Article Text

Download PDFPDF
Urinary calcium indices in primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH): which test performs best?
  1. Muhammad Fahad Arshad1,2,
  2. James McAllister3,
  3. Azhar Merchant4,
  4. Edmund Rab5,
  5. Jacqueline Cook6,
  6. Richard Eastell2,5,
  7. Sabapathy Balasubramanian2,7
  1. 1 Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  2. 2 The University of Sheffield, Sheffield, UK
  3. 3 The University of Sheffield Medical School, Sheffield, Sheffield, UK
  4. 4 Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
  5. 5 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  6. 6 Sheffield Children’s NHS Foundation Trust, Sheffield, UK
  7. 7 Endocrine Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  1. Correspondence to Muhammad Fahad Arshad, Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; dr.fahadarshad{at}


Aim Primary hyperparathyroidism (PHPT) is much more common than familial hypocalciuric hypercalcaemia (FHH), but there is considerable overlap in biochemical features. Urine calcium indices help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this study was to compare urinary calcium values in patients with PHPT and FHH.

Methods This was a case–control study of patients with PHPT who had successful surgery and genetically proven FHH between 2011 and 2016. Due to low FHH numbers, patients from neighbouring hospitals and outside study period (2017–2019) were allowed to improve power. Data on demographics and urinary calcium were obtained from electronic records and compared between the two groups.

Results During the study period, 250 patients underwent successful PHPT surgery, while in the FHH arm, 19 genetically proven cases were included. The median (IQR) 24-hour urine calcium excretion (UCE) in the PHPT group was 8.3 (5.6–11.2) mmol/24 hours compared with 3.2 (2.1–6.1) mmol/24 hour in the FHH group (p<0.001). Median (IQR) calcium to creatinine clearance ratio (CCCR) in the PHPT and FHH groups was 0.020 (0.013–0.026) and 0.01 (0.002–0.02), respectively (p=0.001). The sensitivity of urinary tests for PHPT was 96% for UCE (cut-off ≥2.5 mmol/24 hour) and 47% for CCCR (cut-off >0.02). The specificity of the urinary tests for FHH was 29.4% for UCE (cut-off <2.5 mmol/24 hour) and 93% for CCCR (cut-off <0.02).

Conclusions 24-hour UCE is more sensitive in diagnosing PHPT; however, it is less specific in ruling out FHH as compared with CCCR, when the cut-offs suggested by the International guidelines from the fourth international workshop are used. A significant proportion of patients with PHPT would have also required genetic studies if the guidelines were followed.

  • Diabetes & endocrinology
  • Calcium & bone

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors Planning of study: SB and MFA. Data collection: MFA, AM and JM. Analysis of data: SB, RE and MFA. Writing manuscript: MFA, SB, JM, ER and JC.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.