Figure 59-1. Normally, there are four parathyroid glands, situated in two pairs with one above the other on the posterior aspect of the thyroid gland. Rarely, the parathyroids may be found inside the thyroid gland itself. In about 10% of individuals, the number exceeds four; on occasion, there are fewer than four glands. The inferior pair of parathyroids, which arise in the branchial arch that also gives rise to the thymus, may descend into the mediastinum.
Synthesis and main functions of parathyroid hormone. *Figures in parentheses indicate number of amino acids in these peptide chains.
Grossly, each parathyroid gland is an encapsulated ovoid structure with a distinctive yellowish-brown color. Its maximal diameter is 5 mm and its weight is 35–40 mg.
Microscopically, the normal parathyroid contains three types of cells: chief cells, water-clear cells, and oxyphil cells. All three are believed to produce hormone, and their relative numbers are of little significance. Variable amounts of adipose tissue are interspersed between parenchymal cells; the amount of adipose tissue increases with age.
The parathyroid glands secrete parathyroid hormone (PTH), an 84-amino-acid polypeptide that is synthesized on the parathyroid cell ribosome as a 115-amino-acid precursor, pre-proPTH. PTH is split off from pre-proPTH in the Golgi zone and secreted directly into the blood. The intact PTH molecule is active. In the blood and peripheral tissues, PTH undergoes final cleavage into amino terminal and carboxyl terminal fragments. The amino terminal fragment contains the active part of the molecule and has a very short half-life. The carboxyl terminal fragment is inactive and has a long half-life. It is removed from plasma exclusively by renal excretion. Serum assays for PTH using radioimmunoassay chiefly measure the inactive carboxyl terminal fragment. In renal failure, elevation of immunoreactive PTH occurs because of decreased clearance of the carboxyl terminal fragment. Newer assays are now available that measure the intact PTH molecule, as well as the amino terminal and carboxyl terminal fragments. Intact PTH molecule assay and amino terminal fragment assay have the most accurate correlation with the rate of PTH secretion by the glands.
PTH regulates the concentration of ionic calcium in plasma. Its main target cells are the renal tubular epithelial cells and bone osteoclasts. In the kidney, PTH increases reabsorption of calcium in the distal tubules and decreases reabsorption of phosphate in the proximal tubule. It also stimulates activation of vitamin D, which in turn increases intestinal absorption of calcium. PTH increases bone resorption (releasing calcium and phosphate) by stimulating osteoclastic activity. This function of PTH requires the synergistic action of active vitamin D. PTH also increases collagenase activity in bone, causing breakdown of the bony matrix.
The overall effect of PTH is an increase in total and ionized plasma calcium and a decrease in plasma inorganic phosphate.