Parathyroid gland
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 a 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.Histology
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
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.Parathyroid hormone 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 to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation 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 of Phosphate is increased.
Disorders
Hyperparathyroidism
Primary
Hyperparathyroidism is the state in which there is excess parathyroid hormone circulating. This may cause bone pain and tenderness, due to increased bone resorption. Due to 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 single gland, and rarely MEN syndrome. This is known as primary hyperparathyroidism, which is generally managed by surgical removal of the abnormal parathyroid gland.Secondary
Renal disease may lead to hyperparathyroidism. When too much calcium is lost, there is a compensation by the parathyroid, and parathyroid hormone is released. The glands hypertrophy to synthesise more parathyroid hormone. This is known as secondary hyperparathyroidism.Tertiary
If this situation exists for a prolonged period of time, the parathyroid tissue may become unresponsive to the blood calcium levels, and begin to autonomously release parathyroid hormone. This is known as tertiary hyperparathyroidism.Hypoparathyroidism
The state of decreased parathyroid activity is known as hypoparathyroidism. This is most commonly associated with damage to the glands or their blood supply during thyroid surgery — it may be associated with rarer genetic syndromes such as DiGeorge syndrome, which is inherited as an autosomal dominant syndrome. Hypoparathyroidism will occur after surgical removal of the parathyroid glands.Occasionally, an individual's tissues are resistant to the effects of parathyroid hormone. This is known as pseudohypoparathyroidism. In this case the parathyroid glands are fully functional, and the hormone itself is not able to function, resulting in a decrease in blood calcium levels. Pseudohypoparathyroidism is often associated with the genetic condition Albright's hereditary osteodystrophy. Pseudopseudohypoparathyroidism, one of the longest words in the English language, is used to describe an individual with Albright's hereditary osteodystrophy; with normal parathyroid hormone and serum calcium levels.
Hypoparathyroidism may present with symptoms associated with decreased calcium, and is generally treated with Vitamin D analogues.
History
- In 1852, Richard Owen discovered the parathyroid glands in the Indian Rhinoceros. In his description of the neck anatomy, Owen referred to the glands as "a small compact yellow glandular body attached to the thyroid at the point where the veins emerged".
- In 1880, Ivar Viktor Sandström, a Swedish medical student, discovered the parathyroid glands in humans as well as other mammals. Unaware of Owen's description, he described the glands in his monograph "On a New Gland in Man and Fellow Animals" as the "glandulae parathyroidae", noting its existence in dogs, cats, rabbits, oxen, horses and humans. For several years, Sandström's description received little attention.
- In 1891, physiologist Eugène Gley first documented the function of the parathyroid glands. He also noted the connection between their removal and the development of tetany.
- In 1908, William G. MacCallum, investigating tumors of the parathyroid, proposed their role in calcium metabolism. He noted that "Tetany occurs spontaneously in many forms and may be produced by the destruction of the parathyroid glands".
- In 1928, the first successful removal of the parathyroid was reported by Isaac Y Olch, whose intern had noticed elevated calcium levels in an elderly patient with muscle weakness.
- In 1923, parathyroid hormone was isolated by Adolph M. Hanson, and in 1925 by James B. Collip.
- In 1977, Roger Guillemin, Andrew Schally and Rosalyn Sussman Yalow won the Nobel Prize for the development of immunoassays capable of measuring various substances in the serum, including parathyroid hormone.
Other animals
Fish do not possess parathyroid glands; several species have been found to express parathyroid hormone. Developmental genes and calcium-sensing receptors in fish gills are similar to those within the parathyroid glands of birds and mammals. It has been suggested that the tetrapod glands may have been evolutionarily derived from these fish gills.