151 -CNRS UMR 8253, Paris, France. 8. Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France. 9. Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Biochimie et Génétique Moléculaires, Paris, France. 10. INSERM, U1169, Université Paris Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France. 11. Centre de Référence des Maladies Rares du Métabolisme du Phosphore et du Calcium Filière de Santé Maladies Rares OSCAR, Paris, France. 12. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark. 13. Assistance Publique-Hôpitaux de Paris, Institut Necker-Enfants Malades, Laboratoires d'Explorations Fonctionnelles, Paris, France. 14. Department of Endocrinology and Internal Medicine, THG, Aarhus University Hospital, Aarhus C, Aarhus, Denmark. 15. CNRS, ERL8228, Paris, France.
Abstract
Context: Parathyroid-related hypercalcemia is due to primary hyperparathyroidism (PHPT) or to familial hypocalciuric hypercalcemia (FHH). PHPT can lead to complications that necessitate parathyroidectomy. FHH is a rare genetic disease resembling PHPT; surgery is ineffective. A reliable method for distinguishing FHH from PHPT is needed. Objective: To develop an easy-to-use tool to predict if a patient has PHPT. Design: Retrospective analysis of two prospective cohorts. Development of an unsupervised risk equation (Pro-FHH). Setting: University hospitals in Paris, France, and Aarhus, Denmark. Participants: Patients (Paris: 65 with FHH, 85 with PHPT; Aarhus: 38 with FHH, 55 with PHPT) were adults with hypercalcemia and PTH concentration within normal range. Main Outcome Measures: Performance of Pro-FHH to predict PHPT. Results: Pro-FHH takes into account plasma calcium, PTH, and serum osteocalcin concentrations, and calcium-to-creatinine clearance ratio calculated from 24-hour urine collection (24h-CCCR). In the Paris cohort, area under the receiver operating characteristic curve (AUROC) of Pro-FHH was 0.961, higher than that of 24h-CCCR. With a cutoff value of 0.928, Pro-FHH had 100% specificity and 100% positive predictive value for the diagnosis of PHPT; it correctly categorized 51 of 85 patients with PHPT; the remaining 34 were recommended to undergo genetic testing. No patients with FHH were wrongly categorized. In an independent cohort from Aarhus, AUROC of Pro-FHH was 0.951, higher than that of 24h-CCCR. Conclusion: Pro-FHH effectively predicted whether a patient has PHPT. A prospective trial is necessary to assess its usefulness in a larger population and in patients with elevated PTH concentration.
Context:Parathyroid-related hypercalcemia is due to primary hyperparathyroidism (PHPT) or to familial hypocalciuric hypercalcemia (FHH). PHPT can lead to complications that necessitate parathyroidectomy. FHH is a rare genetic disease resembling PHPT; surgery is ineffective. A reliable method for distinguishing FHH from PHPT is needed. Objective: To develop an easy-to-use tool to predict if a patient has PHPT. Design: Retrospective analysis of two prospective cohorts. Development of an unsupervised risk equation (Pro-FHH). Setting: University hospitals in Paris, France, and Aarhus, Denmark. Participants: Patients (Paris: 65 with FHH, 85 with PHPT; Aarhus: 38 with FHH, 55 with PHPT) were adults with hypercalcemia and PTH concentration within normal range. Main Outcome Measures: Performance of Pro-FHH to predict PHPT. Results: Pro-FHH takes into account plasma calcium, PTH, and serum osteocalcin concentrations, and calcium-to-creatinine clearance ratio calculated from 24-hour urine collection (24h-CCCR). In the Paris cohort, area under the receiver operating characteristic curve (AUROC) of Pro-FHH was 0.961, higher than that of 24h-CCCR. With a cutoff value of 0.928, Pro-FHH had 100% specificity and 100% positive predictive value for the diagnosis of PHPT; it correctly categorized 51 of 85 patients with PHPT; the remaining 34 were recommended to undergo genetic testing. No patients with FHH were wrongly categorized. In an independent cohort from Aarhus, AUROC of Pro-FHH was 0.951, higher than that of 24h-CCCR. Conclusion: Pro-FHH effectively predicted whether a patient has PHPT. A prospective trial is necessary to assess its usefulness in a larger population and in patients with elevated PTH concentration.
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