Low plasma levels of adrenocorticotropic hormone in patients with acute influenza.

Plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in young adults with influenza virus type A (H3N2) infection for whom cultures were positive and in comparable controls without symptoms or other evidence of illness. The mean plasma ACTH level +/- SE in 19 patients with acute influenza was 13.5 +/- 2.1 pg/mL compared with 23 +/- 3.2 pg/mL in 11 controls (P = .02). Mean plasma ACTH levels +/- SE had risen to 21 +/- 4.1 pg/mL in specimens obtained from patients during convalescence. The mean plasma cortisol level +/- SE in patients with acute influenza was 13.7 +/- 1.4 micrograms/dL compared with 10.8 +/- 1.0 micrograms/dL in controls (P = not significant). ACTH levels in individual controls were relatively higher than their cortisol levels, but ACTH levels in patients tended to be lower than cortisol levels in paired specimens. These findings suggest that influenza virus type A infection may have an inhibitory effect on the production or release of ACTH.

The etiology of rheumatoid arthritis.

The etiology of rheumatoid arthritis has been elusive, but it finally seems to be explained by a combination of three factors: (i) a relatively mild deficiency of cortisol, the normal adrenocortical hormone that is essential for normal immunity but which has achieved a bad reputation because of the use of excessive dosages of it or its stronger derivatives, (ii) a deficiency of dehydro-epi-androsterone (DHEA), the chief androgen produced by the human adrenal cortex but which has been little studied, and (iii) infection by organisms such as mycoplasma, which have a relatively low virulence, are difficult to culture in the laboratory, and cause inflammation and destruction of tissue in periarticular and articular areas of immunocompromised hosts. The mild adrenocortical deficiency apparently is sufficient to impair immunity, especially after stress, and permit these organisms to cause inflammatory arthritis. Further studies are necessary to determine optimum therapy, but it will probably include safe physiologic dosages of cortisol and DHEA plus antibiotic treatment of infection by mycoplasma or other causative organisms.

Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story.

The possibility that patients with disorders that improve with administration of large, pharmacologic dosages of glucocorticoids, such as chronic allergies and autoimmune disorders, might have mild deficiency of cortisol production or utilization has received little attention. Yet evidence that patients with rheumatoid arthritis improved with small, physiologic dosages of cortisol or cortisone acetate was reported over 25 years ago, and that patients with chronic allergic disorders or unexplained chronic fatigue also improved with administration of such small dosages was reported over 15 years ago, suggesting that these disorders might be associated with mild adrenocortical deficiency. The apparent reasons for the failure of these reports to be confirmed or mentioned in medical textbooks and the facts needed to restore perspective are reviewed, and the need for further studies of the possible relationship of a mild deficiency of the production or utilization of cortisol and possibly other normal adrenocortical hormones to the development of these disorders is discussed.

Cortisol and immunity.

The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS).