[Skip to Content]
[Skip to Content Landing]
Article
June 1960

Therapeutic Doses of Salicylates: Effect on Adrenal Cortical Secretory Activity in Normal Subjects

Author Affiliations

Birmingham, Ala.

From the Department of Medicine and University Hospital, University of Alabama Medical Center and the Medical Service, Veterans Administration Hospital, Birmingham, Ala.; Trainee of the National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health, United States Public Health Service (Dr. Ulloa).

AMA Arch Intern Med. 1960;105(6):914-920. doi:10.1001/archinte.1960.00270180092012
Abstract

Introduction  Similarities between the anti-inflammatory effects obtained from salicylate and glucocorticoid therapy in rheumatic diseases have led to speculation as to a common mode of action of these two substances. Metabolic studies using current laboratory procedures have, however, often produced conflicting results. Data have been reported supporting the concept that salicylates stimulate the pituitary-adrenal axis in man. In other studies these data have not been confirmed and, indeed, appear to have been contradicted. Some investigators have reported an increase in the urinary reducing steroids and no change in neutral 17-ketosteroids after salicylate therapy.1-3 Others have reported a significant decrease in the urinary 17-hydroxycorticosteroid excretion with a slight decrease in 17-ketosteroid excretion in individuals who have been given large doses of salicylates.4 Other reports have shown no significant alteration in either urinary 17-ketosteroids 5-7 or 17-hydroxycorticosteroids 6,7 following salicylate administration.In many of the earlier studies in man, massive

