C H A P T E R 3 6
Adrenocortical agents
537
A
drenocortical agents are widely used to suppress the
immune system. These drugs do not, however, cure any
inflammatory disorders. Once widely used to treat a
number of chronic problems, adrenocortical agents are
now reserved for short-term use to relieve inflammation
during acute stages of illness or for replacement therapy
to maintain hormone levels when the adrenal glands are
not functioning adequately.
THE ADRENAL GLANDS
The two adrenal glands are flattened bodies that sit on
top of each kidney. Each gland is made up of an inner
core called the
adrenal medulla
and an outer shell called
the
adrenal cortex
.
The adrenal medulla is actually part of the sympa-
thetic nervous system (SNS). It is a ganglion of neurons
that releases the neurotransmitters noradrenaline and
adrenaline into circulation when the SNS is stimulated.
(See Chapter 29 for a review of the sympathetic nervous
system.) The secretion of these neurotransmitters
directly into the bloodstream allows them to act as
hormones, travelling from the adrenal medulla to react
with specific receptor sites throughout the body. This
is thought to be a backup system for the sympathetic
system, adding an extra stimulus to the stress (“fight-or-
flight”) response.
The adrenal cortex surrounds the medulla and
consists of three layers of cells, each of which synthesises
chemically different types of steroid hormones that exert
physiological effects throughout the body. The adrenal
cortex produces hormones called
corticosteroids
. There
are three types of corticosteroids: androgens, gluco
corticoids and mineralocorticoids. Androgens are a
form of the male sex hormone testosterone. They affect
electrolytes, stimulate protein production and decrease
protein breakdown. They are used pharmacologically
to treat hypogonadism or to increase protein growth
and red blood cell production. These hormones are dis-
cussed in Chapter 41.
Controls
The adrenal cortex responds to adrenocorticotropic
hormone (ACTH) released from the anterior pituitary.
ACTH, in turn, responds to corticotropin-releasing
hormone (CRH) released from the hypothalamus. This
happens regularly during a normal day in what is called
diurnal rhythm
(Box 36.1). A person who has a regular
cycle of sleep and wakefulness will produce high levels of
CRH during sleep, usually around midnight. A resulting
peak response of increased ACTH and adrenocortical
hormones occurs sometime early in the morning, around
6 to 9 a.m. This high level of hormones then suppresses
any further CRH or ACTH release. The corticoster-
oids are metabolised and excreted slowly throughout
Diurnal rhythm
Research over the years has shown that the adrenocortical
hormones are released in a pattern called the diurnal
rhythm.The secretion of corticotropin-releasing hormone
(CRH), adrenocorticotropic hormone (ACTH) and cortisol
are high in the morning in day-oriented people (those
who have a regular cycle of wakefulness during the day
and sleep during the night). In such individuals, the peak
levels of cortisol usually come between 6 and 8 a.m.
The levels then fall off slowly (with periodic spurts) and
reach a low in the late evening, with lowest levels around
midnight. It is thought that this cycle is related to the
effects of sleeping on the hypothalamus, and that the
hypothalamus is regulating its stimulation of the anterior
pituitary in relation to sleep and activity.The cycle may
also be connected to the hypothalamic response to light.
This is important to keep in mind when treating people
with corticosteroids. In order to mimic the normal diurnal
pattern, corticosteroids should be taken immediately on
awakening in the morning.
Complications to this pattern arise, however, when
people work shifts or change their sleeping patterns
(e.g. university students). In response, the hypothalamus
shifts its release of CRH to correspond to the new cycle.
For instance, if a person works all night and goes to bed at
8 a.m., arising at 3 p.m. to carry on the day’s activities before
going to work at 11 p.m., the hypothalamus will release CRH
at about 3 p.m. in accordance with the new sleep–wake
cycle. It usually takes 2 or 3 days for the hypothalamus
to readjust. A person on this schedule who is taking
replacement corticosteroids would then need to take them
at 3 p.m., or on arising. People who work several different
shifts in a single week may not have time to reregulate
their hypothalamus, and the corticosteroid cycle may be
thrown off. People who have to change their sleep patterns
repeatedly often complain about feeling weak, getting sick
more easily, or having trouble concentrating. University
students frequently develop a pattern of sleeping all day,
then staying up all night—a cycle that becomes hard to
break as their bodies and endocrine systems try to readjust.
It is a challenge to help people understand how the
body works and to offer ways to decrease the stress
of changing sleep patterns—especially if the health
professional is also working several different shifts. Many
employers are willing to have employees work several
days of the same shift before switching back, mainly
because they have noticed an increase in productivity and
a decrease in absences when employees have enough
time to allow their bodies to adjust to the new shift.
The evidence
BOX 36.1
