FRAWLEY—COMPLICATIONS

OF ACTH

AND. CORTISONE

THERAPY

589

that the improvement or lack of improvement in diseases treated with ACTH or
cortisone can be attributed to metabolic or electrolytic changes. Nevertheless,
although these effects are relatively unimportant in terms of therapeutic responsive­
ness, they may be of major importance when they appear during treatment with
ACTH, cortisone or similar steroids. With a full understanding of the physio­
logical actions which result from an insufficiency or an excess of circulating corticoids, the management of patients during ACTH and cortisone treatment will
become less of a problem.
UNTOWARD PHYSIOLOGICAL EFFECTS

In this discussion the term “untoward effects” refers to physiological alterations
which accompany ACTH and cortisone administration but which at present appear
to be of no therapeutic benefit. Occasionally the early preparations of ACTH, due
to posterior pituitary contamination, caused blanching of the skin and abdominal
cramps, but with the improved preparations of ACTH now available these reactions,
as well as antigenic reactions to ACTH, are now so rare that ACTH may be safely
administered intravenously.2 The intramuscular administration of cortisone may
rarely cause local irritation, erythema and skin rashes. These are probably due to
the vehicle in the preparation used rather than to the cortisone molecule per se.
The untoward physiological effects associated with the administration of ACTH
and cortisone may be conveniently considered under the following headings.
Alterations in Electrolyte Metabolism.—One of the characteristic chemical blood
findings which has been observed in hyperadrenocorticism, and from ACTH or
cortisone, is hypopotassemic, hypochloremic alkalosis. This is noted particularly
when the dosage is high and the course of therapy prolonged. One of the character­
istic physiological actions of the majority of adrenal steroids is to increase potassium
excretion, and the changes in serum chloride and serum pH follow. The presence
of this abnormal serum electrolyte pattern, particularly hypopotassemia, is suggested
clinically by the development of lethargy, muscular weakness and cardiac irregu­
larities. Early chemical evidence consists of a lowered serum chloride and an
elevated carbon dioxide-combining power. If the level of serum chloride and the
C02 combining power are significantly altered in this way, it is likely that the serum
potassium is. low. The latter produces characteristic changes in the electrocardio­
gram (chart 1), which thus becomes a useful substitute for chemical determinations
of serum potassium concentration.
In order to prevent hypopotassemia, hypochloremic alkalosis, potassium chloride
should be administered, i Not only does it supply the required potassium and
chloride ions but, in addition, its' diuretic action reduces water retention, which gen­
erally accompanies adrenal hormone treatment. The usual dosage is 0.9 Gm. three
times a day as enteric-coated tablets. This will suffice in most cases. With an
occasional patient it will be necessary to increase the potassium chloride to a total
daily dose of 5.4 Gm. It appears that the amount of potassium required in some
patients is related to the level of;adrenal cortical hormone attained from ACTH
stimulation or cortisone treatmeint. The greater the elevation of the hormone levels
the greater the possibility of. hypopotassemia.N While hypopotassemia calls for
prompt treatment, it should be pointed out that .overzealous administration of
2. Renold, A. E.; Forsham, P. H.; Maisterrena, J., and Thorn, G. W.: Intravenous ACTH
(Preliminary Report), New England J. Med. 244:796-798, 1951.