What is the role of the parathyroid (PTH) gland and what is the difference between parathyroid hormone (PTH) and intact parathyroid hormone (iPTH)?

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Role of Parathyroid and Difference Between PTH and Intact PTH

The parathyroid glands are essential endocrine organs primarily responsible for calcium and phosphate homeostasis through the secretion of parathyroid hormone (PTH), while intact PTH (iPTH) specifically refers to the biologically active 84-amino acid form measured in clinical assays to distinguish it from inactive PTH fragments that accumulate especially in kidney disease. 1

Role of the Parathyroid Glands

The parathyroid glands play a crucial role in maintaining calcium and phosphate balance through several mechanisms:

Calcium Regulation

  • Calcium sensing: Parathyroid chief cells detect hypocalcemia via calcium-sensing receptors (CaSR) on their surface 1
  • PTH secretion: When serum calcium decreases, the parathyroid glands secrete PTH to restore normal levels
  • Target organs: PTH acts on three primary target organs:
    1. Bone: Stimulates release of calcium and phosphate from bone into circulation
    2. Kidneys: Increases calcium reabsorption and phosphate excretion
    3. Intestine (indirect): Stimulates 1-α-hydroxylase (CYP27B1) to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, which enhances intestinal calcium absorption 1

Phosphate Regulation

  • PTH decreases phosphate reabsorption in the renal tubules, increasing phosphate excretion
  • This action helps maintain normal phosphate levels despite increased bone resorption 1

Interaction with Other Hormones

  • FGF23: Works with PTH to regulate phosphate; FGF23 is released in response to high phosphate, PTH, and 1,25-dihydroxyvitamin D
  • Vitamin D: PTH stimulates the production of active vitamin D, which provides negative feedback to the parathyroid glands 1

Difference Between PTH and Intact PTH

PTH Synthesis and Structure

  • PTH is synthesized as a 115-amino acid precursor (pre-proPTH)
  • Pre-proPTH is cleaved to proPTH, then to the biologically active 84-amino acid PTH 1
  • The first 34 amino acids and alpha helix formation are crucial for biological activity 1

PTH Fragments

  • After secretion, PTH circulates in multiple forms:
    1. Full-length (1-84) PTH: The biologically active form with a short half-life (2-4 minutes)
    2. C-terminal fragments: Mostly inactive fragments with longer half-lives (5-10 times longer than full-length PTH) 1

Intact PTH (iPTH) vs. PTH

  • Intact PTH (iPTH): Refers specifically to the biologically active 84-amino acid form of PTH
  • PTH: General term that can include both the intact hormone and its various fragments 1

Clinical Significance of the Distinction

  • In patients with normal kidney function, the distinction is less critical
  • In kidney disease, C-terminal fragments accumulate due to reduced renal clearance, making the distinction crucial 1
  • iPTH assays (second-generation) were developed to measure only the biologically active form, distinguishing it from inactive fragments 1

Measurement Methods

  • First-generation assays: Measured both active PTH and inactive fragments
  • Second-generation assays (intact PTH): More specific, designed to measure only the biologically active form
  • Third-generation assays: Even more specific, measuring only the whole PTH molecule 1

Clinical Implications

In Chronic Kidney Disease

  • As kidney function declines, C-terminal PTH fragments accumulate
  • iPTH measurement becomes critical for accurate assessment of parathyroid function
  • Guidelines for chronic kidney disease recommend monitoring iPTH rather than total PTH 1

In Hyperparathyroidism

  • iPTH is essential for diagnosing primary hyperparathyroidism, especially normocalcemic variants
  • In secondary hyperparathyroidism, iPTH helps guide treatment decisions, including when to start medications like cinacalcet 1, 2

Intraoperative Use

  • During parathyroid surgery, rapid iPTH measurement can confirm successful removal of abnormal parathyroid tissue, though it has limitations 3

Common Pitfalls in PTH Interpretation

  • Assay variability: Different laboratories may use different assays, leading to different results
  • Kidney function: Always interpret PTH/iPTH in the context of the patient's kidney function
  • Vitamin D status: Low vitamin D can cause secondary hyperparathyroidism
  • Medications: Some medications (like cinacalcet) directly affect PTH levels 2
  • Standardization issues: Lack of standardization between assays can lead to significant differences in measured values 1

Understanding the distinction between PTH and iPTH is crucial for accurate diagnosis and management of disorders of calcium and phosphate metabolism, particularly in patients with kidney disease.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Research

Limited role for intraoperative intact PTH measurement in parathyroid surgery.

Annals of the Royal College of Surgeons of England, 1995

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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