Bastepe M., Jüppner H., Thakker RV.
This chapter discusses the disorders related to parathyroid hormone (PTH). Extracellular calcium ion concentration is tightly regulated through the actions of PTH on the kidneys and bone. The intact peptide is secreted from the parathyroid glands at a rate that is appropriate to and dependent on the prevailing extracellular calcium ion concentration. Hypercalcemic or hypocalacemic disorders can be classified according to whether they occur from an excess or deficiency of PTH, a defect in the PTH receptor [that is, the PTH/PTH-related peptide (PTHrP) receptor], or insensitivity to PTH caused by defects downstream of the PTH/PTHrP receptor. Recent advances in understanding the biological importance of the key proteins involved in the regulation of PTH secretion and the responsiveness to PTH in target tissues have led to the identification of molecular defects in a variety of disorders and thus enabled the characterization of some of the mechanisms involved in the regulation of parathyroid gland development, parathyroid cell proliferation, PTH secretion, and PTH-mediated actions in target tissues. For example, mutations in the calcium-sensing receptor gene have been reported in patients with familial benign (hypocalciuric) hypocalcaemia (FBH) or familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism, and autosomal-dominant hypocalcemia. © 2003 Elsevier Inc. All rights reserved.