- Traditional endocrinology
- Function of the endocrine system
- Glands and hormones of the human endocrine system
- Growth and development
- Endocrine-related developmental disorders
- Ectopic hormone and polyglandular disorders
- Endocrine changes with aging
Acquired and congenital endocrine hypofunction
Endocrine glands may be destroyed in a variety of ways, but complete destruction is unusual. For most endocrine glands, at least 90 percent of the gland must be destroyed before major signs of hormone deficiency become apparent. There are many acquired causes of endocrine hypofunction. In the case of paired endocrine glands, such as the adrenal glands and the gonads, the removal of one of the pair is followed by a compensatory increase in the activity and the size of the remaining gland, which allows normal hormone levels to be maintained. In the case of physical trauma, including surgical trauma and severe hemorrhage within the gland, gland destruction may occur, which leads to endocrine hypofunction. Other acquired causes of endocrine hypofunction include infiltration by cancer cells or inflammatory cells; accumulation of large amounts of a metal (e.g., iron) or an abnormal protein (e.g., amyloid); bacterial, fungal, and viral infections; and damage from X-rays or radioactive elements.
Congenital defects or deficiencies can also cause endocrine gland hypofunction. Congenital endocrine gland hypofunction may be due to incomplete endocrine gland formation during fetal development or an inherited genetic mutation that causes deficiency of an enzyme needed for hormone synthesis, deficiency of substances needed for hormone production, or deficiency of receptors on target organs that leads to reduced hormonal action. In addition, congenital endocrine gland hypofunction may be caused by drugs or other substances that are absorbed through the placenta, thereby blocking fetal hormone production and maternal hormone signaling. Since these disorders affect the primary source of particular hormones, they result in a set of conditions designated as primary endocrine gland hypofunction.
Autoimmune endocrine hypofunction
Perhaps the single most common cause of endocrine hypofunction is autoimmunity. In autoimmune disorders, immune cells such as lymphocytes function improperly, producing antibodies that react with the body’s own tissues instead of with foreign substances (see immune system; immune system disorder). In the endocrine system, autoimmune components act on and usually alter an endocrine gland’s function. For instance, in the case of the thyroid gland, antibodies may be cytotoxic (cell-killing), damaging and eventually destroying the thyroid cells; inhibitory, blocking the binding of thyrotropin to its receptors on thyroid cells and preventing the action of thyrotropin; or stimulatory, mimicking the action of thyrotropin and causing thyroid hyperfunction. In some situations, cytotoxic lymphocytes will themselves infiltrate and attack the thyroid gland.
Secondary endocrine hypofunction
Secondary hypofunction is a distinct category of endocrine gland hypofunction in which the gland is basically intact but is dormant because it either is not stimulated or is directly inhibited. This form of hypofunction is reversible in that the gland begins working normally again if the stimulating hormone is supplied or if the inhibiting hormone or agent is removed. An example of secondary endocrine hypofunction is the loss of a stimulating (tropic) hormone that occurs as a result of pituitary gland destruction. In this situation, hormones are lost in a sequential order, beginning with growth hormone, followed by the gonadotropins, and followed by thyrotropin and adrenocorticotropin. Ultimately, there is growth failure and hypofunction of the gonads, thyroid gland, and adrenal glands.
Other causes of endocrine hypofunction
Changes in biochemical environments may lead to endocrine hypofunction. A well-characterized example is the nutritional deficiency state caused by iodine deficiency. Iodine is an integral part of the thyroid hormone molecule, and it must be obtained from the diet. Hypothyroidism, a decrease in available thyroid hormone, is common in areas of the world in which iodine levels in the soil are low and therefore the foods that are produced and consumed as the mainstay of the diet in those areas contain very small amounts of iodine. Drugs may also cause endocrine hypofunction. For example, patients with bipolar disorder are often treated with lithium, a drug that blocks thyroid hormone synthesis. Excess of one hormone that leads to the deficiency of another hormone can cause endocrine hypofunction. For example, overproduction of prolactin, a pituitary hormone, results in a secondary suppression of gonadal function, leading to amenorrhea in women and impotence in men. These changes are reversed when the serum concentration of prolactin is reduced to normal.
Hormone deficiency can also occur as a result of defective hormonal action on target organs. This concept was first proposed in 1942 by American clinical endocrinologist Fuller Albright. Albright and his colleagues studied a young woman who had signs of parathormone deficiency but who, unlike other patients with parathormone deficiency, did not improve after the injection of an extract prepared from parathyroid glands. Albright termed this disorder pseudohypoparathyroidism and postulated that the disturbance is not a lack of parathormone but “an inability to respond to it.” Direct evidence supporting this suggestion emerged decades later, and many other examples of unresponsiveness of target tissues to hormones have been documented since then. For example, an absence of androgen receptors causes people who are genetically male to appear to be female. In another example, some patients with diabetes mellitus do not respond to large quantities of insulin because they lack effective insulin receptors on target cells in the pancreas. In rare instances, a structurally abnormal hormone will not be recognized by its receptors on target cells, resulting in reduced biological activity of the hormone.
Endocrine hypofunction was once believed to be a cause of aging; however, the only well-documented endocrine hypofunction associated with age is the loss of ovarian hormones leading up to and during menopause. Even in postmenopausal women, however, the ovaries continue to produce small amounts of estrogens. In addition, there is a decline in the production of pituitary growth hormone and adrenal androgen with age in women and men and a decline in testicular function with age in men. For most other endocrine glands there may be no change or only a very small decrease in function. Whether the changes have survival value (or harm) is not clear.