The parathyroid glands are small endocrine glands in the neck of humans and other tetrapods
that produce parathyroid hormone.
Humans usually have four parathyroid glands, variably located on the back of the thyroid
gland, although considerable variation exists.
Parathyroid hormone and calcitonin have key roles in regulating the amount of calcium
in the blood and within the bones.
The parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage
to the thyroid glands.
The parathyroid glands are derived from the epithelial lining of the third and fourth
branchial pouches, with the superior glands arising from the fourth pouch, and the inferior
glands arising form 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, characterised by alterations in the blood
calcium levels and bone metabolism, are states of surplus or insufficient 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 weight about 30mg in men and 35mg in women.
These glands are not visible or able to be felt during examination of the neck.
Blood supply The blood supply, drainage, and lymphatic
drainage of the parathyroid glands correspond to the thyroid overlying gland.
The superior parathyroid glands receive their blood from the inferior thyroid arteries.
The inferior parathyroid glands receive a variable blood supply, from either the ascending
branch of the inferior thyroid arteries or the thyroid ima artery.
The inferior thyroid artery arises from the subclavian arteries.
Each parathyroid vein drains into the superior and, middle and inferior thyroid veins.
The superior and middle thyroid veins drain into the 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 but 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 synthesise 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 early human embryonic life, a series of
six branchial pouches form that given rise to the human 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 sixth is the furthest 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 life.
The pair of glands which is ultimately inferior develops from the third pouch, whereas the
pair of glands which is ultimately superior develops from the fourth pouch.
During embryological development, the third pouch migrates downwards, dragging the inferior
glands with it.
The superior pair are not dragged downwards by the fourth pouch to the same degree.
The glands are named after their final, not embryological, positions.
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 stimulating osteoclasts to break down bone and release
calcium.
PTH also 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.
Clinical significance
Parathyroid disease is conventionally divided into states where the parathyroid is overactive,
and states where the parathyroid is under- or hypoactive.
Both states are characterised by their symptoms, which relate to the excess or deficiency of
parathyroid hormone in the blood.
Hyperparathyroidism
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.
Renal disease may also 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 also known as secondary hyperparathyroidism.
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, although it may also be associated with rarer genetic syndromes such as DiGeorge
syndrome or an autosomal dominant syndrome.
Hypoparathyroidism will also 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, as although the parathyroid glands are fully
functional, 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 but 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 The parathyroid glands were first discovered
in the Indian Rhinoceros by Richard Owen in 1852.
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".
The glands were first discovered in humans by Ivar Viktor Sandström, a Swedish medical
student, in 1880 at Uppsala University.
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.
Physiologist Eugene Gley first documented the putative function of the glands in 1891,
noting the connection between their removal and the development of muscular tetani.
William G. MacCallum in 1908, investigating tumours of the parathyroid, proposed their
role in calcium metabolism.
He noted that "Tetany occurs spontaneously in many forms and may also be produced by
the destruction of the parathyroid glands".
The first successful removal of the parathyroid may have been carried out in 1928 by medical
doctor Isaac Y Olch, whose intern had noticed elevated calcium levels in an elderly patient
with muscle weakness.
Prior to this surgery, patients with removed parathyroid glands typically died from muscular
tetani.
Parathyroid hormone was isolated in 1923 by Adolph M. Hanson and 1925 by James B. Collip.
Studies of parathyroid hormone levels by Roger Guillemin, Andrew Schally and Rosalyn Sussman
Yalow led to the development of immunoassays capable of measuring body substances and a
Nobel Prize in 1977.
In other animals Parathyroid glands are found in all adult
tetrapods, although they vary in their number and position.
Mammals typically have four parathyroid glands, while other types of animals typically have
six.
The removal of parathyroid glands in animals produces a condition resembling acute poisoning
with irregular muscle contractions.
Fish do not possess parathyroid glands, however 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.
Additional images
See also This article uses anatomical terminology;
for an overview, see anatomical terminology.
Thyroid gland Head and neck anatomy
Notes
References
External links Endocrine Web at endocrineweb.com
The origin of the parathyroid gland at pnas.org Parathyroid+gland at eMedicine Dictionary
Virtual Slidebox at Univ.
Iowa Slide 149