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. 1970 Jul;46(537):409–416. doi: 10.1136/pgmj.46.537.409

Aminoglutethimide: a ‘side-effect’ turned to therapeutic advantage

S W M Hughes, D M Burley
PMCID: PMC2467063  PMID: 4920933

Abstract

Aminoglutethimide was introduced as an anti-convulsant drug in the U.S.A. in 1960.

The occurrence of a number of side-effects, including several endocrine effects such as goitrogenesis, sexual precocity and virilization, led to its withdrawal.

Further investigation indicated that the drug inhibited adrenal biosynthesis, particularly of aldosterone, cortisol and androgens, probably by interfering with the conversion of cholesterol to delta-5-pregnenolone.

Aminoglutethimide has also been shown to modify the extra-adrenal metabolism of cortisol.

The possible clinical applications of these ‘side-effects’ are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AGUILAR J. A., MARTIN H. L., McNAUGHTON F. L. Aminoglutethimide in the treatment of epilepsy. Can Med Assoc J. 1961 Feb 18;84:374–376. [PMC free article] [PubMed] [Google Scholar]
  2. BRAY P. F. Diphenylhydantoin (dilantin) after 20 years; a review with re-emphasis by treatment of 84 patients. Pediatrics. 1959 Jan;23(1 Pt 1):151–161. [PubMed] [Google Scholar]
  3. Bochner F., Lloyd H. M., Roeser H. P., Thomas M. J. Effects of O,p'DDD and aminoglutethimide on metastatic adrenocortical carcinoma. Med J Aust. 1969 Apr 19;1(16):809–812. [PubMed] [Google Scholar]
  4. Cash R., Brough A. J., Cohen M. N., Satoh P. S. Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. J Clin Endocrinol Metab. 1967 Sep;27(9):1239–1248. doi: 10.1210/jcem-27-9-1239. [DOI] [PubMed] [Google Scholar]
  5. Cash R., Petrini M. A., Brough A. J. Ovarian dysfunction associated with an anticonvulsant drug. JAMA. 1969 May 19;208(7):1149–1152. [PubMed] [Google Scholar]
  6. Cohen M. P. Aminoglutethimide inhibition of adrenal desmolase activity. Proc Soc Exp Biol Med. 1968 Apr;127(4):1086–1090. doi: 10.3181/00379727-127-32877. [DOI] [PubMed] [Google Scholar]
  7. Dexter R. N., Fishman L. M., Ney R. L., Liddle G. W. Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action. J Clin Endocrinol Metab. 1967 Apr;27(4):473–480. doi: 10.1210/jcem-27-4-473. [DOI] [PubMed] [Google Scholar]
  8. FABISCH W. A clinical trial with a new anticonvulsant drug, alpha-(p-aminophenyl)-alpha-ethyl glutarimide preparation 16038 (Ciba). J Ment Sci. 1959 Apr;105(439):448–456. doi: 10.1192/bjp.105.439.448. [DOI] [PubMed] [Google Scholar]
  9. Fishman L. M., Liddle G. W., Island D. P., Fleischer N., Küchel O. Effects of amino-glutethimide on adrenal function in man. J Clin Endocrinol Metab. 1967 Apr;27(4):481–490. doi: 10.1210/jcem-27-4-481. [DOI] [PubMed] [Google Scholar]
  10. GIANNELLI A., GUARESCHI A., MARINATO G. L'azione di un nuovo derivato dell'imide glutarica (16038) sulla epilessia stricnica corticale. Riv Neurol. 1956 Jul-Aug;26(4):342–349. [PubMed] [Google Scholar]
  11. Gaunt R., Chart J. J., Renzi A. A. Inhibitors of adrenal cortical function. Ergeb Physiol. 1965;56:114–172. [PubMed] [Google Scholar]
  12. Gaunt R., Steinetz B. G., Chart J. J. Pharmacologic alteration of steroid hormone functions. Clin Pharmacol Ther. 1968 Sep-Oct;9(5):657–681. doi: 10.1002/cpt196895657. [DOI] [PubMed] [Google Scholar]
  13. Gorden P., Becker C. E., Levey G. S., Roth J. Efficacy of amino-glutethimide in the ectopic ACTH syndrome. J Clin Endocrinol Metab. 1968 Jun;28(6):921–923. doi: 10.1210/jcem-28-6-921. [DOI] [PubMed] [Google Scholar]
  14. Horký K., Küchel O. Aminoglutethimide (Elipten CIBA)--a new inhibitor of steroid biosynthesis. Ann Intern Med. 1969 Apr;70(4):866–867. doi: 10.7326/0003-4819-70-4-866. [DOI] [PubMed] [Google Scholar]
