parathyroid glands

parathyroid glands, four small endocrine bodies, located behind the thyroid gland, that govern calcium and phosphorus metabolism. These four masses of tissue (each about the size of a pea) are difficult to distinguish from the thyroid and are often embedded in it. Consequently, before their significance was known they were sometimes accidently removed during thyroid surgery, causing a deficiency in parathormone, the parathyroid hormone. Parathormone increases the concentration of calcium ions in the blood, with accompanying bone absorption and increased reabsorption of calcium ions by the kidneys. The hormone's effect on phosphate ion concentration is the opposite, i.e., phosphate ion concentration in the bloodstream decreases as a result of increased phosphate excretion by the kidneys. Excessive secretion of parathormone, e.g., caused by tumor of the parathyroid glands, is a serious disorder, for excessive blood calcium can cause kidney stones and long-term weakening of the bones. Undersecretion of parathormone, which can be caused by congenital and metabolic disorders, results in too little calcium in the bloodstream, and too much phosphorus. The result is tetany, i.e., violent muscle spasms.

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Parathyroid gland

The parathyroid glands are small endocrine glands in the neck, usually located behind the thyroid gland, which produce parathyroid hormone. In rare cases the parathyroid glands are located within the thyroid glands. Most often there are four parathyroid glands, but some people have six or even eight.

Anatomy

The parathyroid glands are four or more small glands located on the posterior surface of the thyroid gland. Histologically they are quite easily recognizable from the thyroid as they have densely packed cells in contrast with the follicle structure of the thyroid. However at surgery they are harder to differentiate from the thyroid or fat.

They distinguish themselves from the thyroid gland histologically as they contain two types of cells:

Name	Staining	Quantity	Size	Function
parathyroid chief cells	darker	many	smaller	manufacture PTH (see below).
oxyphil cells	lighter	few	larger	function unknown.

History

The parathyroid glands were discovered by Ivar Viktor Sandström (1852-1889), a Swedish medical student, in 1880. It was the last major organ to be recognized in humans.

Physiology

The sole function of the parathyroid glands is to maintain the body's calcium level within a very narrow range, so that the nervous and muscular systems can function properly.

When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release hormone into the blood.

Parathyroid hormone (PTH, 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. It increases blood calcium levels by stimulating osteoclasts to break down bone and release calcium. It also increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium uptake by the kidneys.

Role in disease

Hyperparathyroidism and related conditions

The single major disease of parathyroid glands is overactivity of one or more of the parathyroid lobes, which make too much parathyroid hormone causing a potentially serious calcium imbalance. This is called hyperparathyroidism; it leads to hypercalcemia and osteitis fibrosa cystica. Since hyperparathyroidism was first described in 1925, the symptoms have become known as "moans, groans, stones, and bones." The primary treatment for this disease is the surgical removal of the faulty gland.

Modern high frequency ultrasound can see parathyroid masses, even before they cause high calcium. They are called parathyroid incidentalomas. If a patient has elevated calcium, the ultrasound can be used to locate the abnormal glands. The use of ultrasound guided FNA, and parathyroid hormone washings can confirm the abnormal glands. A blood calcium 15-30 minutes after the biopsy can help determine if the disease is caused by a single abnormal gland or multiple glands.

A drop in serum calcium suggests a single source, and no drop suggests multiple glands. This, with a non-localizing Sestamibi scan would point toward a neck exploration, rather than a minimally invasive method aimed a single gland disease.

A Sestamibi scan is often used to determine which parathyroid gland(s) are responsible for overproduction of parathyroid hormone.

Another related condition is called secondary hyperparathyroidism, or secondary HPT - common in patients with chronic kidney disease on dialysis. In secondary HPT, the parathyroid glands make too much parathyroid hormone (PTH), and the kidneys do not produce enough vitamin D, and calcium and phosphorus are out of balance. Even though one may not have any symptoms, treating secondary HPT is important. Cinacalcet (Sensipar) is a medicine that can help treat such dialysis patients and is available by prescription only.

Hypoparathyroidism and related conditions

Hypoparathyroidism
Pseudohypoparathyroidism
Pseudopseudohypoparathyroidism
Disorders of the parathyroid hormone receptor have been associated with Jansen's metaphyseal chondroplasia and Blomstrand's chondroplasia.

Embryology and Evolution

The parathyroid glands originate from the interaction of neural crest mesenchyme and third and fourth branchial pouch endoderm.

Genetically, Eya-1 (transcripitonal co-activator), Six-1 (a homeobox transcription factor), and Gcm-2 (a transcription factor) have been associated with the development of the parathyroid gland, and alterations in these genes alters parathyroid gland development.

The conserved homology of genes and calcium sensing receptors in fish gills with those in the parathryroid glands of birds and mammals is recognized by evolutionary developmental biology as evolution using genes and gene networks in novel ways to generate new structures with some similar functions and novel functions.