Overview
Intact Parathyroid Hormone (Intact PTH) is a polypeptide hormone secreted by the chief cells of the parathyroid glands. It plays a central role in regulating calcium and phosphorus metabolism and is critical for maintaining calcium homeostasis in the body. PTH has a very short half-life of approximately four minutes, which allows rapid adjustment of calcium levels in response to physiological needs.
The parathyroid gland secretes two major fragments of parathyroid hormone, namely 1–84 PTH and 7–84 PTH. The intact PTH assay detects both these fragments, whereas whole PTH assays detect only the biologically active 1–84 fragment. Regulation of PTH secretion depends on stimulation of the extracellular calcium-sensing receptor, making serum calcium the primary regulator of hormone release.
Physiology of Parathyroid Hormone
Parathyroid hormone secretion is stimulated when serum calcium levels fall below normal. PTH acts on three main target organs: bones, kidneys, and intestines, to restore calcium balance.
In bone, PTH stimulates osteoclast-mediated bone resorption indirectly by activating osteoblasts, leading to the release of calcium into the bloodstream. In the kidneys, PTH increases calcium reabsorption while decreasing phosphate reabsorption, thereby preventing calcium loss in urine and promoting phosphate excretion. In the intestines, PTH indirectly increases calcium absorption by stimulating the production of calcitriol, the active form of vitamin D.
Mechanism of Action
When blood calcium levels decrease, parathyroid hormone is released into circulation. This hormone increases calcium release from bone, reduces calcium loss through urine, and enhances calcium absorption from the intestine through vitamin D activation.
These combined actions result in an increased concentration of calcium in the blood. Once calcium levels return to normal, PTH secretion is reduced through a negative feedback mechanism mediated by the calcium-sensing receptor on parathyroid cells.
Regulation of PTH Secretion
PTH secretion is tightly regulated by serum ionized calcium levels. Low calcium concentrations stimulate PTH release, while high calcium levels suppress secretion through a negative feedback loop.
Magnesium also plays an important role in modulating PTH secretion. Very low magnesium levels can impair PTH release, leading to functional hypoparathyroidism. This regulation ensures precise control of calcium balance under varying physiological conditions.
Indications for Intact PTH Testing
Estimation of intact PTH is indicated in conditions that disturb calcium metabolism. It is routinely used in the evaluation of hypercalcemia and hypocalcemia.
The test is important in diagnosing primary hyperparathyroidism and assessing secondary hyperparathyroidism, particularly in chronic renal failure. It is also useful in the evaluation of bone disorders such as osteoporosis and osteomalacia.
Intact PTH testing helps assess calcium homeostasis in patients with malabsorption syndromes or endocrine disorders. It is used to monitor response to therapy in calcium-related diseases and is essential for follow-up after parathyroid surgery.
Sample Collection and Handling
For intact PTH estimation, blood is collected in an EDTA (lavender-top) tube. Sample collection is ideally performed between 10:00 am and 4:00 pm to minimize diurnal variation.
Plasma should be separated within 24 hours of venepuncture and stored at 4°C. The sample should be analyzed within 72 hours of collection to ensure result accuracy, given the short half-life of the hormone.
Reference Range
The normal reference range for intact PTH is typically between 10 and 65 pg/mL. However, reference values may vary depending on the laboratory, assay kits, and analytical methods used.
Results should always be interpreted in conjunction with serum calcium, phosphorus, vitamin D levels, and clinical findings.
Causes of Low PTH Levels
Low intact PTH levels are most commonly caused by injury to the parathyroid glands during thyroid or neck surgery. This may result in hypoparathyroidism and subsequent hypocalcemia.
Autoimmune destruction of the parathyroid glands is another cause and may be associated with conditions such as Addison’s disease and pernicious anemia. Severe hypomagnesemia can also lead to reversible suppression of PTH secretion.
Causes of High PTH Levels
Elevated intact PTH levels are seen in chronic kidney failure, where impaired phosphate excretion and reduced vitamin D activation stimulate secondary hyperparathyroidism.
Hypocalcemia is a strong stimulus for increased PTH secretion. Other causes include parathyroid hyperplasia involving two or more glands, parathyroid adenoma, or parathyroid carcinoma. Vitamin D deficiency due to inadequate sunlight exposure, malnutrition, liver failure, certain medications, or lymphoma also leads to increased PTH levels.
Clinical Utility
Intact PTH measurement is critical for evaluating bone health and diagnosing metabolic bone diseases. It guides clinical management of calcium and phosphate disorders and helps differentiate between various causes of hypercalcemia and hypocalcemia.
The test plays an important role in pre-operative and post-operative assessment of patients undergoing parathyroid surgery and is essential for long-term monitoring of calcium-related disorders.
