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Systemic Absorption of Topical Steroids: Metabolic Effects as an Index of Mild Hypercortisolism

Systemic Absorption of Topical Steroids: Metabolic Effects as an Index of Mild Hypercortisolism Abstract • This study was undertaken to determine whether the commonly used treatment of psoriasis with potent topical glucocorticoids results in hypercortisolism and whether metabolic changes might provide a means for monitoring pharmacologic effects of excessive systemic absorption of glucocorticoids. Plasma cortisol, glucose, and insulin and circulating polymorphonuclear leukocytes were assessed under controlled conditions in five otherwise healthy patients with psoriasis (40% to 85% involvement) treated with topical desoximetasone, without occlusion. In all patients, there were rapid and sustained suppression of endogenous cortisol production, twofold to threefold increases in fasting insulin levels indicating insulin resistance, and elevated levels of polymorphonuclear leukocytes. Two patients also experienced reduced glucose tolerance. These findings suggest that application of potent corticosteroids to large areas of diseased skin results in sufficient systemic absorption to cause not only adrenal suppression but some degree of hypercortisolism with greater frequency and rapidity than has been suggested. Prospective monitoring of insulin-glucose relationships as a sensitive index of the metabolic effects of glucocorticoids may provide a means of assessing excess systemic absorption that is not predictable on the basis of adrenal suppression or circulating levels of the drug. Such prediction could have particular relevance in anticipating adverse clinical effects in the treatment of chronic skin disorders with potent topical glucocorticoids. (Arch Dermatol 1986;122:1007-1010) References 1. Scoggins RB, Kliman B: Percutaneous absorption of corticosteroids: Systemic effects . N Engl J Med 1965;273:831-840.Crossref 2. Cornell RC, Stoughton RB: Six-month controlled study of effect of desoximetasone and betamethasone-17-valerate on the pituitary-adrenal axis . Br J Dermatol 1981;105:91-95.Crossref 3. Carruthers JA, August PJ, Staughton RCD: Observations on the systemic effect of topical clobetasol propionate . Br Med J 1975;4:203-204.Crossref 4. Livingood CS, Hildebrand JF, Key JS, et al: Studies on the percutaneous absorption of fludrocortisone . Arch Dermatol 1955;72:313-327.Crossref 5. Fritz KA, Weston WL: Topical glucocorticosteroids . Ann Allergy 1983;50:68-76. 6. Scoggins RB: Decrease of urinary corticosteroids following application of fluocinolone acetonide under an occlusive dressing . J Invest Dermatol 1962;39:473-474.Crossref 7. Queille C, Pommarede R, Saurat J-H: Efficacy vs systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood . Pediatr Dermatol 1984;1:246-253.Crossref 8. Nillson JE, Gip LJ: Systemic effects of local treatment with high doses of potent corticosteroids in psoriatics . Acta Derm Venereol 1979;59:245-248. 