What are corticosteroids?

Structure and Functions

Corticosteroids are steroid hormones produced by the cortex of the adrenal glands. They have several physiological actions, including regulation of glucose, lipid and protein metabolism, regulation of inflammation and the immune response, maintenance of homeostasis during stress, and control of water and electrolyte balance and blood pressure.

Corticosteroids that have their primary effects on glucose metabolism are glucocorticoids, whereas those that have the control of electrolyte and water balance as their main functions are mineralocorticoids. Cortisol is the primary glucocorticoid, although significant amounts of corticosterone and cortisone are secreted. Aldosterone is the primary mineralocorticoid.

Glucocorticoids promote an increase in blood glucose by stimulating the synthesis of glucose (gluconeogenesis). They also stimulate the catabolism of lipids and proteins. Thus, glucocorticoids increase blood glucose and are antagonistic to insulin.

The synthesis of corticosteroids is controlled by adrenocorticotropic hormone (ACTH)
produced by the pituitary gland. corticotropin-releasing hormone (CRH)
produced by the hypothalamus controls the secretion of ACTH. A feedback loop exists so that when cortisol levels are high, the release of CRH and ACTH is inhibited, and when cortisol levels are low, CRH and ACTH are released.

Aldosterone is primarily responsible for the control of salt and water balance by promoting the excretion of potassium and the retention of sodium and water. Through its effect on salt and water balance, aldosterone can increase blood pressure. Plasma levels of aldosterone are controlled by a variety of mechanisms, including plasma volume and potassium ion concentration.

Disorders and Diseases

Addison’s disease results from adrenal insufficiency (hypocortisolism). Although most cases are caused by a disorder of the adrenal glands (primary adrenal insufficiency), some cases are caused by a disorder of the pituitary gland (secondary adrenal insufficiency). An autoimmune disorder that destroys the adrenal cortex is the major cause of primary adrenal insufficiency. Secondary adrenal insufficiency is usually caused by a lack of ACTH. Pituitary tumors, surgical removal of the pituitary, and loss of blood flow to the pituitary are the major causes of secondary adrenal insufficiency. Major symptoms of adrenal insufficiency include loss of appetite, weight loss, fatigue, muscle weakness, and hypotension. Addison’s disease can be diagnosed by administering ACTH and monitoring the adrenal gland’s response by measuring serum and urine cortisol levels. Adrenal insufficiency is treated by oral administration of
hydrocortisone, a synthetic form of cortisol. If aldosterone is also deficient, then fludrocortisone is administered.

Adrenal insufficiency is often caused by a mutation in one of the enzymes synthesizing cortisol. These cases are referred to as congenital adrenal hyperplasia (CAH). Since serum cortisol is low or absent, the pituitary gland stimulates the adrenal gland to produce more cortisol. The precursor steroids and their metabolic products that accumulate can cause varying degrees of virilization of female fetuses and infants. Replacement therapy is the treatment of choice. Surgery to reconstruct the genital organs may be necessary in severe cases.

Hypercortisolism can lead to Cushing’s syndrome. Major symptoms include obesity, osteoporosis, fatigue, hypertension, hyperglycemia, and amenorrhea (absence of menstruation). Cushing’s syndrome may be caused by prolonged use of glucocorticoids or by an overproduction of glucocorticoids by the adrenal glands. The major causes of an overproduction of glucocorticoids are pituitary and adrenal tumors. Diagnosis of Cushing’s syndrome is most commonly made by determining the amount of cortisol in the urine. Cushing’s syndrome can be treated by reducing administered glucocorticoids or by treatment of the tumor causing the disease through surgical removal, radiation, and/or chemotherapy.

Hypoaldosteronism is a condition in which the adrenal cortex does not produce an adequate amount of aldosterone, which results in an inability to control and regulate blood volume and blood pressure. Blood pressure can fall to dangerously low levels.

Synthetic corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone, and dexamethasone have an immunosuppressive effect and are used to treat a variety of chronic autoimmune and inflammatory diseases. They can reduce the pain, swelling, itching, inflammation, and redness associated with arthritis, bursitis, asthma, dermititis, eczema and psoriasis, lupus erythematosus, Crohn’s disease, and various ear, eye, and skin infections and allergic reactions.

Prolonged use of corticosteroids can lead to medically induced Cushing’s syndrome, suppression of the immune system, hypertension, hypokalemia (low serum potassium), and hypernatremia (high serum sodium).

Perspective and Prospects

In 1855, Thomas Addison became the first physician to describe the clinical symptoms of adrenal insufficiency. In the early 1930s, Frank Hartman, Wilbur Swingle, and Joseph Pfiffner were the first to prepare active adrenal extracts capable of treating the symptoms of adrenal insufficiency. By the mid-1930s, Pfiffner, Edward Calvin Kendall, Oskar Wintersteiner, and Tadeus Reichstein had isolated and crystallized some of the adrenal hormones. In 1944, Lewis Sarett became the first to synthesize cortisone. In the late 1940s, Philip Showalter Hench discovered that the administration of cortisone could alleviate the symptoms of arthritis.

In recent years, it has been shown that corticosteroids express their effect by modulating the expression of a variety of genes involved in many physiological functions, including metabolism and the immune or inflammatory response.

Bibliography

"Corticosteroids." NHS, April 18, 2013.

Griffin, James E., and Sergio R. Ojeda, eds. Textbook of Endocrine Physiology. 5th ed. New York: Oxford University Press, 2004.

Lüdecke, Dieter K., George P. Chrousos, and George Tolis, eds. ACTH, Cushing’s Syndrome, and Other Hypercortisolemic States. New York: Raven Press, 1990.

Riedemann, Therese, Alexandre Patchev, Kwangook Cho, and Osborne F. X. Almeida. "Corticosteroids." Molecular Brain 3 (2010): 2–21.

Vaughan, Darracott E., and Robert M. Carey. Adrenal Disorders. New York: Thieme Medical, 1989.

Vinson, Gavin P., Barbara Whitehouse, and Joy Hinson. The Adrenal Cortex. Englewood Cliffs, N.J.: Prentice Hall, 1992.

"What Are Corticosteroids?" healthychildren.org, May 11, 2013.