ABSTRACT
Parathyroid hormone (PTH) is essential for maintaining calcium homeostasis.1-8 It accomplishes this by regulating calcium mobilization from the skeleton, controlling calcium excretion in the kidneys, and stimulating the kidneys to activate vitamin D. Hyperparathyroidism is a consequence of the excess production of PTH by the parathyroid glands. This can be caused by a benign or malignant tumor in the parathyroid gland(s), or stimulation of the parathyroid glands by vitamin D de- ciency, hypocalcemia, or hyperphosphatemia. The consequences of hyperparathyroidism include hypercalciuria, hypercalcemia, hypophosphatemia, osteopenia/osteoporosis, osteomalacia, and kidney stones.1-7 The major causes of hyperparathyroidism are a benign adenoma in a parathyroid gland causing primary hyperparathyroidism, and vitamin D deciency and chronic kidney disease (CKD) causing secondary hyperparathyroidism.1-5
The Chief cells in the parathyroid glands produce PTH. The calcium sensor (calcium receptor, CaR) in the plasma membrane of the Chief cells is constantly monitoring blood ionized calcium levels.4-6 In response to a decrease in serum ionized calcium, there is an immediate increase in the receptor activity leading to signal transduction resulting in the stimulation of nuclear expression of the PTH mRNA, which increases the transcription and translation for PTH.2,6 PTH is transcribed into a 115 amino acid peptide often called the prepro form.2,6 It undergoes posttranslational modication to the 84 amino acid PTH and is then incorporated into secretionary granules that release PTH into the circulation. The first 34 amino acids in the N-terminal region of PTH are responsible for most if not all of the calcium regulating properties of PTH.2,6 PTH interacts with its receptor PTH receptor 1 (PTHR-1) in the kidneys, which stimulates proximal and distal tubular reabsorption of calcium from the ultraltrate and decreases tubular reabsorption of phosphorus (Figure 17.1). PTH interacts with its receptor on the osteoblasts to increase the expression of RANKL (receptor activator of NFκB ligand).8 RANKL, which is on the plasma membrane of the osteoblast, interacts with its receptor RANK present on the monocytic precursor of the osteoclast and stimulates it to become a mature osteoclast to mobilize calcium from the skeleton (Figure 17.2).
