Parathyroid hormone

Parathyroid hormone, PTH, is produced by the parathyroid glands (four small glands in the neck, behind the thyroid gland). It plays a crucial role in bone remodelling process, the continuous process of bone tissue renewal throughout life. Underactive (hypoparathyroidism) or overactive (hyperparathyroidism) levels of PTH thus cause bone diseases, and other problems from too high (hypercalcaemia) or too low (hypocalcaemia) concentrations of Ca2+ ions in the blood. Such problems include damage to the kidneys or mineral deposits in the lens of the eye.

PTH is secreted whenever the blood serum levels of Ca2+ ions are low or falling, it activates the osteoclasts (cells responsible for breaking down old bone tissue in the renewal process), leading to a release of Ca2+ ions from bone into the blood to normalise the amount of calcium ions in circulation. The maintenance of stable Ca2+ concentrations in blood serum, is regulated by multiple feedback and control cycles. PTH has a counter-player hormone, calcitonin that is secreted by the thyroid gland whenever the Ca2+ levels in the blood are too high or rising and which inhibits the mobilisation of Ca2+ by bone resorption. Maintaining equilibrium Ca2+ levels in the blood is a delicate balancing act as the amount of calcium ions in ‘store’ in bone is approximately 3,000 times more than the amount of calcium ions dissolved in blood. In addition, the mobilised amount of calcium ions in circulation not only depends on the interplay of PTH and calcitonin but also on external factors such as variations in nutrition and metabolism, as well as stress (PTH secretion is triggered by adrenaline and histamine) and sleep patterns. In addition to the regulation of Ca2+ concentrations, PTH is also an active part of the body’s phosphate metabolism and activates the promotion of pro-vitamin D to its active form, vitamin D (in the kidneys).

The serum concentration of PTH can be determined by a range of blood tests; it needs to be in a fairly narrow concentration range to ensure normal physiological function.

Excessive amounts of PTH in the blood (hyperparathyroidism) can be caused by overactivity of the parathyroid glands, or by abnormally low Ca2+ blood concentrations (hypocalcaemia) from other causes. Hyperparathyroidism is normally treated by surgical removal of most of the overactive gland tissue, sometimes supported by medication (such as calcimimetics - drugs that mimic calcium ions in blood) or oestrogen hormone replacement therapy in post-menopausal women; bisphosphonates also reduce the loss of Ca2+ ions from osteoporosis caused by hyperparathyroidism. All these medications have potentially serious risks for long-term use and do not address any underlying problem of the parathyroid glands.

Insufficient amounts, or complete lack, of PTH in blood serum (hypoparathyroidism) are most commonly caused by damage to, or removal of, the parathyroid glands in thyroid surgery. The traditional treatment for hypoparathyroidism was to use calcium and vitamin D supplements to normalise blood serum levels. This therapy did not restore the normal regulation and maintenance of Ca2+ (and phosphate) metabolism. It affected the quality of life and increased the risk for the development of a number of comorbidities. Nowadays, PTH replacement therapy is used, most commonly by daily injections of a very close analogue of human PTH.