Pro-FHH: A Risk Equation to Facilitate the Diagnosis of Parathyroid-Related Hypercalcemia

• Published in: The journal of clinical endocrinology and metabolism 2018-07, Vol.103 (7), p.2534-2542
• Main Authors: Bertocchio, Jean-Philippe, Tafflet, Muriel, Koumakis, Eugénie, Maruani, Gérard, Vargas-Poussou, Rosa, Silve, Caroline, Nissen, Peter H, Baron, Stéphanie, Prot-Bertoye, Caroline, Courbebaisse, Marie, Souberbielle, Jean-Claude, Rejnmark, Lars, Cormier, Catherine, Houillier, Pascal
• Format: Article
• Language: English
• Subjects: Adult; Aged; Area Under Curve; Calcium; Calcium - blood; Calcium - urine; Creatinine; Creatinine - urine; Diagnosis; Female; Genetic screening; Humans; Hypercalcemia; Hypercalcemia - complications; Hypercalcemia - congenital; Hypercalcemia - diagnosis; Hypercalcemia - etiology; Hyperparathyroidism; Hyperparathyroidism, Primary - complications; Hyperparathyroidism, Primary - diagnosis; Life Sciences; Male; Middle Aged; Osteocalcin; Osteocalcin - blood; Parathyroid; Parathyroid hormone; Parathyroid Hormone - blood; Parathyroidectomy; Patients; Predictive Value of Tests; Retrospective Studies; Risk Assessment - methods; ROC Curve; Sensitivity and Specificity; Surgery
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2017-02773

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. To develop an easy-to-use tool to predict if a patient has PHPT. Retrospective analysis of two prospective cohorts. Development of an unsupervised risk equation (Pro-FHH). University hospitals in Paris, France, and Aarhus, Denmark. 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. Performance of Pro-FHH to predict PHPT. 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. 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.