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Parathyroid glands

The parathyroid glands (Latin: glandula parathyreoidea inferior, glandula parathyreoidea superior) are multiple small endocrine glands responsible for parathyroid hormone production (PTH) as a response to the blood calcium levels. The parathyroid glands are essential in regulating calcium homeostasis. 

Parathyroid gland anatomy

Humans have four (some people can have up to 6) parathyroid glands that are small, flattened, oval-shaped. The parathyroid glands are located on the posterior surfaces of the right and left lobes of the thyroid glands. The parathyroid glands are yellowish-brown, the length is 6 mm, the width is 4 mm, the thickness is 2 mm, and the weight is 30-35 g. There are two parathyroid glands on each side. The ones that are positioned higher are called the superior parathyroid glands, but the lower ones are called the inferior parathyroid glands:

  • Superior parathyroid glands - their location is constant. The superior parathyroid glands can be found at the middle of each thyroid lobe's posterior border, at the level of the inferior border of the cricoid cartilage. They are around 1 cm superior to the entry of the inferior thyroid artery into the thyroid gland. The superior parathyroid glands are derived from the fourth pharyngeal pouch. 
  • Inferior parathyroid glands - in contrast to the superior parathyroid glands, the inferior can have various locations, but usually, they are located near the inferior poles of the thyroid glands. In some cases, the inferior parathyroid glands can be situated as far down as the superior mediastinum. The inferior parathyroid glands are derived from the third pharyngeal pouch. 

Parathyroid gland microanatomy

The parathyroid glands have two cell types within them: chief cells and oxyphil cells. These cells are densely packed. 

Chief cells 

Chief cells are also known as the parathyroid principal cells or just parathyroid cells. Chief cells take up the most significant part of the cells in the parathyroid gland. Despite the considerable number of them in the parathyroid glands, they are smaller than the other cell type. The chief cells have a polygonal shape with a round nucleus. Chief cells are mostly inactive under the condition that the body has a normal calcium level. Dormant chief cells have a small number of secretory granules, while active cells have more. If the body has a low calcium level, the chief cells become active. The chief cells have a calcium-sensing receptor that helps them. These cells are responsible for secreting PTH. The cells contain Golgi apparatus and endoplasmic reticulum that are needed for the synthesis and secretion of PTH. 

Oxyphil cells

Within the parathyroid gland, the oxyphil cells are less in number but bigger in size compared to the chief cells. The function of the oxyphil cells is unknown. The oxyphil cells appear only during puberty and increase in number with age. Because of their late appearance, it is thought that the oxyphil cells are derived from the chief cells. The oxyphil cells have many mitochondria, while the endoplasmic reticulum, Golgi apparatus, and secretory granules are poorly developed. 

Parathyroid gland functions

The main function of the parathyroid glands is to regulate calcium and phosphate levels within a very narrow range in the blood hormonally. This is important so that the nervous and muscular systems can work properly. The parathyroid glands do this by producing the parathyroid hormone (PTH).

Parathyroid hormone 

Parathyroid hormone is secreted by the chief cells. PTH regulates the serum calcium and phosphate levels by affecting bones, kidneys, and the intestine. 

PTH secretion is stimulated by:

  • decreased serum calcium
  • mild decrease in serum magnesium
  • increased serum phosphate
  • adrenaline
  • histamine

PTH secretion is inhibited by:

  • increased serum calcium
  • a significant decrease in serum magnesium
  • calcitriol
  • increase in serum phosphate.

The PTH acts on cells of the bones, causing them to release calcium into the bloodstream, thus also regulating the amount of calcium in the bones and therefore affecting the strength and density of the bones. PTH is secreted as a response to low blood serum calcium. PTH stimulates osteoclast activity to release more ionic calcium from the bones into the bloodstream to increase serum calcium levels. The bones work as the reservoir of calcium to maintain normal serum calcium levels. PTH indirectly affects osteoclasts by binding to osteoblasts. Another way that the PTH can raise calcium levels is by acting upon the epithelial cells lining the intestinal tract to increase calcium absorption from the diet.

PTH also affects serum phosphate levels. PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, resulting in increased excretion through the urine. 

PTH stimulates the uptake of phosphate from the intestine and bones into the bloodstream. The absorption of calcium and phosphate from the intestines is mediated by an increase in activated vitamin D. Calcium absorption is more dependant on vitamin D than phosphate absorption. PTH also upregulates the enzyme responsible for converting vitamin D to its active form.

Vasculature and innervation of the parathyroid glands

Arterial supply

The arterial supply to the parathyroid glands is similar to the thyroid gland. The parathyroid glands receive their blood supply from branches of the inferior thyroid arteries, which arise from the subclavian arteries. They can also be supplied by anastomoses between the superior and inferior thyroid arteries, the thyroid ima artery, and other collateral circulation vessels. 

Venous drainage

The parathyroid glands are drained through the superior, middle and inferior thyroid veins. The superior and middle thyroid veins end in the internal jugular vein, while the inferior thyroid vein drains into the brachiocephalic vein. All three thyroid veins form a thyroid venous plexus around the thyroid gland. 

Lymphatic drainage

The lymph from the parathyroid glands is drained into the paratracheal and deep cervical lymph nodes. 

