adrenal glands There are two adrenal glands, one sitting on top of each of the
kidneys. They are pyramidal in shape and weigh about 4 g each. Their presence was recognized as early as the late sixteenth century, but it was not until 1805 that Cuvier reported that the adrenal was made up of two regions, the cortex on the outside and an inner medulla. Fifty years later, a Guy's Hospital physician, Thomas Addison, showed that the adrenal glands were necessary for life, by identifying them as the site of damage in a previously mysterious and ultimately fatal illness, which became known as Addison's disease.
The adrenal cortex
is known now to have three distinct regions: the
zona glomerulosa,
zone fasciculata, and
zona reticularis. The first of these regions produces the steroid
aldosterone, while another steroid hormone,
cortisol, is produced by the other two regions. The cells which make up all of these regions are full of lipid droplets containing
cholesterol, which can be converted into the steroid hormones.
Aldosterone,
by acting on the kidneys, controls the
salt content of the body — by which means it also indirectly controls the blood pressure. The amount of aldosterone produced is controlled by other substances, including a protein from the kidney known as
renin. Specialized cells in the kidney, which form the
juxtaglomerular apparatus, are very sensitive to changes in
blood pressure — well placed for this function by being wrapped around arterioles. If there is a fall in blood pressure, for example when getting out of bed in the morning, this is sensed by these cells and they respond by increasing the amount of renin put out into the bloodstream. Renin is an enzyme that converts the protein
angiotensinogen to angiotensin I which is converted to angiotensin II. This in turn stimulates more aldosterone to be produced by the adrenal cortex; the aldosterone acts on the kidneys to retain more
salt, and the salt is followed by
water; both the salt and the water are reabsorbed into the blood and the resulting increase in the volume of the blood helps to restore the blood pressure to normal. Abnormally high production of aldosterone (
hyperaldosteronism) causes excessive retention of salt and water in the body. This results in
oedema and high blood pressure. If insufficient aldosterone is produced (
hypoaldosteronism) there is a loss of water and salt which causes a fall in blood pressure, heart and kidney abnormalities, and general weakness.
Cortisol
acts on cells in many tissues in the body and influences general
metabolism,
blood pressure, and appetite. The amount of cortisol produced is controlled by another hormone,
adrenocorticotrophic hormone (ACTH), secreted by the
pituitary gland. This secretion in turn is controlled by
corticotrophin-releasing hormone (CRH) from the hypothalamus. CRH secretion responds to signals from elsewhere in the brain, but both CRH and ACTH secretion are also influenced by the amount of cortisol in the blood. A major stimulus to this whole sequence of hormone secretions is
stress. The biggest increase in the amount of cortisol produced by the adrenal glands is seen during surgery, although modern anaesthetics minimize the increase. Anxiety such as waiting for the beginning of a race or examinations also causes an increase in cortisol production. Cortisol is therefore a key component of the ‘fight or flight’ reaction of the individual in moments of crisis. The condition of cortisol excess is known as
Cushing's syndrome after Harvey Cushing, the American neurosurgeon who, in 1932, described a condition associated with obesity and stretch marks (
striae) around the abdomen, a round rosy face, hypertension, muscle weakness, diabetes, and increased hair growth on the face and body. These changes are attributable mainly to the action of cortisol on fat and protein in the body, although the growth of hair is due to an excess of the weak androgenic steroids also produced by the adrenal cortex. The features of this condition are associated with the presence of high levels of cortisol in the blood over a long period; it can be due either to overstimulation of the adrenal cortex by an excessive secretion of ACTH from a tumour of the anterior pituitary (the context in which Cushing encountered it), or to an abnormal growth of cortisol-secreting tissue in the adrenals themselves. Prolonged medication with corticosteroids can also mimic the syndrome.
Abnormally
low levels of cortisol (
hypocortisolism), result in a general feeling of being unwell, with tiredness, vomiting, nausea, and weight loss. A person in this condition is unable to cope with stress and liable to collapse with relatively minor injury or insult. Because there is insufficient cortisol in the blood to inhibit the secretion of ACTH, this hormone is produced in very high amounts and causes the skin to become dark or ‘bronzed’.
There can be loss of secretion of both cortisol and aldosterone if there is destruction of the adrenal glands by tumour or infection. This condition is known as
Addison's disease, following its elegant description by Thomas Addison in 1855.
The adrenal medulla
makes up about 10% of the substance of the adrenal glands and is essentially and developmentally a part of the sympathetic division of the autonomic nervous system. It consists of ‘chromaffin cells’ (so named because of their affinity for chromium) and their main product is
adrenaline (also known as
epinephrine), which is involved in the fight or flight reaction along with cortisol. More adrenaline is produced in times of stress, by the stimulating action of sympathetic nerves directly upon the chromaffin cells. Adrenaline was the first hormone to be discovered, in 1894 — an event which encouraged the search for similar chemical mediators in the body, and led to the creation of the specialty of
endocrinology. Unlike cortisol, which is produced exclusively in the adrenal cortex, adrenaline is produced in other parts of the body, including the brain, as well as in the adrenal medulla. Like cortisol, adrenaline has widespread actions at many sites in the body, including the heart, lungs, and blood vessels, facilitating an increase in the supply of nutrients and oxygen. It also redeploys necessary fuels very rapidly, in readiness for immediate action if required: acting for example in the liver to enhance the release of glucose into the blood. However, because adrenaline is produced in other areas of the body, removing the medulla does not seem to be a critical threat to life, though there does seem to be benefit in having adrenaline produced from the medulla at times of acute stress.
Noradrenaline (norepinephrine), better known and most important as a neurotransmitter at sympathetic nerve endings, is also secreted by the medulla, along with adrenaline, but in much smaller amounts.
None of the adrenal hormones are released at a constant rate, but in amounts which change in response to various stimuli throughout the day. In addition, in the case of cortisol and to a certain extent aldosterone, there is a gradual change of background levels in the blood over each 24-hour period. This pattern of release is called a circadian rhythm, and is linked to the sleep–wake cycle of the individual — the ‘
body clock’. In the normal individual the greatest amounts of cortisol are released at about 8 o'clock in the morning; the level in the blood gradually falls during the day so that the lowest levels are found at about midnight. ACTH also shows a circadian rhythm reaching maximum levels in the blood just before those of cortisol. The circadian rhythm of aldosterone is of much smaller amplitude than that of cortisol. Changing the times a person is asleep or awake will change the pattern of secretion; if shift workers sleep during the day and are awake at night then the circadian rhythm will be displaced by about 12 hours, with the highest blood levels of cortisol occurring in the early evening and the lowest levels about mid-day. Similar changes occur when travelling across time zones. The shift in the circadian rhythm occurs gradually over a period of several days
Corticosteroid therapy
Treatment of a variety of conditions by synthetic corticosteroids became common from the latter half of the twentieth century. They have been invaluable in suppressing adverse reactions to curative drugs, such as in the treatment of tuberculosis and other life-threatening illnesses; also in controlling inflammatory and allergic conditions, notably rheumatoid arthritis, asthma, and some skin diseases. It follows, however, from the normal control of cortisol secretion, that when the level of corticosteroids in the blood is deliberately raised by medication, the secretion of ACTH from the pituitary is suppressed. This becomes a problem if treatment is suddenly withdrawn, leaving the person liable to collapse under stress because there is no ACTH to stimulate the adrenal glands to produce their own cortisol.
M. Wheeler
See
endocrine.See also
autonomic nervous system;
body clock;
body fluids;
steroids.
