Surreal illustration of parathyroid gland intertwined with DNA, symbolizing advanced diagnostic testing.

Decoding Parathyroid Hormone: What the Latest Tests Reveal About Hyperparathyroidism

Beau Callahan in Health & Wellness November 2025 • 4 min read.

"A deeper dive into third-generation PTH assays and their role in diagnosing primary hyperparathyroidism, especially in diverse populations."

Parathyroid hormone (PTH) is the key regulator of calcium levels in our blood. Produced by the parathyroid glands, this 84-amino-acid peptide ensures our nerves, muscles, and bones function correctly. When these glands go into overdrive, they release too much PTH, leading to a condition called hyperparathyroidism.

Diagnosing hyperparathyroidism isn't always straightforward. Over the years, PTH testing has evolved, from the first-generation assays to the more sophisticated second- and third-generation methods. Each generation has its own way of measuring PTH, leading to different results and interpretations.

This article will discuss the advancements in PTH testing, focusing on the third-generation assays and how they compare to the older methods. Drawing on a study conducted in a Brazilian population, we'll explore the nuances of these tests and their implications for diagnosing primary hyperparathyroidism.

PTH Testing: How Third-Generation Assays Improve Diagnosis

Surreal illustration of parathyroid gland intertwined with DNA, symbolizing advanced diagnostic testing.

The earliest PTH tests, known as first-generation assays, had a significant limitation: they couldn't distinguish between the complete PTH molecule (1-84) and its fragments. This meant that individuals with kidney issues, who often have high levels of these fragments, could receive inaccurate PTH readings.

Second-generation assays emerged to address this issue. These tests use two antibodies to target different parts of the PTH molecule, aiming to measure only the intact PTH (1-84). However, even these assays have drawbacks. Studies revealed the existence of PTH fragments that these tests could still detect, leading to potentially inflated PTH levels.

First-Generation Assays: Couldn't differentiate between PTH and its fragments, leading to inaccuracies.
Second-Generation Assays: Aimed to measure intact PTH (1-84) but still detected some fragments.
Third-Generation Assays: Designed to exclusively measure the biologically active PTH (1-84) form.

Enter third-generation assays, also known as Bio-PTH assays. These tests use an antibody that specifically targets the amino-terminal portion of the PTH molecule, ensuring that only the biologically active PTH (1-84) is measured. This specificity is crucial for accurate diagnosis and treatment decisions.

The Future of PTH Testing

As testing methodologies advance, third-generation PTH assays offer promise of more precise assessment, ultimately guiding more effective and personalized treatment strategies. While the findings suggest these tests may not always be superior, their continued refinement and integration with clinical assessments remain vital for optimizing patient care in hyperparathyroidism and related conditions.

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This article is based on research published under:

DOI-LINK: 10.1590/2359-3997000000183, Alternate LINK

Title: Experience With A Third-Generation Parathyroid Hormone Assay (Bio-Pth) In The Diagnosis Of Primary Hyperparathyroidism In A Brazilian Population

Subject: Endocrinology, Diabetes and Metabolism

Journal: Archives of Endocrinology and Metabolism

Publisher: Archives of Endocrinology and Metabolism

Authors: Teresa Cristina P. Bonanséa, Monique Nakayama Ohe, Cynthia Brandão, Cláudia De Francischi Ferrer, Lívia Marcela Santos, Marise Lazaretti-Castro, José Gilberto Henriques Vieira

Published: 2016-10-01

Everything You Need To Know

What is parathyroid hormone (PTH) and why is it important?

Parathyroid hormone, or PTH, is a crucial 84-amino-acid peptide produced by the parathyroid glands. It plays a vital role in regulating calcium levels in the blood, which is essential for the proper functioning of nerves, muscles, and bones. When the parathyroid glands become overactive and release excessive amounts of PTH, it leads to a condition known as hyperparathyroidism. Therefore, understanding PTH and its regulation is critical for understanding hyperparathyroidism and related conditions.

What were the limitations of first-generation PTH assays?

First-generation PTH assays had a significant limitation: they couldn't distinguish between the complete PTH molecule (1-84) and its fragments. This lack of specificity often led to inaccurate PTH readings, especially in individuals with kidney issues who tend to have elevated levels of PTH fragments. The inability to differentiate between whole PTH and its fragments was a major drawback, making the test less reliable.

How do third-generation PTH assays improve the accuracy of hyperparathyroidism diagnosis?

Third-generation assays, also known as Bio-PTH assays, represent an advancement because they specifically target the amino-terminal portion of the PTH molecule. By selectively measuring the biologically active PTH (1-84) form, these assays provide more accurate results. This specificity is crucial for precise diagnosis and treatment decisions in cases of hyperparathyroidism, offering a more reliable assessment compared to earlier testing methods.

What are the drawbacks of second-generation PTH assays, and how do they compare to first-generation assays?

Second-generation PTH assays were designed to measure intact PTH (1-84) by using two antibodies to target different parts of the PTH molecule. However, studies revealed that these assays could still detect certain PTH fragments, leading to potentially inflated PTH levels. Although they aimed to improve upon first-generation assays, they still had limitations in accurately measuring only the complete, active PTH molecule.

What is the future of PTH testing, and how can third-generation assays improve patient care?

While third-generation PTH assays offer the promise of more precise assessment and may not always be superior, their continued refinement and integration with clinical assessments remain vital for optimizing patient care in hyperparathyroidism and related conditions. These advancements in testing methodologies contribute to more effective and personalized treatment strategies, as they can guide healthcare professionals in making informed decisions based on accurate PTH measurements.