title: Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods.
abstract: BACKGROUND
  Familial hypocalciuric hypercalcaemia (FHH) must be differentiated from primary hyperparathyroidism (PHPT) because prognosis and treatment differ. In daily practice this discrimination is often based on the renal calcium excretion or the calcium/creatinine clearance ratio (CCCR). However, the diagnostic performance of these variables is poorly documented.
  
  
  OBJECTIVE
  To appraise the power of various simple biochemical variables to differentiate between FHH and PHPT using calcium sensing receptor (CASR) gene analysis and histopathological findings as gold standards.
  
  
  METHODS
  Follow-up approach (direct design).
  
  
  METHODS
  We included 54 FHH patients (17 males and 37 females, aged 18-75 years) with clinically significant mutations in the CASR gene and 97 hypercalcaemic patients with histologically verified PHPT (17 males and 80 females, aged 19-86 years). All PHPT patients became normocalcaemic following successful neck exploration.
  
  
  RESULTS
  Based on receiver operating characteristic (ROC) curve analysis, the CCCR was only marginally better, as judged by the area under curve (AUC = 0.923 +/- 0.021 (SE)), than the 24-h calcium/creatinine excretion ratio (AUC = 0.903 +/- 0.027) and the 24-h calcium excretion (AUC = 0.876 +/- 0.029). However, overlap performance analysis disclosed that the CCCR included fewer patients with PHPT together with the FHH patients than the other two variables at different cut-off points. Based on the ROC curve, the optimal cut-off point for diagnosing FHH using CCCR was < 0.0115, which yielded a diagnostic specificity of 0.88 and a sensitivity of 0.80. Overlap analysis revealed that a cut-off point for CCCR at < 0.020 would sample 98% (53/54) of all patients with FHH and include 35% (34/97) of the PHPT patients.
  
  
  CONCLUSIONS
  Our results support the use of the CCCR as an initial screening test for FHH. We suggest a two-step diagnostic procedure, where the first step is based on the CCCR with a cut-off at < 0.020, and the second step is CASR gene analysis in patients with FHH or PHPT.
authors.affiliation: Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus, Denmark. rlg06sec@as.aaa.dk
authors.forename: Signe Engkjaer
authors.initials: SE
authors.lastname: Christensen
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
authors.forename: Lene
authors.initials: L
authors.lastname: Heickendorff
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism / Q000652:urine*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006305:Health Status Indicators; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium