Advances in Parathyroid Hormone Testing

Parathyroid hormone (PTH) is an 84 amino acid that plays a key role in phosphocalcic metabolism. Its measurement is essential to diagnose and treat primary hyperparathyroidism and to evaluate chronic kidney disease-mineral and bone disorders (CKD-MBD).  PTH determination is not an easy task, because of the many similar fragments that circulate in our blood. Among these fragments are a group commonly called (7-84) PTH, which are truncated in the amino-terminal part of the peptide. These fragments are quite low in normal healthy subjects; they accumulate in patients with chronic kidney diseases (CKD) and can be up to 50% of the (1-84) PTH in hemodialyzed patients (HD).

Clinical laboratories are often using “intact” PTH assays.  These assays detect the (1-84) peptide and the (7-84) PTH fragments. Because these fragments are recognized differently by the various assays, the values obtained are often very different between “intact” kits. 3rd generation PTH assays, are specific for the (1-84) PTH and do not cross-react with the (7-84) fragments, resulting in less variability.  Up to now, 3rd generation PTH assays have not demonstrated any clinical benefit over intact PTH assays.  However, PTH standardization can be achieved only with 3rd generation and it will be impossible to standardize assays using the intact PTH kits, because of variable cross-reactivities to fragments.

It is important to carefully select the “normal” subjects to establish reference ranges that allow the proper interpretation of the patient’s PTH results. These “normals” should not have secondary hyperparathyroidism and should have eGFR, 25(OH)D, calcium and phosphorus levels within a normal range. Unfortunately, manufacturers have not judiciously selected their “normals”, leading to falsely elevated PTH reference ranges. Using correctly established PTH reference ranges will assist physicians in correctly classifying HD patients in the appropriate bone turnover category.

Learning objectives: 

• To understand the 2nd and 3rd generation PTH assays and their cross-reactivity to different circulating forms
• To understand the importance of good reference range establishment for PTH
• To understand the importance of PTH standardization
• To get up-to-date information regarding PTH stability