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Decrease of Ocular Pressure With Oral Metyrapone: A Double-Masked Crossover Trial

Decrease of Ocular Pressure With Oral Metyrapone: A Double-Masked Crossover Trial Abstract • To examine the effect of a decrease in plasma cortisol level on intraocular pressure, 14 subjects with elevated ocular pressure were given oral metyrapone tartrate (an inhibitor of adrenal cortisol biosynthesis) and a placebo in a doublemasked, two-period, crossover trial. Ocular pressure and the adrenal response were monitored over a seven-hour period. The decrease in ocular pressure after metyrapone administration was significantly greater than that after placebo. The 14 subjects could be designated as responders or nonresponders by decline of ocular pressure after metyrapone administration compared with response after placebo. The responders could be further differentiated from the nonresponders by a smaller decrease in ocular pressure over time in response to the placebo and by a smaller decrease over time of plasma cortisol level in response to metyrapone. These results provide further evidence that plasma glucocorticoids may play a role in the regulation of ocular pressure. References 1. Bernstein HN, Schwartz B: Effects of longterm systemic steroids on ocular pressure and tonographic values . Arch Ophthalmol 1962;68:742-752.Crossref 2. Armaly MF: Effects of corticosteroids on intraocular pressure and fluid dynamics . Arch Ophthalmol 1963;70:482-499.Crossref 3. Becker B, Hahn KA: Topical corticosteroids and heredity in primary open angle glaucoma . Am J Ophthalmol 1964;57:543-550. 4. Kimura R, Maekawa N: Effect of orally administered hydrocortisone on the ocular tension in primary open angle glaucoma subjects . Acta Ophthalmol 1976;54:430-436.Crossref 5. Weinreb RN, Polansky JR, Kramer SC, et al: Acute effects dexamethasone on intraocular pressure in glaucoma . Invest Ophthalmol Vis Sci 1985;26:170-175. 6. Neuner HP, Bayer JM: Das Vorhalten des Augeninnendruckes sowie des Brachialis- und des Ophthalmica-blutdruckes beim Cushing-Syndrom vor und nach operativen Eingriffen an den Nebennieren: Ein statistischer Vergleich . Doc Ophthalmol 1969;27:221-231.Crossref 7. Sayegh F, Weigelin F: Intraocular pressure in Cushing's syndrome . Ophthalmic Res 1975;7:390-394.Crossref 8. Horie T, Kitazawa Y: The clinical significance of diurnal pressure variation in primary open angle glaucoma . Jpn J Ophthalmol 1979;23:310-333. 9. Boyd TAS, McLeod LE, Hassard DTR, et al: Relation of diurnal variation of plasma corticoid levels and intraocular pressure in glaucoma . Can Med Assoc J 1962;86:772-775. 10. Boyd TAS, McLeod LE: Circadian rhythms of plasma corticoid levels, intraocular pressure and aqueous outflow facility in normal and glaucomatous eyes . Ann NY Acad Sci 1964;117:597-611.Crossref 11. Schwartz B: Physiological effects of steroids . Int Ophthalmol Clin 1966;6:763-765. 12. Weitzman ED, Henkind P, Leitman M, et al: Correlative 24-hour relationships between intraocular pressure and plasma cortisol in normal subjects and patients with glaucoma . Br J Ophthalmol 1975;59:566-572.Crossref 13. Schwartz B, Seddon JM: Increased plasma cortisol levels in ocular hypertension . Arch Ophthalmol 1981;99:1791-1794.Crossref 14. Schwartz B, Levene RZ: Plasma cortisol differences between normal and glaucomatous patients . Arch Ophthalmol 1972;87:369-377.Crossref 15. Starka L, Obenberger J: Steroids and intraocular pressure . J Steroid Biochem 1976;7:979-983.Crossref 16. Weinstein BI, Altman K, Gordon GG, et al: Specific glucocorticoid receptor in the iris-ciliary body of the rabbit . Invest Ophthalmol Vis Sci 1977;16:973-976. 17. McCarty GR, Schwartz B: Increased concentration of glucocorticoid receptors in rabbit iris-ciliary body compared to rabbit liver . Invest Ophthalmol Vis Sci 1982;23:525-527. 18. Weinreb RN, Bloom E, Baxter JD, et al: Detection of glucocorticoid receptors in cultured human trabecular meshwork . Invest Ophthalmol Vis Sci 1981;22:403-407. 19. Hernandez MR, Wenk EJ, Weinstein BI, et al: Glucocorticoid target cells in human outflow pathway: Autopsy and surgical specimens . Invest Ophthalmol Vis Sci 1983;24:1612-1616. 