The Thyroid and Parathyroids
The thyroid gland is a double-lobed structure located in the neck. Embedded in its rear surface are the four parathyroid glands.
The thyroid gland synthesizes and secretes:
- thyroxine (T4)
- triiodothyronine (T3)
- calcitonin
T4 and T3
T4 and T3 are derivatives of the amino acid tyrosine with three (T3) or four (T4) atoms of iodine.
These two hormones have many effects on the body. Among the most prominent of these are:
- an increase in metabolic rate (seen by a rise in the uptake of oxygen)
- an increase in the rate and strength of the heart beat
The cells responsible for the synthesis and release of T4 and T3 take up circulating iodine from the blood. This action as well as the synthesis of the hormones is stimulated by the interaction of TSH on transmembrane receptors at the cell surface.
1. hypothyroid diseases; caused by inadequate secretion of thyroid hormones
- cretinism: hypothyroidism in infancy and childhood leads to stunted growth and intelligence. Can be corrected by giving thyroxine if started early enough.
- myxedema: hypothyroidism in adults leads to lowered metabolic rate and vigor. Corrected by giving thyroxine.
- goiter: enlargement of the thyroid gland. Often caused by inadequate iodine in the diet with resulting low levels of T4 and T3.
Why should a hypothyroid disease produce an enlarged gland?
The activity of the thyroid is under negative feedback control:
- the synthesis and release of TRH and TSH is normally inhibited as the levels of T4 and T3 rise in the blood.
- When the iodine supply is inadequate, T4 and T3 levels fall
- this stimulates the hypothalamus and pituitary to increased TRH and TSH activity respectively. This stimulates the thyroid gland to enlarge (fruitlessly).
The symptoms of hypothyroidism can also result from inherited mutations in the genes encoding:
- the receptor for TSH (present on the surface of thyroid cells) or
- the receptor for T3 (present in the nucleus of almost all cells)
The T3 receptor is a protein located within the nucleus. When it binds its ligand, T3, it becomes a transcription factor binding to the thyroid response element in the promoters of the many genes whose expression is influenced by thyroid hormones.
2. hyperthyroid diseases; caused by excessive secretion of thyroid hormones
Graves´ disease. Autoantibodies against the TSH receptor bind to the receptor mimicking the effect of TSH binding. Result: excessive production of thyroid hormones. Graves´ disease is an example of an autoimmune disease.
Calcitonin is a polypeptide of 32 amino acids.
The thyroid cells in which it is synthesized have receptors that bind calcium ions (Ca2+) circulating in the blood. These cells monitor the level of circulating Ca2+. A rise in its level stimulates the cells to release calcitonin.
- bone cells respond by removing Ca2+ from the blood and storing it in the bone
- kidney cells respond by increasing the excretion of Ca2+
Both types of cells have surface receptors for calcitonin.
Because it promotes the transfer of Ca2+ to bones, calcitonin has been examined as a possible treatment for osteoporosis, a weakening of the bones that is a leading cause of hip and other bone fractures in the elderly. Being a polypeptide, calcitonin cannot be given by mouth (it would be digested), and giving by injection is not appealing. However, inhaling calcitonin appears to be an effective way to get therapeutic levels of the hormone into the blood. A synthetic version of calcitonin (trade name = Miacalcin) is now available as a nasal spray.
The parathyroid glands are 4 tiny structures embedded in the rear surface of the thyroid gland. They secrete parathyroid hormone (PTH) a polypeptide of 84 amino acids.
PTH has three functions, all of which increase the concentration of Ca2+ in the blood.
PTH promotes
- release of Ca2+ from the huge reservoir in the bones. (99% of the calcium in the body is incorporated in our bones.)
- reabsorption of Ca2+ from the fluid in the tubules in the kidneys
- absorption of Ca2+ from the contents of the intestine (this action is mediated by calcitriol, the active form of vitamin D.)
Control of the Parathyroids: the calcium receptor
The cells of the parathyroid glands have surface receptors that bind Ca2+ (the same type of receptor is found on the calcitonin-secreting cells of the thyroid and on the calcium absorbing cells of the kidneys). Binding of Ca2+ to this receptor depresses the secretion of PTH and thus leads to a lowering of the concentration of Ca2+ in the blood. Two classes of inherited disorders involving mutant genes encoding the Ca2+ receptor occur:
- loss-of-function mutations with the mutant receptor always "off". Patients with this disorder have high levels of Ca2+ in their blood and excrete small amounts of Ca2+ in their urine.
- gain-of-function mutations with the mutant receptor always "on" (as though it had bound Ca2+). People with this disorder have low levels of Ca2+ in their blood and excrete large amounts of Ca2+ in their urine.
Hyperparathyroidism
Tumors in the parathyroids elevate the level of PTH causing a rise in the level of blood Ca2+ at the expense of calcium stores in the bones. So much calcium may be withdrawn from the bones that they become brittle and break.
Until recently, treatment has been the removal of most - but not all - of the parathyroid tissue (i.e. the goal is the removal of 3 1/2 glands). Now clinical trials have begun on a drug (designated R-568) that mimics the action of calcium on the parathyroids, resulting in a drop in PTH and blood Ca2+ and sparing the calcium stores in the bone.
24 June 1999