Innervation

The endocrine secretion of the parathyroid glands is regulated hormonally, while their blood vessels receive rich innervation from the sympathetic nervous system via branches arising from the thyroid branches of the cervical ganglia of the sympathetic chain. These nerves are vasomotor, not secretomotor. 

Most common parathyroid glands disorders

The parathyroid gland diseases are divided into two groups based on the activity of the parathyroid glands. If the parathyroid glands are overactive, it is known as hyperparathyroidism. On the other hand, if the parathyroid glands are underactive, it is known as hypoparathyroidism

Hyperparathyroidism

Hyperparathyroidism means an increase in PTH levels in the blood. Hyperparathyroidism can be divided into primary, secondary, and tertiary hyperparathyroidism. 

Primary hyperparathyroidism is caused by a tumor in the parathyroid gland. It can be parathyroid adenoma, parathyroid hyperplasia, or parathyroid carcinoma. 

In the case of primary hyperparathyroidism, the symptoms resemble hypercalcemia symptoms:

  • kidney stones, nephrocalcinosis
  • constipation, indigestion
  • nausea, vomiting
  • osteoporosis, osteomalacia
  • lethargy, fatigue
  • depression
  • memory loss
  • psychosis, delirium

Surgery to remove the parathyroid gland usually is the first step of treatment. Sometimes medication can be needed. 

Secondary hyperparathyroidism usually occurs as a response to long-term hypocalcemia. The most common cause of hypocalcemia is chronic kidney failure. In rarer cases, the reason may be malabsorption. Most of the symptoms in the case of secondary hyperparathyroidism are coming from the underlying disease. People can also experience bone and joint pain, limb deformities. The treatment usually starts by treating the underlying cause. 

Tertiary hyperparathyroidism occurs after prolonged secondary hyperparathyroidism when the parathyroid glands do not respond to the serum calcium levels. Symptoms usually are the same as in the primary hyperparathyroidism and hypercalcemia. Treatment is based on the underlying cause. 

Hypoparathyroidism 

Hyperparathyroidism occurs when the parathyroid glands are not working properly, secreting decreased PTH levels and resulting in low serum calcium levels

Hyperparathyroidism can be caused by removing the parathyroid glands, autoimmune activity, magnesium deficiency, hemochromatosis.

Symptoms of hypoparathyroidism are:

  • paresthesia
  • fatigue, headaches
  • bone pains
  • insomnia
  • abdominal cramps
  • Chvostek's sign - twitching of the facial muscles by stimulating the facial nerve
  • Trousseau's sign - hyperreflexia and tetany after obstructing the blood flow to the arm using a blood pressure cuff.

Treatment needs to be started with intravenous calcium as severe hypocalcemia can be life-threatening. Vitamin D is prescribed as a long-term treatment. 

Summary on the parathyroid glands 

Where are the parathyroid glands located?

The parathyroid glands are located on the posterior surfaces of the right and left lobes of the thyroid glands. The parathyroid glands are yellowish-brown, the length is 6 mm, the width is 4 mm, the thickness is 2 mm, and the weight is 30-35 g. There are two parathyroid glands on each side. 

How many parathyroid glands we have?

Usually, we have four parathyroid glands, but a small number of people may have up to six parathyroid glands. 

What are the functions of the parathyroid gland?

The main function of the parathyroid glands is to regulate calcium and phosphate levels within a very narrow range in the blood hormonally. This is important so that the nervous and muscular systems can work properly. The parathyroid glands do this by producing the parathyroid hormone (PTH).

What are the signs and symptoms of parathyroid disease?

In the case of hyperthyroidism, the symptoms resemble hypercalcemia and are kidney stones, nephrocalcinosis, constipation, indigestion, nausea, vomiting, in case of tumor people may see a lump on the neck, osteoporosis, osteomalacia, lethargy, fatigue, depression, memory loss, psychosis, delirium, as well symptoms of the underlying disease.

Symptoms of hypoparathyroidism are paresthesia, fatigue, headaches, bone pain, insomnia, abdominal cramps, Chvostek's sign - twitching of the facial muscles by stimulating the facial nerve, Trousseau's sign - hyperreflexia and tetany after obstructing the blood flow to the arm using a blood pressure cuff.

What are the three types of hyperparathyroidism?

Primary hyperparathyroidism is caused by a tumor in the parathyroid gland. Secondary hyperparathyroidism usually occurs as a response to long-term hypocalcemia. Tertiary hyperparathyroidism occurs after prolonged secondary hyperparathyroidism when the parathyroid glands do not respond to the serum calcium levels. 

What happens if the parathyroid hormone is high?

An increase in PTH can lead to hyperparathyroidism. 

What happens if the parathyroid disease goes untreated?

Untreated hypercalcemia can lead to osteoporosis, kidney stones, depression, psychosis, memory loss, osteomalacia.

Untreated hypocalcemia can lead to a life-threatening situation with paresthesia, cramps, and tetany.

What tests are done to diagnose parathyroid disease?

Calcium level, PTH level, urine calcium, vitamin D, phosphate level, magnesium level. Additionally to blood tests, the doctor could recommend an ultrasound, MRI or CT, abdominal X-ray, bone densitometry. 

Should you take vitamin D if you have hyperparathyroidism?

Every case needs to be examined carefully. Vitamin D can be given to people with asymptomatic hyperparathyroidism, but serum calcium and urine calcium must be monitored.