Don H. Nelson

SOME QUANTITATIVE FACTORS IN TOPICAL CORTICOSTEROID THERAPY.

Corticosteroids are presently the most widely used and effective agents in topical therapy of cutaneous disease. The use of plastic film dressings increases the effectiveness of treatment, but also increases absorption and the possibility of systemic corticosteroid effects, and raises the question of possible adverse effects on pituitary‐adrenal function. A summary of previously published studies on this question is presented, and criteria for distinguishing transient adrenal suppression from true adrenal insufficiency are outlined. Proved cases of adrenal insuffiCiency caused by topical corticosteroids have not been reported, but the number of properly studied cases is too small for firm conclusions. The question of “dosage” of topically applied corticosteroids has heretofore received scant attention. A dosage schedule, which is effective treatment for many steroid responsive lesions and is below the range which produces significant systemic effects, is presented. The results of pituitary‐adrenal function tests in specific cases treated with known amounts of topical corticosteroids are presented. Because of the importance and widespread use of topical corticosteroids, it is urged that further study of these questions be pursued.

Cushing's syndrome—Pituitary or adrenal origin?

Abstract It seems probable that the etiology of Cushings syndrome can be conveniently divided into at least two categories and perhaps more. First, there are patients who have a condition limited to the adrenal gland, such as the benign adenomas and carcinomas, which generally do not appear to be dependent upon pituitary ACTH production. There is no primary defect in pituitary secretion in these patients and the reason for the adrenal disturbance is unknown. Second, there is a group of patients in whom tumors of the pituitary gland are associated with Cushings syndrome. In most of these the direct determination of increased levels of plasma ACTH has not been carried out, but the connection seems probable and is strengthened by the recent demonstration of elevated plasma ACTH in a few of these patients. Third, there is a group of patients who may or may not fall into the group with primary pituitary disease. These are patients who have hyperplasia of both adrenal cortices in whom there is fairly good evidence that there is increased production of ACTH producing adrenal hypertrophy, but in whom there has been no demonstration of clear-cut pituitary pathology. The fact that one can suppress adrenal function in these patients, if sufficient corticosteroid is administered, suggests that normal pituitary controls are not abolished, but seems to indicate that the “thermostat” has been set up in such a way that the anterior pituitary secretes ACTH to produce a higher than normal level of corticosteroid production. It is possible that the pathology of Cushings syndrome is in neither the adrenal nor the pituitary gland in cases with bilateral hyperplasia. A “relative deficiency” in other tissues might result in a stimulus to increase ACTH just as it does in conditions of stress. Thus it has been demonstrated that following trauma to dogs, plasma levels of ACTH and of corticosteroids may be simultaneously elevated. 12 It is not possible at this time to state definitely whether pituitary tumors, which occur following bilateral adrenalectomy for Cushings syndrome, occur as the result of continued growth of small tumors or may possibly be the result of a stimulus of peripheral origin which acts to stimulate ACTH secretion. A combination of such a stimulus to the formation of Cushings syndrome and removal of both adrenal glands with resultant fall in plasma corticosteroid levels may act as a powerful stimulus to ACTH secretion and be followed by tumor formation in the anterior pituitary gland. Further knowledge will have to be obtained along a number of lines of investigation before we have a clear understanding of the factors which produce Cushings syndrome. Specifically, a better understanding must be obtained of the relationships between the pituitary production of ACTH and the stimulus to this production, and better means must be developed for the determination of ACTH in blood.