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P A R T 6  Drugs acting on the endocrine system

the day and fall to low levels by evening. At this point, the hypothalamus and pituitary sense low levels of the hormones and begin the production and release of CRH and ACTH again. This peaks around midnight and the cycle starts again. Activation of the stress reaction through the SNS bypasses the usual diurnal rhythm and causes release of ACTH and secretion of the adrenocortical hormones— an important aspect of the stress response. The stress response is activated with cellular injury or when a person perceives fear or feels anxious. These hormones have many actions, including the following: • Increasing the blood volume (aldosterone effect) • Causing the release of glucose for energy • Slowing the rate of protein production (which preserves energy) • Blocking the activities of the inflammatory and immune systems (which preserves a great deal of energy) These actions are important during an acute stress situation, but they can cause adverse reactions in periods of extreme or prolonged stress. For instance, a post­ operative person who is very fearful and stressed may not heal well because protein building is blocked; infec- tions may be hard to treat in such an individual because the inflammatory and immune systems are not function- ing adequately. Aldosterone is also released without ACTH stimu­ lation when the blood surrounding the adrenal gland is high in potassium, a direct stimulus for aldosterone release. Aldosterone causes the kidneys to excrete potas- sium to restore homeostasis. Adrenal Insufficiency Some individuals can experience a shortage of adreno­ cortical hormones and develop signs of adrenal insufficiency (Table 36.1). This can occur when a person does not produce enough ACTH, when the adrenal glands are not able to respond to ACTH, when an

adrenal gland is damaged and cannot produce enough hormones (as in Addison’s disease) or secondary to surgical removal of the glands. A more common cause of adrenal insufficiency is prolonged use of corticosteroid hormones. When exog- enous corticosteroids are used, they act to negate the regular feedback systems (Figure 36.1). The adrenal glands begin to atrophy because ACTH release is sup- pressed by the exogenous hormones, so the glands are no longer stimulated to produce or secrete hormones. It takes several weeks to recover from the atrophy caused by this lack of stimulation. To prevent this from hap- pening, people should receive only short-term steroid therapy and should be weaned slowly from the hormones so that the adrenals have time to recover and start pro- ducing hormones again. Adrenal crisis Individuals who have an adrenal insufficiency may do quite well until they experience a period of extreme stress, such as a motor vehicle accident, a surgical procedure or a massive infection. Because they are not able to supple- ment the energy-consuming effects of the sympathetic reaction, they enter an adrenal crisis, which can include physiological exhaustion, hypotension, fluid shift, shock and even death. Individuals in adrenal crisis are treated with a massive infusion of replacement steroids, constant monitoring and life support procedures. ■■ There are two adrenal glands, one on top of each kidney. ■■ Each adrenal gland is composed of the adrenal medulla and the adrenal cortex. ■■ Corticosteroids help the body to conserve energy for the stress response. ■■ Prolonged use of corticosteroids suppresses the normal hypothalamic–pituitary axis and leads to adrenal atrophy from lack of stimulation. KEY POINTS

■■ TABLE 36.1 Signs and symptoms of adrenal dysfunction Clinical effects Hypoadrenal function (Addison’s syndrome)

Hyperadrenal function (Cushing’s disease)

Central nervous system Cardiovascular system Skin, hair, nails

Confusion, disorientation

Emotional disturbances

Hypotension, arrhythmias, cardiovascular collapse, loss of extracellular fluid Hyperpigmentation, sparse axillary and pubic hair; bluish-black oral mucosa Hyponatraemia, hyperkalaemia, hypoglycaemia; lethargy, fatigue, weakness Dehydration, fatigue, poor response to stress, limited ability to respond to infection

Cardiac hypertrophy, hypertension

Thin, wrinkled skin; purpura; purple abdominal striae; hirsutism Hyperglycaemia, hypokalaemia; hypernatraemia; osteoporosis; renal calculi; amenorrhoea Moon face; buffalo hump; obesity; immune and inflammatory suppression; risk of gastric ulcers and bleeding

Metabolic rate

General