20. Sonino N: Inhibition of adrenal steroid biosynthesis by metyrapone , in Agarwal MK (ed): Hormone Antagonists . Berlin, Walter de Gruyter & Co, 1982, pp 420-429. 21. Schwartz B: Cupping and pallor of the optic disc . Arch Ophthalmol 1973;89:272-277.Crossref 22. Dickstein G, Barsilai D: Improved single dose metyrapone test . Isr J Med Sci 1980;16:365-369. 23. Jubiz W, Meikle AW, West CD, et al: Single dose metyrapone test . Arch Intern Med 1970;125:472-474.Crossref 24. Endocrine Sciences: Plasma Cortisol Radiommunoassay Procedure, Antiserum No. 21-53 . Tarzana, Calif, Endocrine Sciences, 1972. 25. Jaffe BM: Glucocorticoids: Cortisol, corticosterone and compound S , in Jaffe BM, Behrman HR (eds): Methods of Hormone Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, pp 395-415. 26. Jaffe BM: Adrenocorticotropic hormone and melanocyte stimulating hormone , in Jaffe BM, Behrman HR (eds): Methods of Hormone Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, pp 125-159. 27. Amersham-Searle ACTH RIA Kit . Arlington Heights, Ill, Amersham Corp, 1976. 28. Meikle AW, Jubiz W, West CD: A simple fluorometric method for assay of plasma metyrapone . J Lab Clin Med 1969;74:515-520. 29. Colton T: Statistics in Medicine . Boston, Little Brown & Co Inc, 1974. 30. Grizzle JE: The two period change-over design and its use in clinical trials . Biometrics 1965;21:467-480.Crossref 31. Wallenstein S, Fisher AC: The analysis of the two-period repeated measurements crossover design with application to clinical trials . Biometrics 1977;33:261-269.Crossref 32. Brown BW Jr: The crossover experiment for clinical trials . Biometrics 1980;36:69-70.Crossref 33. Louis TA, Lavori PW, Bailer JC III, et al: Crossover and self-controlled designs in clinical research . N Engl J Med 1984;310:24-31.Crossref 34. Jubiz W, Matzukura S, Meikle AW, et al: Plasma metyrapone adrenocorticotropic hormone, cortisol and deoxycortisol levels . Arch Intern Med 1970;125:468-474.Crossref 35. Best JD, Alford FP, Donald RA: Evaluation of the three hour metyrapone test in adults . Clin Endocrinol 1980;13:69-76.Crossref 36. Sprunt JG, Browing MCK, Hannah DM: Some aspects of the pharmacology of metyrapone . Proc R Soc Med 1967;60:908-909. 37. Spiger M, Jubiz W, Meikle AW, et al: Single dose metyrapone test: Review of a four-year experience . Arch Intern Med 1975;135:698-700.Crossref 38. Southren AL, Gordon GG, Munnangi PR, et al: Altered cortisol metabolism in cells cultured from trabecular meshwork specimens obtained from patients with primary open angle glaucoma . Invest Ophthalmol Vis Sci 1983;24:1413-1417. 39. Weinstein BI, Munnangi P, Gordon GG, et al: Defects in cortisol-metabolizing enzymes in primary open angle glaucoma . Invest Ophthalmol Vis Sci 1985;26:890-893. 40. Schoneshofer M, Fenner A: Alteration of plasma levels of pituitary hormones after oral application of metyrapone . Horm Metab Res 1981;13:473-474.Crossref 41. Starka L, Hampl R, Gregorova I, et al: Aldosterone: Its occurrence, metabolism and binding in the rabbit eye . Exp Eye Res 1977;25:91-98.Crossref 42. Frenkel M, Krill AE: Effects of two mineralocorticoids and ocular tension . Arch Ophthalmol 1964;72:315-318.Crossref 43. Cole DF: Reduction in aqueous humor formation as caused by iodate, spironolactone and polyphloretin phosphate . Br J Ophthalmol 1962;46:291.Crossref 44. Starka L, Obenberger J, Louzensky G: Effect of aldactone administration into the rabbit eye . Ophthalmic Res 1981;13:160-164.Crossref 45. Waitzman MB: Aldosterone and aqueous humor dynamics . Acta Ophthalmol 1963;41:111-118.Crossref 46. Schwartz DE: The effect of spironolactone and triamterene on intraocular pressure: A negative report . Ann Ophthalmol 1974;6:105-108. 47. Schwartz B, Golden MA, Wiznia RA, et al: Differences of adrenal stress control mechanisms in subjects with glaucoma and normal subjects . Arch Ophthalmol 1981;99:1770-1777.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Decrease of Ocular Pressure With Oral Metyrapone: A Double-Masked Crossover Trial

Archives of Ophthalmology , Volume 105 (6) – Jun 1, 1987

