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The adrenal cortical hormone, cortisone, and the pituitary adrenocorticotropic hormone (ACTH) possess potent antirheumatic properties. Their administration produces strikingly beneficial effects on a number of rheumatic diseases including rheumatoid arthritis, rheumatoid (ankylosing) spondylitis, acute rheumatic fever, disseminated lupus erythematosus, periarteritis nodosa, psoriatic arthritis, dermatomyositis, and gout. In general the effects of these substances are temporary and they cause suppression rather than cure of the disease processes. Improvement is maintained usually only by continuing administration, and on hormonal withdrawal prompt or fairly prompt relapse of the disease manifestations ensues. In addition to their antirheumatic effects cortisone and ACTH influence a wide variety of physiologic functions. Administration of them therefore may produce a number of metabolic and clinical changes, some of which are not advantageous from a therapeutic standpoint. Adverse side-reactions are more liable to occur when large doses of the hormones are given for prolonged periods; such reactions appear to be reversible and disappear when administration of the hormones is stopped. With cortisone, comparatively few untoward signs develop when smaller amounts are administered continuously even for periods of months. Greater clinical experience is needed before optimal doses and schedules of administration are finally determined. It appears that some severe cases, many moderately severe cases, and most moderate and mild cases of rheumatoid arthritis may be adequately controlled with smaller "maintenance" doses of cortisone ranging from 32 to 65 mg. a day, providing larger doses to suppress the disease manifestations are employed initially. Neither cortisone nor ACTH should be considered as a therapeutic agent for general use until more information regarding their physiologic activities and the consequences of prolonged or repeated administration of them are available. Until the potential dangers of these hormones can be determined precisely, the use of them should be considered as an investigative procedure.

Recent experimental evidence suggests that hydrocortisone (Kendall's Compound F) is probably the principal glycogenic steroid secreted by the adrenal cortex and that under conditions of stress it may participate more than cortisone in physiologic reactions. Laboratory studies indicate that hydrocortisone has greater physiologic activity, milligram for milligram, than cortisone and with certain assays its potency is twice as great.Two forms of hydrocortisone, the free alcohol preparation and the acetate, were given systemically to patients with rheumatoid arthritis and were observed to possess significant differences in ability to suppress the disease manifestations. When administered orally in large initial doses, hydrocortisone (free alcohol) appeared to produce greater suppressive effects, milligram for milligram, than either hydrocortisone acetate or cortisone acetate. Comparisons of potency made by determining maintenance dosage requirements for equivalent degrees of clinical control in the same patients indicated that the effectiveness of hydrocortisone (free alcohol) is more than 50 per cent greater than that of either the free or acetated forms of cortisone and approximately twice as great as that of hydrocortisone acetate. Certain observations suggested that the greater antirheumatic activity of hydrocortisone (free alcohol) is not accompanied by a correspondingly greater tendency toward endocrine complications. If more extensive future investigations support this observation, hydrocortisone (free alcohol), by producing equally efficient results with smaller doses, may prove superior to cortisone as a therapeutic agent.Intra-articular injections of hydrocortisone acetate appear to have only a limited place in the management of rheumatoid arthritis but may be used for temporary relief under certain conditions. In preliminary studies by the author it was noted that whereas improvement resulted in 80 per cent of the treated joints, the improvement was graded as pronounced or very pronounced in only one-half of the joints so injected. In almost all instances the benefits derived were quite temporary. Results observed in treatment of osteoarthritic joints by this method were decidedly poorer than in rheumatoid arthritis.

The administration of cortisone acetate to patients with rheumatoid arthritis usually produces prompt and often dramatic suppression of the disease manifestations. The effects of the hormone are not lasting, however, and after withdrawal relapse ensues. For sustained improvement in a chronic disease such as rheumatoid arthritis, it appears that cortisone must be given more or less continuously. This raises the question whether administration may be continued effectively and safely for long periods.Seventy-six patients with rheumatoid arthritis were given cortisone in the hope that treatment could be continued uninterruptedly for extended periods. For various clinical reasons it was necessary to discontinue treatment in 16 of these before six months, but the remaining 60 patients received the hormone uninterruptedly for six to 15 months. By using initial large suppressive amounts, then gradually reducing the dosage, and finally employing smaller maintenance doses, adequate degrees of rheumatic control were maintained in approximately two-thirds of the original 76 patients. The ability to sustain satisfactory improvement varied indirectly, in general, with the severity of the rheumatoid arthritis. The chief detriment to better results in the more severe cases was the intervention of adverse hormonal side effects which developed frequently when large or relatively large maintenance doses were required to support satisfactory improvement. Unwanted signs of hormonal excess developed in 40 per cent of cases at some time during the course of treatment. Most of them were mild or transient and disappeared or lessened when the dose of cortisone was reduced, but when the dose was reduced the degree of improvement often declined also. During prolonged cortisone therapy evidence of functional suppression of the adrenal cortices, as indicated by a decreased response of circulating eosinophils to exogenous ACTH, was present. The depression of cortical function was temporary, however. Whether irreversible damage may result when the drug is employed for longer periods cannot yet be answered.