Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones. Parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage to the thyroid glands. Parathyroid glands are derived from the epithelial lining of the third and fourth pharyngeal pouches, with the superior glands arising from the fourth pouch and the inferior glands arising from the higher third pouch. The relative position of the inferior and superior glands, which are named according to their final location, changes because of the migration of embryological tissues. Hyperparathyroidism and hypoparathyroidism, characterized by alterations in the blood calcium levels and bone metabolism, are states of either surplus or deficient parathyroid function.
Structure The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of the thyroid. Each gland is a yellowish-brown flat ovoid that resembles a lentil seed, usually about 6 mm long and 3 to 4 mm wide, and 1 to 2 mm anteroposteriorly. There are typically four parathyroid glands. The two parathyroid glands on each side which are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Healthy parathyroid glands generally weigh about 30 mg in men and 35 mg in women. These glands are not visible or able to be felt during examination of the neck. Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the internal jugular vein, and the inferior thyroid vein drains into the brachiocephalic vein.
Lymphatic drainage Lymphatic vessels from the parathyroid glands drain into deep cervical lymph nodes and paratracheal lymph nodes.
Variation The parathyroid glands are variable in number: three or more small glands, and can usually be located on the posterior surface of the thyroid gland. Occasionally, some individuals may have six, eight, or even more parathyroid glands. Rarely, the parathyroid glands may be within the thyroid gland itself, the chest, or even the thymus.
Microanatomy The parathyroid glands are named for their proximity to the thyroid—and serve a completely different role than the thyroid gland. The parathyroid glands are quite easily recognizable from the thyroid as they have densely packed cells, in contrast with the follicular structure of the thyroid. Two unique types of cells are present in the parathyroid gland:
Chief cells, which synthesize and release parathyroid hormone. These cells are small, and appear dark when loaded with parathyroid hormone, and clear when the hormone has been secreted, or in their resting state. Oxyphil cells, which are lighter in appearance and increase in number with age, have an unknown function.
Development In the early development of the human embryo, a series of five pharyngeal arches and four pharyngeal pouches form that give rise to the face, neck, and surrounding structures. The pouches are numbered such that the first pouch is the closest to the top of the embryo's head and the fourth is the farthest from it. The parathyroid glands originate from the interaction of the endoderm of the third and fourth pouch and neural crest mesenchyme. The position of the glands reverses during embryological development. The pair of glands which is ultimately inferior develops from the third pouch with the thymus, whereas the pair of glands which is ultimately superior develops from the fourth pouch. During embryological development, the thymus migrates downward, dragging the inferior glands with it. The superior pair are not dragged downward by the fourth pouch to the same degree. The glands are named after their final, not embryological, positions. Since the thymus's ultimate destination is in the mediastinum of the chest, it is occasionally possible to have ectopic parathyroids derived from the third pouch within the chest cavity if they fail to detach in the neck. Parathyroid development is regulated by a number of genes, including those coding for several transcription factors.
Function
The major function of the parathyroid glands is to maintain the body's calcium and phosphate levels within a very narrow range, so that the nervous and muscular systems can function properly. The parathyroid glands do this by secreting parathyroid hormone (PTH). Parathyroid hormone (also known as parathormone) is a small protein that takes part in the control of calcium and phosphate homeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin.
Calcium. PTH increases blood calcium levels by directly stimulating osteoblasts and thereby indirectly stimulating osteoclasts (through RANK/RANKL mechanism) to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation (reabsorption) by the kidneys. Phosphate. PTH is the major regulator of serum phosphate concentrations via actions on the kidney. It is an inhibitor of proximal tubular reabsorption of phosphorus. Through activation of vitamin D the absorption (intestinal) of phosphate is increased.
Disorders
Parathyroid disease is conventionally divided into states where the parathyroid is overactive (hyperparathyroidism), and states where the parathyroid is under- or hypoactive (hypoparathyroidism). Both states are characterised by their symptoms, which relate to the excess or deficiency of parathyroid hormone in the blood.
Hyperparathyroidism
Primary
Hyperparathyroidism is the state in which there is excess parathyroid hormone circulating in the blood. This may cause bone pain and tenderness, due to increased bone resorption. With increased circulating calcium, there may be other symptoms associated with hypercalcemia, most commonly dehydration. Hyperparathyroidism is most commonly caused by a benign proliferation of chief cells in one parathyroid gland, and rarely in MEN syndrome. This is known as primary hyperparathyroidism, which is generally managed by surgical removal of the abnormal parathyroid gland.
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