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American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0003-9950
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1538-3687
DOI
10.1001/archopht.1987.01060060063034
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Abstract

Abstract • To examine the effect of a decrease in plasma cortisol level on intraocular pressure, 14 subjects with elevated ocular pressure were given oral metyrapone tartrate (an inhibitor of adrenal cortisol biosynthesis) and a placebo in a doublemasked, two-period, crossover trial. Ocular pressure and the adrenal response were monitored over a seven-hour period. The decrease in ocular pressure after metyrapone administration was significantly greater than that after placebo. The 14 subjects could be designated as responders or nonresponders by decline of ocular pressure after metyrapone administration compared with response after placebo. The responders could be further differentiated from the nonresponders by a smaller decrease in ocular pressure over time in response to the placebo and by a smaller decrease over time of plasma cortisol level in response to metyrapone. These results provide further evidence that plasma glucocorticoids may play a role in the regulation of ocular pressure. References 1. Bernstein HN, Schwartz B: Effects of longterm systemic steroids on ocular pressure and tonographic values . Arch Ophthalmol 1962;68:742-752.Crossref 2. Armaly MF: Effects of corticosteroids on intraocular pressure and fluid dynamics . Arch Ophthalmol 1963;70:482-499.Crossref 3. Becker B, Hahn KA: Topical corticosteroids and heredity in primary open angle glaucoma . Am J Ophthalmol 1964;57:543-550. 4. Kimura R, Maekawa N: Effect of orally administered hydrocortisone on the ocular tension in primary open angle glaucoma subjects . Acta Ophthalmol 1976;54:430-436.Crossref 5. Weinreb RN, Polansky JR, Kramer SC, et al: Acute effects dexamethasone on intraocular pressure in glaucoma . Invest Ophthalmol Vis Sci 1985;26:170-175. 6. Neuner HP, Bayer JM: Das Vorhalten des Augeninnendruckes sowie des Brachialis- und des Ophthalmica-blutdruckes beim Cushing-Syndrom vor und nach operativen Eingriffen an den Nebennieren: Ein statistischer Vergleich . Doc Ophthalmol 1969;27:221-231.Crossref 7. Sayegh F, Weigelin F: Intraocular pressure in Cushing's syndrome . Ophthalmic Res 1975;7:390-394.Crossref 8. Horie T, Kitazawa Y: The clinical significance of diurnal pressure variation in primary open angle glaucoma . Jpn J Ophthalmol 1979;23:310-333. 9. Boyd TAS, McLeod LE, Hassard DTR, et al: Relation of diurnal variation of plasma corticoid levels and intraocular pressure in glaucoma . Can Med Assoc J 1962;86:772-775. 10. Boyd TAS, McLeod LE: Circadian rhythms of plasma corticoid levels, intraocular pressure and aqueous outflow facility in normal and glaucomatous eyes . Ann NY Acad Sci 1964;117:597-611.Crossref 11. Schwartz B: Physiological effects of steroids . Int Ophthalmol Clin 1966;6:763-765. 12. Weitzman ED, Henkind P, Leitman M, et al: Correlative 24-hour relationships between intraocular pressure and plasma cortisol in normal subjects and patients with glaucoma . Br J Ophthalmol 1975;59:566-572.Crossref 13. Schwartz B, Seddon JM: Increased plasma cortisol levels in ocular hypertension . Arch Ophthalmol 1981;99:1791-1794.Crossref 14. Schwartz B, Levene RZ: Plasma cortisol differences between normal and glaucomatous patients . Arch Ophthalmol 1972;87:369-377.Crossref 15. Starka L, Obenberger J: Steroids and intraocular pressure . J Steroid Biochem 1976;7:979-983.Crossref 16. Weinstein BI, Altman K, Gordon GG, et al: Specific glucocorticoid receptor in the iris-ciliary body of the rabbit . Invest Ophthalmol Vis Sci 1977;16:973-976. 17. McCarty GR, Schwartz B: Increased concentration of glucocorticoid receptors in rabbit iris-ciliary body compared to rabbit liver . Invest Ophthalmol Vis Sci 1982;23:525-527. 18. Weinreb RN, Bloom E, Baxter JD, et al: Detection of glucocorticoid receptors in cultured human trabecular meshwork . Invest Ophthalmol Vis Sci 1981;22:403-407. 