References
1.
Acetylsalicylic acid.
2.
van Cauwenberge, H., and Heusghem, C.:  Acetylsalicylic Acid and Urinary Excretion of Adrenocortical Steroids ,  Lancet 1:771, 1951.Crossref
3.
Roskam, J., and van Cauwenberge, H.:  Cortisone, ACTH et salicylés dans le traitement des rhumatismes inflamatoires et des états similaires ,  Presse méd. 60:1344, 1952.
4.
Roskam, J., and van Cauwenberge, H.:  Salicylate de soude, aspirine et corticoides reducteurs dans le traitement de la maladie de Bouilland ,  Semaine hôp. Paris 28:1158, 1942.
5.
Done, A. K. Ely, R. S., and Kelley, V. C.:  Response of Plasma 17-Hydroxycorticosteroids to Salicylate Administration in Normal Human Subjects ,  Metabolism 4:129, 1955.
6.
Cochran, J. B.; Watson, R. D., and Reid, J.:  Mild Cushing's Syndrome Due to Aspirin ,  Brit. M.J. 2:1411, 1950.Crossref
7.
Henley, A. A.:  Steroid Metabolism in Rheumatoid Arthritis ,  Ann. Rep. West London Hosp. 1952, pp. 24-26.
8.
Eades, C. H., Jr., and King, J. S., Jr.:  The Action of Salicylate as Related to Pituitary-Adrenal Function ,  Internat. Rec. Med. 169:646, 1956.
9.
Peterson, R. E.; Black, R. L., and Bunim, J. J.:  Salicylates and Adrenocortical Function in Man ,  Arthritis & Rheumat. 1:29, 1958.
10.
Drekter, I. J.; Heisler, A.; Scism, G. R.; Stern, S.; Pearson, S., and McGavack, T. H.:  The Determination of Urinary Steroids: I. The Preparation of Pigment-Free Extracts and a Simplified Procedure for the Estimation of Total 17-Ketosteroids ,  J. Clin. Endocrinol. 12:55, 1952.
11.
Holtorff, A. F., and Koch, F. C.:  The Colorimetric Estimation of 17-Ketosteroids and Their Application to Urine Extracts ,  J. Biol. Chem. 135:377, 1940.
12.
Reddy, W. J.:  Modification of the Reddy-Jenkins-Thorn Method for Estimation of 17-Hydroxycorticoids in Urine ,  Metabolism 3:489, 1954.
13.
Clark, L. C., Jr., and Thompson, H. L.:  Determination of Creatine and Creatinine in Urine ,  Analyt. Chem. 21:1218, 1949.
14.
Varley, H.:  Practical Clinical Biochemistry , New York, Interscience Publishers, 1954, pp. 498-500.
15.
van Cauwenberge, H.:  Relation of Salicylate Action to Pituitary Gland: Observations in Rats ,  Lancet 2:374, 1951.
16.
Blanchard, K. C.; Dearborn, E. H.; Maren, T. H., and Marshall, E. K., Jr.:  Stimulation of the Anterior Pituitary by Certain Cinchoninic Acid Derivatives ,  Bull. Johns Hopkins Hosp. 86:83, 1950.
17.
Cronheim, G.; King, J. S., Jr., and Hyder, N.:  Effect of Salicylic Acid and Similar Compounds on Adrenal-Pituitary System ,  Proc. Soc. Exper. Biol. & Med. 80:51, 1952.
18.
Hetzel, B. S., and Hine, D. D.:  Effect of Salicylates on Pituitary and Suprarenal Glands ,  Lancet 2:94, 1951.
19.
Barnett, G. O., and Teague, R. S.:  The Antagonism of Salicylate to Diethylstilbestrol upon Liver Glycogen in the Rat ,  Endocrinology 63:205, 1958.
20.
van Cauwenberge, H.:  Réactivité cortioosurrénalienne et dosage des corticostéroides sanguins chez le rat ,  Compt. rend. soc. biol. 150:1828, 1956.
21.
Bertolani, F.; Lorenzini, R., and Bonati, B.:  Salicylates in Acute Osteomyelitis ,  Lancet 1:54, 1951.
22.
Done, A. K.; Ely, R. S., and Kelley, V. C.:  Influence on Circulating 17-Hydroxycorticosteroid Concentrations of Compounds Structurally Related to Salicylate ,  Proc. Soc. Exper. Biol. & Med. 93: 294, 1956.
23.
Good, T. A.; Done, A. K.; Ely, R. S., and Kelley, V. C.:  Effects of Salicylate on Plasma 17-Hydroxycorticosteroids in Hypophysectomized and Adrenalectomized Guinea Pigs ,  Metabolism 6: 346, 1957.
24.
Roskam, J.; van Cauwenberge, H., and Mutsers, A.:  Effect of Sodium Salicylates on Circulating Eosinophils and Urinary Uric-Acid: Creatinine Ratio in Healthy Volunteers ,  Lancet 2:375, 1951.Crossref
25.
Kelemen, E.; Majoros, M.; Ivanyi, J., and Kovacs, K.:  Salicylates, Stress and Cortisone ,  Experientia 6:435, 1950.Crossref
26.
Pasqualini, R. Q., and Luscalea, M. C.:  Tratamiento de la fiebre reumatica con salicilato de sodio y cloruro de amonio ,  Prensa méd. argent. 35:1091, 1948.
27.
Marson, F. G. W.:  Effect of ACTH and Sodium Salicylate on the Urinary Uric Acid: Creatinine Ratio, and Circulating Eosinophils in Man ,  Ann. Rheumat. Dis. 12:296, 1953.Crossref
28.
Meade, B. W., and Smith, M. J. H.:  Salicylate, Gentisate, and Circulating Eosinophils ,  Lancet 1:773, 1951.Crossref
29.
Boe, J., and Stoa, K. F.:  ACTH-like Effect of Acetylsalicylic Acid, Investigation of Combined Treatment with Acetylsalicylic Acid and Panthotenic Acid ,  Acta endocrinol. 12:201, 1953.
30.
Coste, F.; Bourel, M.; Delbarre, F., and Weissenbach, R.:  Comment agit le salicylate de sodium?  Presse méd. 61:979, 1953.
31.
Ely, R. S.; Ainger, L. E.; Seely, J. R.; Done, A. K., and Kelley, V. C.:  Studies of 17-Hydroxycorticosteroids: X. Urinary Excretion of 17-Hydroxycorticosteroids in Patients with Rheumatic Fever ,  J. Clin. Endocrinol. 15:523, 1955.Crossref
32.
Done, A. K.; Ely, R. S., and Kelley, V. C.:  Studies of 17-Hydroxycorticosteroids: Blood Levels in Salicylate Intoxication ,  J. Pediat. 44:153, 1954.Crossref
33.
Roskam, J.; van Cauwenberge, H.; Vivario, R., and Vliers, M.:  Les Modes d'action de la salicylothérapie ,  Presse méd. 63:1105, 1955
34.
Bayliss, R. I. S., and Steinbeck, A. W.:  Salicylates and the Plasma Level of Adrenal Steroids ,  Lancet 1:1010, 1954.Crossref
35.
Seely, J. R.; Ely, R. S.; Done, A. K.; Ainger, L. F., and Kelley, V. C.:  Studies of 17-Hydroxycorticosteroids: VII. Effects of Therapy on Concentration of 17-Hydroxycorticosteroids in the Plasma of Patients with Rheumatic Fever ,  Pediatrics 15:543, 1955.
36.
Ward, L. E.; Wu, C.; Hench, P. S.; Slocumb, C. H.; Polley, H. F., and Mayne, J. G.:  Plasma 17-Hydroxycorticosteroids in Patients with Certain Rheumatic Diseases and in Normal Persons ,  Proc. Staff Meet. Mayo Clin. 33:611, 1958.
37.
Smith, M. J. H.; Gray, C. H., and Lunnon, J. B.:  Urinary Excretion of Adrenocortical Steroids by Patients Receiving Salicylates ,  Lancet 1:1008, 1954.Crossref
38.
Herndon, R. F.; Freeman, S.; Wheeler, J., and Lestina, F. A.:  The Acute Effect of Acetylsalicylic Acid in Man: On the Plasma Concentration of Corticoids, the Corticotropin (ACTH) Response, and Urinary Steroid Excretion ,  A.M.A. Arch. Int. Med. 101:623, 1958.Crossref
39.
Ungar, G.; Damgaard, E., and Hummel, F. P.:  Action of Salicylates and Related Drugs on Inflammation ,  Am. J. Physiol. 171:545, 1952.
×