What are hyperparathyroidism and hypoparathyroidism?

Causes and Symptoms

The precise regulation of calcium is vital to the survival and well-being of all animals. Approximately 99 percent of the calcium in the body is found in bones and teeth. Of the remaining 1 percent, about 0.9 percent is packaged within specialized organelles inside the cell. This leaves only 0.1 percent of the total body calcium in blood. Approximately half of this calcium is either bound to proteins or complexed with phosphate. The other half of blood calcium is free to be utilized by cells. For this reason, it is critical that calcium inside the cell be rigorously maintained at extremely low concentrations. Even a slight change in calcium outside the cell can have dramatic consequences.

The function and regulation of calcium. Calcium plays a vital role in many different areas of the body. For example, the entry of calcium into secretory cells, such as nerve cells, triggers the release of neurotransmitters into the synapse. A fall in blood calcium results in the overexcitability of nerves, which can be felt as a tingling sensation and numbness in the extremities. Similarly, calcium entry into cells is essential for muscle contraction in both heart and skeletal muscle.

Free calcium is thus one of the most tightly regulated substances in the body. The key player in the moment-to-moment regulation of calcium is parathyroid hormone (PTH). PTH is synthesized in the parathyroid glands, a paired gland located in the neck, and released in response to a fall in blood calcium. PTH serves several functions: to increase blood calcium, to decrease blood phosphate, and to stimulate the conversion of vitamin D into its active form, which can then stimulate the uptake of calcium across the digestive tract. Together these actions result in an increase in free calcium, which returns calcium concentrations in the blood to normal.

PTH binds to specific receptors located primarily in bone and kidney tissue. Since most calcium is stored in bone, it serves as a bank for withdrawal of calcium in times of need. Activation of a PTH receptor on osteoclasts, or bone-cutting cells, results in the production of concentrated acids that dissolve calcium from bone, thereby making more free calcium available to the blood supply. PTH also acts on the kidney, where it stimulates calcium uptake from the urine while promoting phosphate elimination. As a result, more calcium is made available to the blood and less phosphate is available to form complexes with the free calcium.

By exerting these effects on its target organs, PTH can restore low calcium concentrations in the blood to normal. Once calcium has returned to a particular set point, PTH secretion is slowed dramatically. If PTH release is not controlled, however, the imbalance in calcium can lead to life-threatening situations. These conditions are termed hyperparathyroidism and hypoparathyroidism.

Hyperparathyroidism. This disorder is defined as the excessive and uncontrolled secretion of PTH. The release of a closely related substance, PTH-related protein, from cancer cells can also cause this condition. Hyperparathyroidism is found in 0.1 percent of the population and is more common in the elderly, who have an incidence rate of approximately 2 percent.

There are two types of hyperparathyroidism: primary and secondary. Primary hyperparathyroidism is caused by disease or damage to the parathyroid glands. For example, cancer of the parathyroid gland can result in the uncontrolled release of PTH and is characterized by an increase in blood calcium. The symptoms associated with primary hyperparathyroidism include
osteoporosis, muscle weakness, nausea, and increased incidence of kidney stones and peptic ulcers. These symptoms can all be linked to the presence of excess calcium, which is a result of the oversecretion of PTH.

Secondary hyperparathyroidism often results when PTH cannot function normally, such as in kidney failure or insensitivity of target tissues to PTH. Secondary hyperparathyroidism is usually characterized by an overall decrease in blood calcium levels, even though there is a marked increase in the amount of PTH being released. Its symptoms may include muscle cramps, seizures, paranoia, depression, and, in severe cases, tetany (the tonic spasm of muscles). These symptoms are a direct result of the decline in available calcium.

Hypoparathyroidism. Less common than hyperparathyroidism, hypoparathyroidism is defined by a reduction in the secretion of PTH. This condition is normally characterized by low calcium levels and elevated phosphate levels in response to the lack of PTH. Not only are calcium levels unusually low, but phosphate levels are unusually high as well, which complicates this condition because phosphate ties up some of the free calcium.

Hypoparathyroidism can also have primary and secondary causes. Primary hypoparathyroidism is known to have two separate origins. The most common is a decrease in PTH release caused by accidental removal of the parathyroid gland. The other is damage of the blood supply around the parathyroid glands. Both occur after there has been some type of surgery or other medical procedure in the neck area. Consequently, the decline in PTH results in low calcium and elevated phosphate concentrations.

Secondary hypoparathyroidism is a frequent complication of
cirrhosis and is characterized by a decrease in both calcium and magnesium concentration. Because magnesium is essential for the release of PTH, this condition can be corrected with magnesium replacement.

Complications associated with all types of hypoparathyroidism include hyperventilation, convulsions, and in some cases tetany of the muscle cells.

Treatment and Therapy

The treatments for primary hyperparathyroidism vary and are dependent on the severity of the condition. Specific drugs can be prescribed that lower elevated blood calcium. Hormone therapy, which includes the administration of estrogen, also acts to restore calcium to normal. Other treatments include dietary calcium restriction and/or surgery to remove the abnormal parathyroid tissue.

Treatment of secondary hyperparathyroidism often involves correcting the problems associated with kidney failure. This can be done by administration of a dietary calcium supplement to restore plasma calcium levels or, in more severe cases, by kidney transplantation. Vitamin D therapy has also been attempted for those patients diagnosed in the early stages of
renal failure.

Hypoparathyroidism is usually treated with dietary calcium and vitamin D supplementation. Both of these treatments promote calcium absorption and decrease calcium loss. The duration of the treatment depends on the severity of the condition and may last a lifetime.

Bibliography

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