19. Hernandez MR, Wenk EJ, Weinstein BI, et al: Glucocorticoid target cells in human outflow pathway: Autopsy and surgical specimens . Invest Ophthalmol Vis Sci 1983;24:1612-1616. 20. Sonino N: Inhibition of adrenal steroid biosynthesis by metyrapone , in Agarwal MK (ed): Hormone Antagonists . Berlin, Walter de Gruyter & Co, 1982, pp 420-429. 21. Schwartz B: Cupping and pallor of the optic disc . Arch Ophthalmol 1973;89:272-277.Crossref 22. Dickstein G, Barsilai D: Improved single dose metyrapone test . Isr J Med Sci 1980;16:365-369. 23. Jubiz W, Meikle AW, West CD, et al: Single dose metyrapone test . Arch Intern Med 1970;125:472-474.Crossref 24. Endocrine Sciences: Plasma Cortisol Radiommunoassay Procedure, Antiserum No. 21-53 . Tarzana, Calif, Endocrine Sciences, 1972. 25. Jaffe BM: Glucocorticoids: Cortisol, corticosterone and compound S , in Jaffe BM, Behrman HR (eds): Methods of Hormone Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, pp 395-415. 26. Jaffe BM: Adrenocorticotropic hormone and melanocyte stimulating hormone , in Jaffe BM, Behrman HR (eds): Methods of Hormone Radioimmunoassay . Orlando, Fla, Academic Press Inc, 1974, pp 125-159. 27. Amersham-Searle ACTH RIA Kit . Arlington Heights, Ill, Amersham Corp, 1976. 28. Meikle AW, Jubiz W, West CD: A simple fluorometric method for assay of plasma metyrapone . J Lab Clin Med 1969;74:515-520. 29. Colton T: Statistics in Medicine . Boston, Little Brown & Co Inc, 1974. 30. Grizzle JE: The two period change-over design and its use in clinical trials . Biometrics 1965;21:467-480.Crossref 31. Wallenstein S, Fisher AC: The analysis of the two-period repeated measurements crossover design with application to clinical trials . Biometrics 1977;33:261-269.Crossref 32. Brown BW Jr: The crossover experiment for clinical trials . Biometrics 1980;36:69-70.Crossref 33. Louis TA, Lavori PW, Bailer JC III, et al: Crossover and self-controlled designs in clinical research . N Engl J Med 1984;310:24-31.Crossref 34. Jubiz W, Matzukura S, Meikle AW, et al: Plasma metyrapone adrenocorticotropic hormone, cortisol and deoxycortisol levels . Arch Intern Med 1970;125:468-474.Crossref 35. Best JD, Alford FP, Donald RA: Evaluation of the three hour metyrapone test in adults . Clin Endocrinol 1980;13:69-76.Crossref 36. Sprunt JG, Browing MCK, Hannah DM: Some aspects of the pharmacology of metyrapone . Proc R Soc Med 1967;60:908-909. 37. Spiger M, Jubiz W, Meikle AW, et al: Single dose metyrapone test: Review of a four-year experience . Arch Intern Med 1975;135:698-700.Crossref 38. Southren AL, Gordon GG, Munnangi PR, et al: Altered cortisol metabolism in cells cultured from trabecular meshwork specimens obtained from patients with primary open angle glaucoma . Invest Ophthalmol Vis Sci 1983;24:1413-1417. 39. Weinstein BI, Munnangi P, Gordon GG, et al: Defects in cortisol-metabolizing enzymes in primary open angle glaucoma . Invest Ophthalmol Vis Sci 1985;26:890-893. 40. Schoneshofer M, Fenner A: Alteration of plasma levels of pituitary hormones after oral application of metyrapone . Horm Metab Res 1981;13:473-474.Crossref 41. Starka L, Hampl R, Gregorova I, et al: Aldosterone: Its occurrence, metabolism and binding in the rabbit eye . Exp Eye Res 1977;25:91-98.Crossref 42. Frenkel M, Krill AE: Effects of two mineralocorticoids and ocular tension . Arch Ophthalmol 1964;72:315-318.Crossref 43. Cole DF: Reduction in aqueous humor formation as caused by iodate, spironolactone and polyphloretin phosphate . Br J Ophthalmol 1962;46:291.Crossref 44. Starka L, Obenberger J, Louzensky G: Effect of aldactone administration into the rabbit eye . Ophthalmic Res 1981;13:160-164.Crossref 45. Waitzman MB: Aldosterone and aqueous humor dynamics . Acta Ophthalmol 1963;41:111-118.Crossref 46. Schwartz DE: The effect of spironolactone and triamterene on intraocular pressure: A negative report . Ann Ophthalmol 1974;6:105-108. 47. Schwartz B, Golden MA, Wiznia RA, et al: Differences of adrenal stress control mechanisms in subjects with glaucoma and normal subjects . Arch Ophthalmol 1981;99:1770-1777.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Jun 1, 1987

References