9. Kelly A, Nelson K, Goodwin M, et al: Iatrogenic Cushing's syndrome . Br Med J 1972;4:114.Crossref 10. Staughton RCD, August PJ: Cushing's syndrome and pituitary-adrenal suppression due to clobetasol propionate . Br Med J 1975;2:419-421.Crossref 11. May P, Stein EJ, Ryter RJ, et al: Cushing's syndrome from percutaneous absorption of triamcinolone cream . Arch Intern Med 1976;136:612-613.Crossref 12. Himathongkam T, Dasanabhairochana P, Pitchayayothin N, et al: Florid Cushing's syndrome and hirsutism induced by desoximetasone . JAMA 1978;239:430-431.Crossref 13. Cook LJ, Freinkel RK, Zugerman C, et al: Iatrogenic hyperadrenocorticism during topical steroid therapy: Assessment of systemic effects by metabolic criteria . J Am Acad Dermatol 1982;6:1054-1060.Crossref 14. Keipert JA, Kelly R: Temporary Cushing's syndrome from percutaneous absorption of betamethasone-17-valerate . Med J Aust 1971;1:542-544. 15. Burton JL, Cunliffe WJ, Holti G, et al: Complications of topical corticosteroid therapy in patients with liver disease . Br J Dermatol 1974;91( (suppl 10) ):22-23.Crossref 16. Fitzpatrick TB, Griswold HC, Hicks JH: Sodium retention and edema from percutaneous absorption of fludrocortisone acetate . JAMA 1955;158:1149-1152.Crossref 17. Tschan DA, Adoni L: Effect on percutaneous absorption of meticortelone on the eosinophilic count . J Invest Dermatol 1957;28:385-386. 18. Gomez EC, Frost P: Induction of glycosuria and hyperglycemia by topical corticosteroid therapy . Arch Dermatol 1976;112:1559-1562.Crossref 19. Kligman AM, Frosch PJ: Steroid addiction . Int J Dermatol 1979;18:23-31.Crossref 20. Perley M, Kipnis DM: Effect of glucocorticoids on plasma insulin . N Engl J Med 1966;274:1237-1241.Crossref 21. Sharmoon H, Soman V, Sherwin RS: The influence of acute physiological increments of cortisol on fuel metabolism and insulin binding to monocytes in normal humans . J Clin Endocrinol Metab 1980;50:495-501.Crossref 22. Rizza RA, Mandarino LJ, Gerich JE: Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action . J Clin Endocrinol Metab 1982;54:131-138.Crossref 23. Bishop CR, Athens JW, Boggs DR, et al: A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis . J Clin Invest 1968; 47:249-260.Crossref 24. Morgan CR, Lazarow A: Immunoassay of insulin: Two antibody system: Plasma insulin levels of normal, subdiabetic, and diabetic rats . Diabetes 1963;12:115-126. 25. Stoughton RB: Bioassay system for formulations of topically applied glucocorticosteroids . Arch Dermatol 1972;106:825-827.Crossref 26. National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance . Diabetes 1979;28:1039-1057.Crossref 27. Axelrod L: Glucocorticoid therapy . Medicine 1976;55:39-65.Crossref 28. Storrs FJ: Use and abuse of systemic corticosteroid therapy . J Am Acad Dermatol 1979;1:95-105.Crossref 29. Wester RC, Noonan PK, Maibach HI: Frequency of application on percutaneous absorption of hydrocortisone . Arch Dermatol 1977;113:620-622.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Systemic Absorption of Topical Steroids: Metabolic Effects as an Index of Mild Hypercortisolism

