Tests of adrenal cortical function and their place in the diagnosis of adrenal cortical disease.

Tremendous advances have taken place in our understanding of the function of the adrenal glands in health and in disease. In the last decade biochemists have isolated and synthesized numerous hormones secreted by the cortex, while clinical endocrinologists have applied this knowledge in elucidating the various syndromes associated with adrenal disease. Tests of adrenal function tend to be based as directly as possible on the hormonal output of the cortex and, since these hormones are complex and difficult to estimate in the blood, recent work has been concerned with methods of estimating breakdown products of the hormones in the urine. Although some 30 compounds have been isolated from the adrenal cortex, only a few of them have been shown to exert physiological activity. These physiologically active hormones can be divided into three main groups: i. Glucocorticoids. This group contains hydrocortisone and cortisone (I7-hydroxycorticosteroids) as well as corticosterone and iI-dehydrocorticosterone (I I-oxycorticosteroids). All can lead to gluconeogenesis, but the last pair lack antiinflammatory action. The cortisone group, of which hydrocortisone is the main natural secretion, can be estimated in the urine as 17-hydroxycorticoids. Methods of estimating the corticosterones involve hydrolysis and the conversion of I7-hydroxycorticoids to II-oxycorticoids, so that the estimation of i-oxycorticoids represents both the cortisone and the corticosterone groups. The main actions of the cortisone group are now well recognized and can be reproduced either by injecting corticotrophin, which leads to an increased endogenous secretion of hydrocortisone, or by the administration of cortisone by mouth. These actions are: (a) Increased gluconeogenesis. Amino-acids are deaminated and take part in the synthesis of glycogen. This leads to an increase in blood sugar and, if maintained, diabetes can result. (b) An increased breakdown of protein with a negative nitrogen balance. This action may be responsible for reducing bone osteoid formation and for the resulting osteoporosis with loss of body calcium. (c) Retention of sodium and loss of potassium, though to a much lesser extent than with the mineralocorticoid group. (d) Mild androgenic effects leading to acne, hirsutism and red striae. (e) Suppression of processes of inflammation and allergy. (f) Depression of circulating eosinophils. (g) Increased ability to excrete a water load. In disease processes of the adrenal cortex involving primarily the glucocorticoid group disorders of these actions lead to clinical changes which can be demonstrated by suitable tests. Although methods are available for estimating I7-hydroxycorticoids in the blood, determinations are difficult and do no more than reflect a transitory state in what may be a fluctuating output. For these reasons urinary estimations are more generally used and, although methods may well change in the near future, two are in general and current use: