The third/second generation PTH assay ratio as a marker for parathyroid carcinoma: evaluation using an automated platform

J Clin Endocrinol Metab. 2014 Mar;99(3):E453-7. doi: 10.1210/jc.2013-3730. Epub 2013 Jan 1.


Background: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal 3rd/2nd generation PTH ratio (<1) is inverted in PCa (ie, >1).

Objective: The objective of the investigation was to study the utility and advantages of automated 3rd/2nd generation PTH ratio measurements using the Liaison XL platform over existing manual techniques.

Setting: The study was conducted at a tertiary-referral academic center.

Design: This was a retrospective laboratory study.

Subjects: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with primary-hyperparathyroidism (n = 144; mean age 53.8 y), renal transplantation (n = 41; mean age 50.6 y), hemodialysis (n = 80; mean age 65.2 y), and healthy elderly subjects (n = 40; mean age 72.6 y).

Results: The median (interquartile range) 3rd/2nd generation PTH ratio was 1.16 (1.10-1.38) in the PCa group, which was significantly higher than the control groups: hemodialysis: 0.74 (0.71-0.75); renal transplant: 0.77 (0.73-0.79); primary hyperparathyroidism: 0.76 (0.74-0.78); healthy elderly: 0.80 (0.74-0.83). An inverted 3rd/2nd-generation PTH ratio (>1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%): 3 of 80 hemodialysis (3.8%), and 4 of 144 primary-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted 3rd/2nd-generation PTH ratio with the automated method.

Conclusions: Study of the 3rd/2nd-generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted 3rd/2nd-generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%).

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Automation, Laboratory
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / blood
  • Case-Control Studies
  • Female
  • Humans
  • Immunoassay / instrumentation
  • Immunoassay / methods
  • Luminescent Measurements / instrumentation
  • Luminescent Measurements / methods
  • Male
  • Middle Aged
  • Parathyroid Hormone / analysis*
  • Parathyroid Hormone / blood
  • Parathyroid Neoplasms / blood
  • Parathyroid Neoplasms / diagnosis*
  • Retrospective Studies


  • Biomarkers, Tumor
  • Parathyroid Hormone