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This chapter presents a general overview of the key hormones involved in the regulation of calcium, phosphate, and bone mineral metabolism. These include parathyroid hormone, vitamin D—principally the 1,25-(OH)2 vitamin D metabolite (1,25-dihydroxycholecalciferol)—calcitonin, and fibroblast growth factor(FGF)-23. The cycle of bone remodeling is described as a basis for understanding normal maintenance of skeletal integrity in adults and of mineral homeostasis. The symptoms and signs caused by excess or deficiency of the calciotropic hormones are presented along with the natural histories of primary hyperparathyroidism, familial (benign) hypocalciuric hypercalcemia, hypercalcemia of malignancy, different forms of hypoparathyroidism, and medullary carcinoma of the thyroid. Two of the most commonly encountered causes of low bone mass—osteoporosis and osteomalacia—are reviewed, along with discussions regarding their pathogenesis.

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Parathyroid Glands

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Anatomy

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Normal parathyroid glands each weigh 30–40 mg and are gray-tan to yellow-gray. Each individual typically has four glands, so that the average total parathyroid tissue mass in the adult is 120–160 mg.

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The superior pair of parathyroid glands arise from the fourth branchial pouches in the embryo. These glands are located near the point of intersection of the middle thyroid artery and the recurrent laryngeal nerve. The superior parathyroid glands may be attached to the thyroid capsule posteriorly or, rarely, embedded in the thyroid gland itself. Alternative locations include the tracheoesophageal groove and the retroesophageal space. The blood supply to the superior parathyroid glands is from the inferior thyroid artery or, less commonly, the superior thyroid artery.

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The inferior parathyroid glands develop from the third branchial pouch, as does the thymus gland. These glands typically lie at or near the lower pole of the thyroid gland lateral to the trachea. The inferior glands receive their blood supply from the inferior thyroid arteries. The location of the inferior parathyroid glands is variable. When there are ectopic glands, they are typically found in association with thymic remnants. A common site for ectopic glands is the anterior mediastinum. Less common ectopic locations are the carotid sheath, pericardium, and pharyngeal submucosa. About 10% of people have additional (supernumerary) parathyroid glands.

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Histology

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The parathyroid gland is composed of three different cell types: chief cells, clear cells, and oxyphil cells. Chief cells are small in diameter (4–8 μm) with central nuclei and are thought to be responsible for the synthesis and secretion of parathyroid hormone(PTH). In their active state, they have a prominent endoplasmic reticulum and dense Golgi regions where PTH is synthesized and packaged for secretion. Clear cells are probably chief cells with an increased glycogen content. Oxyphil cells appear in the parathyroid glands after puberty. They are larger than chief cells (6–10 μm), and their number increases with age. It is not clear whether these cells secrete PTH and whether they are derived from chief cells.

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