Garden, Jerome M.; Freinkel, Ruth K.
Archives of Dermatology , Volume 122 (9) – Sep 1, 1986
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References (31)

Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1986.01660210057018
Publisher site
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Abstract

Abstract • This study was undertaken to determine whether the commonly used treatment of psoriasis with potent topical glucocorticoids results in hypercortisolism and whether metabolic changes might provide a means for monitoring pharmacologic effects of excessive systemic absorption of glucocorticoids. Plasma cortisol, glucose, and insulin and circulating polymorphonuclear leukocytes were assessed under controlled conditions in five otherwise healthy patients with psoriasis (40% to 85% involvement) treated with topical desoximetasone, without occlusion. In all patients, there were rapid and sustained suppression of endogenous cortisol production, twofold to threefold increases in fasting insulin levels indicating insulin resistance, and elevated levels of polymorphonuclear leukocytes. Two patients also experienced reduced glucose tolerance. These findings suggest that application of potent corticosteroids to large areas of diseased skin results in sufficient systemic absorption to cause not only adrenal suppression but some degree of hypercortisolism with greater frequency and rapidity than has been suggested. Prospective monitoring of insulin-glucose relationships as a sensitive index of the metabolic effects of glucocorticoids may provide a means of assessing excess systemic absorption that is not predictable on the basis of adrenal suppression or circulating levels of the drug. Such prediction could have particular relevance in anticipating adverse clinical effects in the treatment of chronic skin disorders with potent topical glucocorticoids. (Arch Dermatol 1986;122:1007-1010) References 1. Scoggins RB, Kliman B: Percutaneous absorption of corticosteroids: Systemic effects . N Engl J Med 1965;273:831-840.Crossref 2. Cornell RC, Stoughton RB: Six-month controlled study of effect of desoximetasone and betamethasone-17-valerate on the pituitary-adrenal axis . Br J Dermatol 1981;105:91-95.Crossref 3. Carruthers JA, August PJ, Staughton RCD: Observations on the systemic effect of topical clobetasol propionate . Br Med J 1975;4:203-204.Crossref 4. Livingood CS, Hildebrand JF, Key JS, et al: Studies on the percutaneous absorption of fludrocortisone . Arch Dermatol 1955;72:313-327.Crossref 5. Fritz KA, Weston WL: Topical glucocorticosteroids . Ann Allergy 1983;50:68-76. 6. Scoggins RB: Decrease of urinary corticosteroids following application of fluocinolone acetonide under an occlusive dressing . J Invest Dermatol 1962;39:473-474.Crossref 7. Queille C, Pommarede R, Saurat J-H: Efficacy vs systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood . Pediatr Dermatol 1984;1:246-253.Crossref 8. Nillson JE, Gip LJ: Systemic effects of local treatment with high doses of potent corticosteroids in psoriatics . Acta Derm Venereol 1979;59:245-248. 9. Kelly A, Nelson K, Goodwin M, et al: Iatrogenic Cushing's syndrome . Br Med J 1972;4:114.Crossref 10. Staughton RCD, August PJ: Cushing's syndrome and pituitary-adrenal suppression due to clobetasol propionate . Br Med J 1975;2:419-421.Crossref 11. May P, Stein EJ, Ryter RJ, et al: Cushing's syndrome from percutaneous absorption of triamcinolone cream . Arch Intern Med 1976;136:612-613.Crossref 12. Himathongkam T, Dasanabhairochana P, Pitchayayothin N, et al: Florid Cushing's syndrome and hirsutism induced by desoximetasone . JAMA 1978;239:430-431.Crossref 13. Cook LJ, Freinkel RK, Zugerman C, et al: Iatrogenic hyperadrenocorticism during topical steroid therapy: Assessment of systemic effects by metabolic criteria . J Am Acad Dermatol 1982;6:1054-1060.Crossref 14. Keipert JA, Kelly R: Temporary Cushing's syndrome from percutaneous absorption of betamethasone-17-valerate . Med J Aust 1971;1:542-544. 15. Burton JL, Cunliffe WJ, Holti G, et al: Complications of topical corticosteroid therapy in patients with liver disease . Br J Dermatol 1974;91( (suppl 10) ):22-23.Crossref 16. Fitzpatrick TB, Griswold HC, Hicks JH: Sodium retention and edema from percutaneous absorption of fludrocortisone acetate . JAMA 1955;158:1149-1152.Crossref 17. Tschan DA, Adoni L: Effect on percutaneous absorption of meticortelone on the eosinophilic count . J Invest Dermatol 1957;28:385-386. 18. Gomez EC, Frost P: Induction of glycosuria and hyperglycemia by topical corticosteroid therapy . Arch Dermatol 1976;112:1559-1562.Crossref 19. Kligman AM, Frosch PJ: Steroid addiction . Int J Dermatol 1979;18:23-31.Crossref 20. Perley M, Kipnis DM: Effect of glucocorticoids on plasma insulin . N Engl J Med 1966;274:1237-1241.Crossref 21. Sharmoon H, Soman V, Sherwin RS: The influence of acute physiological increments of cortisol on fuel metabolism and insulin binding to monocytes in normal humans . J Clin Endocrinol Metab 1980;50:495-501.Crossref 22. Rizza RA, Mandarino LJ, Gerich JE: Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action . J Clin Endocrinol Metab 1982;54:131-138.Crossref 23. Bishop CR, Athens JW, Boggs DR, et al: A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis . J Clin Invest 1968; 47:249-260.Crossref 24. Morgan CR, Lazarow A: Immunoassay of insulin: Two antibody system: Plasma insulin levels of normal, subdiabetic, and diabetic rats . Diabetes 1963;12:115-126. 25. Stoughton RB: Bioassay system for formulations of topically applied glucocorticosteroids . Arch Dermatol 1972;106:825-827.Crossref 26. National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance . Diabetes 1979;28:1039-1057.Crossref 27. Axelrod L: Glucocorticoid therapy . Medicine 1976;55:39-65.Crossref 28. Storrs FJ: Use and abuse of systemic corticosteroid therapy . J Am Acad Dermatol 1979;1:95-105.Crossref 29. Wester RC, Noonan PK, Maibach HI: Frequency of application on percutaneous absorption of hydrocortisone . Arch Dermatol 1977;113:620-622.Crossref

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Archives of Dermatology – American Medical Association

Published: Sep 1, 1986

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