What is intact Parathyroid Hormone (PTH)?

Intact Parathyroid Hormone (PTH)

Intact PTH refers to a laboratory measurement that detects the biologically active 84-amino acid parathyroid hormone molecule using immunoradiometric assay (IRMA) or immunochemiluminometric assay (ICMA) techniques. 1

Definition and Structure

• Intact PTH assays (second-generation) use a sandwich immunoassay with two antibodies - one directed against the C-terminal part and another against the N-terminal part of the PTH molecule 1
• These assays were designed to measure only full-length PTH (1-84), but they also detect biologically inactive fragments, particularly the 7-84 PTH fragment 1
• The biologically active portion of PTH resides primarily in the N-terminal region, particularly in amino acid residues 1-7 1

Clinical Significance

• Intact PTH measurement is an adequate screening tool to differentiate between high-turnover bone disease (osteitis fibrosa) and low-turnover bone disorders (adynamic bone disease) in chronic kidney disease (CKD) 1
• PTH is a critical regulator of extracellular calcium and phosphate homeostasis 2
• It enhances calcium reabsorption while inhibiting phosphate reabsorption in the kidneys 3
• PTH increases the synthesis of 1,25-dihydroxyvitamin D, which increases gastrointestinal calcium absorption 3, 4
• It increases bone resorption to release calcium and phosphate into circulation 4

Limitations of Intact PTH Assays

• Second-generation (intact PTH) assays overestimate biologically active PTH by detecting C-terminal fragments missing amino acids from the N-terminus 1
• The 7-84 PTH fragment is particularly problematic as it lacks biological activity but is measured by intact PTH assays 1
• Post-translational modifications of PTH (oxidation, phosphorylation) can affect its biological activity but may still be detected by intact PTH assays 1
• This can lead to spurious elevations in PTH levels in CKD patients who may not have significant hyperparathyroid bone disease despite elevated PTH levels 1

Newer PTH Assays

• Third-generation assays (whole or bio-intact PTH assays) use an N-terminal antibody directed against the first four amino acids of PTH, making them more specific 1
• These newer assays only measure full-length PTH and do not detect fragments such as 7-84 PTH 1
• However, third-generation assays can still detect posttranslationally modified PTH forms 1
• PTH measurements by second- and third-generation assays can vary up to 47%, which is important to consider when interpreting results 1

Clinical Applications

• Serum levels of calcium, phosphorus, and intact PTH should be measured in all patients with CKD and GFR <60 mL/min/1.73 m² 1
• The frequency of these measurements should be based on the stage of CKD 1
• Target ranges for intact PTH vary by CKD stage, as normal ranges are not appropriate for CKD patients 1
• In primary hyperparathyroidism, intact PTH measurement is superior to the measurement of midregional fragments for diagnosis 5

Important Considerations

• When interpreting intact PTH results, clinicians should be aware of which generation of assay is being used 1
• Attempting to maintain intact PTH levels of CKD patients in the "normal" range below 65 pg/mL can lead to adynamic bone disease 1
• The current recommendations distinguish between the "desired target range" for intact PTH in CKD patients and the "normal range" determined for patients with normal kidney function 1

Intact PTH measurement remains a valuable tool in clinical practice, particularly for the diagnosis and management of disorders affecting calcium-phosphate homeostasis, despite its limitations in detecting biologically inactive fragments.