Hypofunction of the Adrenal Cortex

Adrenal insufficiency may result from hypofunction of the adrenal cortex (primary adrenal insufficiency, Addison s disease) or from a malfunctioning of the hypothalamic-pituitary system (secondary adrenal insufficiency). In treating primary adrenal insufficiency, one should administer sufficient cortisol to diminish hyperpigmentation and abolish postural hypotension these are the cardinal signs of Addison s disease. 

Thomas Addison first reported on hypofunction of the adrenal cortex in 1855. However, it has only been in the last 60 years that many of the disease states that are associated with abnormal adrenal function have been discovered and studied. In general, diseases of this organ are classified as resulting from either hypofunction or hyperfunction of the adrenal cortex. 

Cortisol secretion fluctuates widely throughout the day, and single. serum measurements are of little value in clinical practice. There is a marked diurnal rhythm. Dynamic tests of cortisol production involving stimulation of the adrenal cortex by synthetic ACTH. or of stimulation or suppression of the whole HPA axis, form an important part of investigations of adrenocortical hyper- or hypofunction and are discussed on the following pages. 

Diuretic, Antidiuretic and Local Anesthetic Agents. Aldosterone, a natural hormone of the adrenal cortex promotes retention in the body of sodium and water, and facilitates excretion of potassium. Hence its effect is almost diametrically opposed to diuretics—especially the thiazide diuretics. Aldosterone is much more active in this respect than desoxycorticosterone. and is used in the treatment of Addison s disease, a hypofunction of the adrenal glands. 

Primary adrenocortical hypofunction caused by destruction of the adrenal cortex, for instance by an autoimmune process or by tuberculosis. 

The synacthen stimulation test illustrates the principle behind these tests. In normal persons, administration of synacthen (a synthetic form of ACTH) results in stimulation of the adrenal cortex and a subsequent rise in the plasma cortisol level. When there is adrenocortical hypofunction, as in Addison s disease, the rise in the plasma cortisol level doe not occur or is markedly reduced. 

Drugs with mineralocorticoidlike activity (aldosterone agonists) are frequently administered as replacement therapy whenever the natural production of mineralo-corticoids is impaired. Mineralocorticoid replacement is usually required in patients with chronic adrenocortical insufficiency (Addison disease), following adrenalectomy, and in other forms of adrenal cortex hypofunction. These conditions usually require both mineralocorticoid and glucocorticoid replacement. 

As mentioned in Chapter 1, perhaps the purest form of drug therapy is the replacement of inadequate amounts of an endogenous substance such as a hormone. Any gland that normally secretes a hormone is a potential target for hypofunctioning. Classical examples include Addison s disease (adrenal cortex), dwarfism (anterior pituitary), juvenile-onset insulin-dependent diabetes (pancreas), and hypothyroidism (thyroid). 

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