The ratio of PTH as measured by third and second generation assays as a marker for parathyroid carcinoma
Etienne Cavalier1, Adrian F Daly1, Daniela Betea1, Pierre Delanaye1, Phil Stubbs2, Athur R Bradwell2, Jean-Paul Chapelle1 & Albert Beckers1
Background: Parathyroid carcinoma (PCa) is a rare disease that can be difficult to differentiate initially from benign parathyroid adenoma. PCa over-secrete the amino form of parathyroid hormone (PTH), which is recognized by 3rd generation but not by 2nd generation (intact) PTH assays. In normal individuals, the 3rd generation/2nd generation PTH ratio should always be <1.
Material and methods: We studied the utility of the 3rd generation/2nd generation PTH ratio as a means of distinguishing PCa patients (n=24) from control groups with and without disorders of calcium secretion, including patients on renal hemodialysis (n=73), post-renal transplantation (60), elderly healthy (n=82) and primary hyperparathyroidism (PHP; n=30). 2nd and 3rd generation PTH were assayed with the PTH Duo kit (Scantibodies, Shantee, CA, USA).
Results: The mean 3rd generation/2nd generation PTH ratio was 0.58±0.10 in the dialysis patients, 0.54±0.10 in the renal transplant group, 0.54±0.12 in the elderly healthy patients and 0.68±0.11 in the PHP group. All 245 of these patients presented a 3rd generation/2nd generation PTH ratio of <1. In contrast, we observed an inverted 3rd generation/2nd generation PTH ratio >1 in 20 PCa patients, whereas only 4 PCa patients had a normal ratio of <1.
Conclusions: An inverted 3rd generation/2nd generation PTH ratio occurred in the majority of patients with advanced PCa and was absent in all 245 relevant controls. A 3rd generation/2nd generation PTH ratio >1 had a sensitivity of 83.3% and a specificity of 100% amongst PHP patients as a marker for PCa; among all published cases, the sensitivity was 75.8% and the specificity was 98.9%. This ratio may be useful to identify patients with PCa earlier, and to detect patients either at risk of developing PCa or those in whom recurrence is occurring.