Hypercalcemia, Hypocalcemia, and the Parathyroid Glands

Calcium is a vital chemical in our bodies and has many functions. It's needed for muscle contraction (including the contraction of the heart muscle), nerve and brain function, bone formation, blood clotting, and many other jobs. Although an adequate amount of calcium in the blood is essential for our health, too much can be dangerous.

The parathyroid glands are small structures that are located in the neck. Their job is to make parathyroid hormone, also known as PTH or parathormone. PTH stimulates body processes that increase the amount of calcium in the blood.

If too much PTH is made, hypercalcemia develops. Hypercalcemia is a disorder in which the blood contains excess calcium. On the other hand, if too little PTH is made, hypocalcemia develops. In hypocalcemia, the blood doesn't contain enough calcium. Either condition may range in severity from a minor problem to a serious disease. Luckily, treatments are available for both disorders.

The four parathyroid glands are usually found behind the thyroid gland, which is also known as the thyroid. Occasionally, one or more of the glands may be found inside the thyroid gland, in the neck above the thyroid, or even in the chest behind the sternum or breastbone.

Although the parathyroid glands are located next to the thyroid, they are structurally and functionally distinct from it. It wasn't until 1850 that the glands were considered to be separate entities, however. Sir Richard Owen is credited with their discovery.

Owen was an anatomist and paleontologist. He noticed the presence of the parathyroid glands when he dissected a dead Indian rhinoceros from the London Zoo, although at this point they had no name and their function was unknown. Richard Owen is also famous for his creation of the name "dinosaur" from the Greek words for "terrible lizard" and for his criticism of Charles Darwin's theory of evolution by natural selection.

A molecule of parathyroid hormone is a protein made of 84 amino acids. The hormone does its job by affecting the bones, the intestine, and the kidneys. In a healthy body, the level of PTH is adjusted to keep the calcium level in the blood constant. There are factors that can hinder this control of the calcium level, however.

• Parathyroid hormone stimulates the activity of osteoclasts, which are cells in bone that break the bone down. The process releases calcium into the bloodstream. (Other cells called osteoblasts build bone.)

• PTH increases the absorption of calcium from the digested food in the small intestine by promoting the formation of the active form of vitamin D. The vitamin helps calcium to pass from the small intestine into the bloodstream.
• PTH stimulates calcium reabsorption in the kidneys so that the calcium isn't eliminated from the body in the urine. In the kidneys, calcium (which exists as calcium ions in the body) is filtered out of the blood into the kidney tubules. Some is then reabsorbed further along in the kidney tubules, passing from the tubules into the surrounding blood vessels. Any calcium that stays in the tubules is excreted in the urine.

Parathyroid hormone also decreases the reabsorption of phosphorus in the kidney, reducing its level in the blood and increasing the amount in urine. Phosphorus travels through the blood in the form of phosphate.

The most common cause of hypercalcemia is primary hyperparathyroidism, a condition arising from a problem in a parathyroid gland. The problem is usually a tumor, or adenoma. The tumor is generally benign, which means that it doesn't spread through the body.

When a parathyroid gland enlarges, the additional cells produce extra PTH. This results in an elevated calcium level in the blood. The bones may weaken as PTH stimulates them to release calcium. Extra calcium may travel through the kidneys, producing kidney stones. Fortunately, a tumor on a parathyroid gland can generally be removed by surgery.

A benign tumor (or tumors) is usually responsible for hypercalcemia, but there are many other possible causes.

• Some prescribed medications can cause the condition.
• Taking large amounts of calcium or vitamin D supplements for a long time may also increase the calcium level in the blood.
• Dehydration can produce a temporary increase in the concentration of calcium in the bloodstream.
• Lying immobilized in bed for a long period of time may cause hypercalcemia.
• Kidney or adrenal gland problems can produce hypercalcemia, and so can problems with other hormones in the body besides PTH.
• Some types of inflammation or cancer can cause the disorder as well.

In a rare inherited condition known as familial hypocalciuric hypercalcemia, the gene that codes for a calcium-sensing receptor doesn't work properly. This receptor is present in the parathyroid glands as well as in other parts of the body. Without a properly functioning receptor, the parathyroid gland isn't "told" that the blood contains calcium, so it continues to make PTH. This raises the level of calcium in the blood.

The following symptoms may indicate the presence of hypercalcemia, although they can also indicate other health problems. Some people who have the disorder have no symptoms, especially when the condition is mild.

• Bone problems: pain, curvature of bones, fractures
• Muscle problems: weakness, twitches
• Gastrointestinal tract problems: pain, nausea, vomiting, loss of appetite, constipation
• Kidney problems: back pain, thirst, frequent urination
• Nervous system problems: memory loss, confusion, depression, fatigue

Hypoparathyroidism is a rare disorder in which the parathyroid glands are inactive or underactive. Two possible causes of the disorder are the removal of the parathyroid glands during thyroid gland surgery and injury to the glands during neck surgery. An autoimmune disease that attacks the glands may also cause hypoparathyroidism.

Low magnesium levels may prevent enough PTH from being made. In addition, there are inherited conditions that prevent the production of PTH. One of these conditions is DiGeorge syndrome. A person with this condition may be born with no parathyroid glands.

When parathyroid glands are missing or damaged, either no PTH is produced or the amount that is made is insufficient. The hormone problem causes the calcium level in the blood to fall. It also causes the level of phosphorus in the blood to rise, since phosphorus reabsorption in the kidney is no longer being inhibited.

Occasionally the parathyroid glands are working correctly but the bones or kidneys fail to respond to PTH, resulting in a condition called pseudohypoparathyroidism. This may lead to hypocalcemia.

As is the case for hypercalcemia, having one or more of the following symptoms could indicate the presence of another health problem instead of hypocalcemia. If someone has unexplained symptoms that worry them they should visit a doctor.

• tingling in the lips, fingers or toes
• muscle aches or cramps
• muscle twitches
• weakness and fatigue
• dry skin
• brittle nails
• hair loss
• headaches
• anxiety
• depression
• memory loss

Complications of hypocalcemia include heart, kidney or teeth problems, the development of cataracts, or the formation of calcium deposits in the brain.

Calcium and vitamin D supplements in appropriate doses are usually prescribed for hypocalcemia caused by hypoparathyroidism. Doctors may also prescribe other medications to raise the blood calcium level. In addition, a diet that is high in calcium and low in phosphorus may be recommended.

A patient may have to take supplements and follow a special diet for the rest of his or her life, but this routine should remove symptoms and prevent complications of the disease. As in hypercalcemia, the problems created by hypocalcemia and the patient's quality of life can very often be improved by following appropriate medical treatment.

Hypercalcemia Information from the National Institutes of Health

Facts about hypercalcemia from the Mayo Clinic

Hypocalcemia Information from the Merck Manual

Parathyroid disorders from the U.S. National Library of Medicine

Hypoparathyroidism and hyperparathyroidism from the National Health Service