PTH Intact

Parathyroid hormone (PTH) is synthesized by the chief cells of the parathyroid glands and stored into dense neuroendocrine-type secretory granules, awaiting secretion. Intact PTH is an 84 amino acid polypeptide with a molecular mass of approximately 9.43 kilodaltons. After secretion PTH undergoes rapid proteolysis to generate various circulating C-terminal fragments. Some of these fragments re-enter the bloodstream and are cleared primarily by glomerular filtration, an important route for PTH clearance.

PTH plays a crucial role in maintaining calcium homeostasis and its measurement is an important aid in the diagnosis of calcium related disorders. In healthy individuals, PTH secretion responds to small alterations in plasma ionized calcium concentration within seconds. Abnormally low ionized calcium concentrations trigger PTH secretion, whereas rising levels of extracellular calcium reduce PTH secretion through a negative feedback mechanism.

PTH regulates calcium levels by concerted effect on three principal organs: bone, intestinal mucosa and kidney. The effect of PTH on intestinal calcium is indirect, resulting from renal production of the intestinally active vitamin D metabolite, 1,25-dihydroxyvitamin D. In the kidney, PTH stimulates calcium reabsorption and inhibition of phosphate reabsorption from the renal tubules. Eventually PTH promotes osteoclastic bone resorption and release of calcium and phosphate from bone.

In patients with disorders of calcium metabolism, quantitative determination of circulating PTH may assist in the differential diagnosis of hypercalcemia and hypocalcemia. In hypercalcemia due to primary hyperparathyroidism or ectopic PTH secretion (pseudo hyperparathyroidism), most patients have increased PTH levels. By contrast in hypercalcemia due to malignancy or other causes, the concentration of PTH in the circulation is typically low, either below or towards the low end of the reference range for apparently healthy individuals.

Secondary hyperparathyroidism is a compensatory hyperfunctioning of the parathyroid glands caused by hypocalcemia or peripheral resistance to PTH. It is typically caused by renal failure and leads to elevated PTH levels. Chronic overproduction of PTH in renal failure contributes to the spectrum of bone disease, which is also termed renal osteodystrophy. The National Kidney Foundation (NKF) has published clinical practice guidelines addressing bone metabolism for the management of chronic kidney disease. It recommends that serum levels of calcium, phosphorus and PTH be measured periodically in all patients with chronic kidney disease. Since this condition is a complex and multifactorial disease, PTH results should be interpreted in light of all the information available to the clinician.

Hypoparathyroidism is an uncommon congenital or acquired condition in which PTH secretion is deficient or absent. In most cases, hypoparathyroidism follows parathyroidectomy or thyroidectomy.