Function of Parathyroid Hormone
Parathyroid hormone functions to maintain calcium homeostasis by elevating concentrations through a variety of mechanisms when calcium-sensing receptors detect a drop in serum levels (Griffin & Ojeda, 2004). PTH also functions to decrease concentrations of phosphate ions by reducing phosphate reabsorption in kidney tubules; thus levels are lowered when phosphate is lost in urine (Hadley & Levine, 2006).
In order to raise serum Ca2+ and lower PO4-3, parathyroid hormone acts either directly or indirectly through mechanisms that incorporate bone, kidney and intestines (Hadley & Levine, 2006). These actions can be categorized as follows:
PTH on bone
PTH plays a role in mineral metabolism in order to raise serum calcium should it become low. As PTH is known to release calcium from bone into plasma, at first it seems counterintuitive that stromal osteoblast cells of the bone marrow are stimulated in the presence of the hormone. However, in response to PTH the osteoblast cells will increase expression of RANKL, a molecule that will bind to the RANK receptor on osteoclast precursor molecules, causing them to differentiate into mature cells. The creation of new osteoclasts increases bone resorption, a process that releases free Ca2+ to the serum (Hadley & Levine, 2006). This breakdown of bone, or osteolysis, also releases phosphate into circulation, but at lesser amounts than that of phosphate leaving the body through excretion.
PTH on renal tubules of the kidney
Parathyroid hormone also increases reabsorption of calcium in the proximal tubule of the kidney (Hadley & Levine, 2006).
PTH on intestine, indirectly through kidney
PTH stimulates the kidney to activate vitamin D by up-regulating the enzyme responsible for converting 25-hydroxy vitamin D, to its active form (1,25-dihydroxy vitamin D) in a hydroxylation reaction (Griffin & Ojeda, 2004). The active form of vitamin D is then able to absorb more calcium in the intestine.
Pathology
Hyperparathyroidism:
Overactivity of one or more parathyroid glands leading to excessive PTH secretion (Griffin & Ojeda, 2004). The excess PTH causes a marked increase in bone resorption and calcium absorption in the intestine leading to hypercalcemia in the blood as well as low phosphate levels.
Symptoms include those connected to high plasma calcium levels, for example, renal stones as a result of excessive calcium in the kidney and neurological symptoms since calcium plays such a large role in the nervous system. Weak bones and osteoporosis-like state are also associated with hyperparathyroidism due to a net resorption of minerals from the bones.
Causes include adenomas or PTH-secreting tumors, classified as primary hyperparathyroidism, overactive osteoclasts or a significantly higher production of active vitamin D than normal. In this case, the overactive gland can be surgically removed or calcitonin supplements given to maintain calcium homeostasis.
Hyperparathyroidism effects
Hypoparathyroidism:
Decreased activity of parathyroid glands resulting in low PTH levels and hypocalcemia (Griffin & Ojeda, 2004).
Low serum calcium can be dangerous because most cells, including neurons, require calcium to exert any effect on bodily functions. Thus, many neurological and neuromuscular symptoms are seen, such as seizures, nerve and skin pain, tetany of muscles and muscles spasms, including those muscles in the pharynx.
Hypoparathyroidism can result due to the accidental removal of one or more parathyroid glands during surgery (i.e. during a thyroidectomy). Autoimmune disorders may result in destruction of the parathyroid glands as well as affecting other organs. DiGeorge syndrome is a genetic disorder resulting in deletion of the locus coding parathyroid glands. A severe vitamin D deficiency can also result in hypoparathyroidism, and is reversible by increasing vitamin D consumption. Idiopathic forms also exist and are caused by an autosomal recessive inheritance pattern. In addition, pseudohypoparathyroidism results in the same lowered blood calcium, but it is due to the target organs upon which PTH acts being resistant to the hormone. Diet modifications are important in treatment, and intravenous calcium may be given with caution.
References:
Griffin, J. E., Ojeda, S. R. 2004. Textbook of Endocrine Physiology. Oxford University Press, New York.
Hadley, M. E., Levine, J. E. 2006. Endocrinology, 6th Ed. Pearson Prentice Hall, New Jersey.
