15.05 Drugs used to treat adrenal cortex disorders

The adrenal glands sit above the kidneys and comprise of 2 sub-sections the adrenal medulla, which produces catecholamines (adrenaline) and the adrenal cortex which synthesises the corticosteroids. Corticosteroids are involved in a wide range of physiologic processes including the stress response, immune response, regulation of inflammation, carbohydrate metabolism, proteincatabolism, blood electrolyte levels, and behaviour. The adrenal cortex hormones are synthesised from cholesterol and released from the adrenal cortex and can be classed as glucocorticoids, mineralocorticoids or androgens.

Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory, immunosuppressant and important for resistance to stress. Mineralocorticoids such as aldosterone control fluid and electrolyte balance, sodium and water retention. Androgens are the precursor of male and female sex hormones. These are important for the regulation of reproduction and the development of the sex organs.

Cushing's syndrome (also known as hyperadrenocorticism or hypercorticism) is caused by elevated cortisol levels in the blood. Cushing's disease specifically involves a tumour (adenoma) in the pituitary gland that produces large amounts of adenocorticotrophic hormone (ACTH), which then elevates cortisol. The most common cause of Cushing's syndrome is exogenous administration of systemic glucocorticoids prescribed to treat other diseases (called iatrogenic Cushing's syndrome). Examples would include systemic glucocorticoid treatment for rheumatoid arthritis or for immunosuppression after an organ transplant.

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Additional fat deposited on the back of the neck (buffalo hump) and a round or "moon face" is common. Other symptoms include excessive sweating, proximal muscle weakness (hips, shoulders) and hirsutism (due to increased androgen production), osteoporosis, amenorrhea, impotence diabetes mellitus and stunted growth.

Addison’s disease (also known as adrenal insufficiency, hypoadrenalism, hypocortisolism) is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones (glucocorticoids and mineralocorticoids). It is characterised by a number of relatively nonspecific symptoms, such as abdominal pain and weakness. Other symptoms include fatigue, postural hypotension, muscle pain and weakness, fever, weight loss, difficulty in standing up, anxiety, gastro-intestinal problems, headache, sweating, mood and personality changes. Causes of Addison’s disease include autoimmune damage of the adrenal gland, or a surgical bilateral adrenalectomy (due to tumour) or hypopituitarism, where insufficent ACTH is produced by the pituitary gland. Adrenal insufficiency may progress to Addisonian crisis, a severe illness resulting in marked hypotension and coma.

Treatment for iatrogenic Cushing’s syndrome involves tapering down the glucocorticoid treatment causing the problem. Surgery is required to remove the tumour-related causes of Cushing’s syndrome. Removal of the adrenal glands would then require replacement with a glucocorticoid (e.g. cortisone) and a mineralcorticoid e.g. fludrocortisone. Treatment of Addison’s disease also involves life-long replacement of adrenal hormones e.g. cortisone and fludrocortisone.

The glucocorticoids are also used in the treatment of bronchial asthma (eChapter 17) and in the treatment of other inflammatory conditions. The aldosterone antagonist spironolactone is used in the treatment of heart failure (eChapter 12).