592

INDUSTRIAL

HYGIENE

AND

OCCUPATIONAL

MEDICINE

In patients with interval gout or a uric acid diathesis severe acute attacks may
appear for the first time following the withdrawal of AGTH and cortisone. This
may be treated by either reinstituting ACTH and cortisone treatment for an
additional 24-48 hours together with colchicine or using colchicine alone.
Hormonal Changes.—Functional Depression of the Pituitary-Adrenocortical
Axis: Evidence has been obtained from several sources that following the with­
drawal of cortisone there is a temporary functional depression of the adrenal cortex.3 * * * * *
It is characterized by asthenia and lassitude. The presence of adrenal insufficiency
may be shown by a failure of the adrenal cortex to respond to ACTH stimulation.
This unresponsiveness usually lasts four to seven days, but on occasion in patients
who have had prolonged courses of cortisone therapy the adrenal cortical depression
may last as long as 10 to 14 days (table 3). If the development of adrenal cortical
insufficiency is acute, it may prove fatal. Therefore, it is important with cortisone
or with other types of adrenal steroid therapy, such as 17-hydroxycorticosterone
(compound F), to reduce the dose gradually and slowly increase the interval between
doses before the complete cessation of treatment. It may also be prevented by
administering ACTH during the withdrawal of cortisone. This allows the depresTable

3.—Adrenal Cortical Depression During Cortisone Treatment in a Woman Aged
35 with Hyperthyroidism

Treatment
0
Cortisone, 100 me. X 10 days..................................................'.
Cortisone, 200 me. X 6 days......................................................
0X6 days
ACTH, 40 mg. X 2 days...............................................................

17-Ketosteroids
(Mg./24 Hr.)*

4-Hr. AOTH Test
Fall in Eosinophils,
Per Cent

8.8
4.6
7.6

—96%
.........
.........

7.6

— 7%

* Cortisone therapy has caused a reduction in 17-ketosteroids excretion. This suppression of adrenal
cortical activity is aiso shown by the failure of ACTH to cause a rise in 17-ketosteroids or a significant fall
in circulating eosinophils.
'

sion of the anterior pituitary adrenocorticotropic mechanism to disappear gradually
and leads to increasing amounts of endogenous corticotropin production, stimula­
tion of the patient’s adrenal cortices and eventually restoration of the pituitary
adrenocortical system to normal.
Following the administration of ACTH there is also functional depression of
the adrenal cortex, and temporary adrenal insufficiency develops. It is due to
suppression of endogenous pituitary production of corticotropin, is less prolonged
and less complete than that following cortisone, since the adrenal itself remains
enlarged, capable of active secretion and in a state of ready responsiveness. _to stimu­
lation. The development of adrenal cortical insufficiency is readily prevented if the
ACTH is gradually reduced before it is discontinued. Epinephrine has been sug­
gested as a possible means of stimulating the functionally depressed pituitary but
has not proved effective in this regard.
3. Sprague, R. G.; Power,. M. H.; Mason, H. R.; Albert, A.; Mathieson, D. B. ;.JHench,
P. S.; Kendall, E. C.; Slocumb, C. H., and Polley, H. F.: Observations on the Physiological
Effects of Cortisone and ACTH in Man, Arch. Int. Med. 85:199-258 (Feb.) 1950. Forsham,
P. H.; Thorn, G. W.; Frawley, T. F., and Wilson, D. L.: Studies on the Functional State of
the Adrenal Cortex During and Following ACTH and Cortisone Therapy, J. Clin. Invest.
29:812, 1950. Thorn and others.10