Addison's disease, Cushing's syndrome, aldosteronism, adrenal virilism and the related mixed syndromes are known diseases of the adrenal glands and will not be discussed here. We are concerned with the role of the adrenal cortex in the "diseases of adaptation."

Four principal lines of evidence support an interest in the problem. First, ACTH, cortisone, hydrocortisone and certain synthetic derivatives of hydrocortisone can suppress the symptoms of a large number of human diseases, most of which are classified as inflammatory diseases. The growth of some cancers can be retarded by these hormones. There is no satisfactory evidence that the hormones cure these diseases or that these diseases represent any form of adrenocortical insufficiency. Second, removal of the adrenal glands may be followed by amelioration of diabetes, hypertension and certain cancers in experimental animals and in patients. Third, overdosing of experimental animals with one or another corticoid can cause a great deal of interesting pathology, including steroid diabetes, hypertension, arteriosclerosis, gastrointestinal ulcers, nephritis, nephrosclerosis, periarteritis nodosa, etc. Resistance to infectious agents is dramatically decreased in animals and patients with severe hypercorticalism. Fourth, as discovered by Skelton,3 enucleation of the adrenal glands of the sensitized rat (unilateral nephrectomy, high sodium load) is followed by hypertension and renal and cardiovascular lesions. These lines of evidence can be interpreted as supporting the Selye concept of the role of the adrenal cortices in the etiology of the "adaptation disease" when linked with the information that many stressful situations cause at least a temporary increase in the secretory activity of the adrenal cortices.

The first weakness of the Selye concept is that most of the supporting evidence is derived from conditions which do not occur naturally. The second weakness is the absence of any convincing experimental evidence that naturally occurring stressors can cause "adaptation diseases" under naturally occurring conditions. Even if such evidence were available, it would remain to be shown that the adrenal glands must be present in order for the disease to be produced.

The remainder of this paper is an account of our own studies and ideas on the role of the adrenal glands in the metabolic responses to stress and in the etiology of experimentally induced diseases.