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.
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
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.
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.
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.