A Textbook of Clinical Pharmacology and Therapeutics

●Adrenal cortex 302 ●Adrenal medulla 305

CHAPTER 40

40 Adrenal hormones

ADRENAL CORTEX

The adrenal cortex secretes:

1. glucocorticosteroids, principally cortisol (hydrocortisone);
   2.mineralocorticoids – principally aldosterone;
   3.androgens (relatively small amounts).

GLUCOCORTICOSTEROIDS

The actions of glucocorticosteroids and the effects of their over-
secretion (Cushing’s syndrome) and under-secretion (Addison’s
disease) are summarized in Table 40.1. Glucocorticosteroids
influence carbohydrate and protein metabolism, and play a
vital role in the response to stress. Glucocorticosteroids stimu-
late the mobilization of amino acids from skeletal muscle, bone
and skin, promoting their transport to the liver where they are
converted into glucose (gluconeogenesis) and stored as glyco-
gen. Fat mobilization by catecholamines is potentiated by
glucocorticosteroids. The major therapeutic uses of the gluco-
corticosteroids exploit their powerful anti-inflammatory and
immunosuppressive properties. They reduce circulating
eosinophils, basophils and T-lymphocytes, while increasing
neutrophils. Applied topically to skin or mucous membranes,
potent steroids can cause local vasoconstriction and massive
doses administered systemically can cause hypertension due to
generalized vasoconstriction.

Mechanism of action

Glucocorticosteroids combine with a cytoplasmic glucocortico-
steroid receptor causing its dissociation from a phosphorylated
heat shock protein complex. The receptor–glucocorticosteroid
complex translocates to the nucleus, where it binds to gluco-
corticosteroid response elements (GREs) in DNA and acts as a
transcription factor. This increases the transcription of various
signal transduction proteins. In addition, the glucocortico-
steroid receptor interacts with both NFκB and AP-1 and inhibits
them from enhancing transcription of many pro-inflammatory

proteins. Thus glucocorticosteroids produce a delayed but pro-

found anti-inflammatory effect.

Adverse effects

Adverse effects of glucocorticosteroids are common to all

members of the group, and will be discussed before consider-

ing the uses of individual drugs.

Chronic administration causes iatrogenic Cushing’s syn-

drome (see Table 40.1). Features include:

• Cushingoid physical appearance;


• impaired resistance to infection;


• salt and water retention; hypokalaemia;


• hypertension;


• hyperglycaemia;


• osteoporosis;


• glucocorticosteroid therapy is weakly linked with peptic
  ulceration, and can mask the symptoms and signs of
  gastrointestinal perforation;


• mental changes: anxiety, elation, insomnia, depression
  and psychosis;


• posterior cataracts;


• proximal myopathy;


• growth retardation in children;


• aseptic necrosis of bone.
  Acute adrenal insufficiency can result from rapid withdrawal
  after prolonged glucocorticosteroid administration. Gradual
  tapered withdrawal is less hazardous. However, even in
  patients who have been successfully weaned from chronic treat-
  ment with glucocorticosteroids, for one to two years afterwards
  a stressful situation (such as trauma, surgery or infection) may
  precipitate an acute adrenal crisis and necessitate the adminis-
  tration of large amounts of sodium chloride, glucocorticos-
  teroids, glucose and water. Suppression of the adrenal cortex is
  unusual if the daily glucocorticosteroid dose is lower than the
  amount usually secreted physiologically. The rate at which
  patients can be weaned off glucocorticosteroids depends on
  their underlying condition and also on the dose and duration of
  therapy. After long-term glucocorticosteroid therapy has been
  discontinued the patient should continue to carry a steroid card
  for at least one year.