  15. Horký K., Küchel O., Gregorová I., Jiránková J., Matys Z. Klinische Erfahrungen mit Aminoglutäthimid (Elipten), einem neuen Inhibitor der Steroidbiosynthesis in der Nebenniere. Schweiz Med Wochenschr. 1968 Nov 23;98(47):1843–1851. [PubMed] [Google Scholar]
  16. KEBERLE H., HOFFMANN K., BERNHARD K. The metabolism of gluethimide (Doriden). Experientia. 1962 Mar 15;18:105–111. doi: 10.1007/BF02153841. [DOI] [PubMed] [Google Scholar]
  17. LAMBROS V. S. [A new anticonvulsant, elipten; a preliminary report]. Dis Nerv Syst. 1958 Aug;19(8):349–351. [PubMed] [Google Scholar]
  18. LAVECK G. D. Elipten in the treatment of organic epilepsy. Dis Nerv Syst. 1960 Apr;21:230–233. [PubMed] [Google Scholar]
  19. LIVINGSTON S., PETERSEN D., BOKS L. L. Hypertrichosis occurring in association with dilantin therapy. J Pediatr. 1955 Sep;47(3):351–352. doi: 10.1016/s0022-3476(55)80011-x. [DOI] [PubMed] [Google Scholar]
  20. LIVINGSTON S. Treatment of epilepsy with diphenylhydantoin sodium (dilantin sodium). Postgrad Med. 1956 Dec;20(6):584–590. doi: 10.1080/00325481.1956.11691354. [DOI] [PubMed] [Google Scholar]
  21. McMahon F. G., Foley J. Lack of glutethimide effect of adrenal. J Clin Endocrinol Metab. 1967 Oct;27(10):1495–1496. doi: 10.1210/jcem-27-10-1495. [DOI] [PubMed] [Google Scholar]
  22. PEARCE K. I. Elipten: A clinical evaluation of a new anticonvulsant. Preliminary report. Can Med Assoc J. 1960 May 7;82:953–959. [PMC free article] [PubMed] [Google Scholar]
  23. Philbert M., Laudat M. H., Laudat P., Bricaire H. Etude clinique et biologique d'un inhibiteur de l'hormonosynthèse cortisocurrénale: l'aminoglutéthimide. Ann Endocrinol (Paris) 1968 Mar-Apr;29(2):189–210. [PubMed] [Google Scholar]
  24. Pittman J. A., Brown R. W. Antithyroid and antiadrenocortical activity of aminoglutethimide. J Clin Endocrinol Metab. 1966 Sep;26(9):1014–1016. doi: 10.1210/jcem-26-9-1014. [DOI] [PubMed] [Google Scholar]
  25. Rallison M. L., Kumagai L. F., Tyler F. H. Goitrous hypothyroidism induced by amino-glutethimide, anticonvulsant drug. J Clin Endocrinol Metab. 1967 Feb;27(2):265–272. doi: 10.1210/jcem-27-2-265. [DOI] [PubMed] [Google Scholar]
  26. SHEEHAN S. One thousand cases of late onset epilepsy. Ir J Med Sci. 1958 Jun;(390):261–272. doi: 10.1007/BF02951579. [DOI] [PubMed] [Google Scholar]
  27. SPARBERG M. DIAGNOSTICALLY CONFUSING COMPLICATIONS OF DIPHENYLHYDANTOIN THERAPY. A REVIEW. Ann Intern Med. 1963 Dec;59:914–930. doi: 10.7326/0003-4819-59-6-914. [DOI] [PubMed] [Google Scholar]
  28. Schteingart D. E., Cash R., Conn J. W. Amino-glutethimide and metastatic adrenal cancer. Maintained reversal (six months) of Cushing's syndrome. JAMA. 1966 Nov 28;198(9):1007–1010. [PubMed] [Google Scholar]
  29. Schteingart D. E., Conn J. W. Effects of aminoglutethimide upon adrenal function and cortisol metabolism in Cushing's syndrome. J Clin Endocrinol Metab. 1967 Dec;27(12):1657–1666. doi: 10.1210/jcem-27-12-1657. [DOI] [PubMed] [Google Scholar]
  30. Smilo R. P., Earll J. M., Forsham P. H. Suppression of tumorous adrenal hyperfunction by aminoglutethimide. Metabolism. 1967 Apr;16(4):374–377. doi: 10.1016/0026-0495(67)90048-0. [DOI] [PubMed] [Google Scholar]
  31. VERDEAU-PAILLES J. [A new anticonvulsant: the preparation Ciba 16-0-38 or elipten. Its importance in refractory epilepsy]. Ann Med Psychol (Paris) 1961 Mar;119(1):501–518. [PubMed] [Google Scholar]
  32. WEISENFELD S., GOLDNER M. G. Treatment of advanced malignancy and Cushing's syndrome with DDD. Cancer Chemother Rep. 1962 Feb;16:335–339. [PubMed] [Google Scholar]
  33. WERK E. E., Jr, MACGEE J., SHOLITON L. J. EFFECT OF DIPHENYLHYDANTOIN ON CORTISOL METABOLISM IN MAN. J Clin Invest. 1964 Sep;43:1824–1835. doi: 10.1172/JCI105056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Woods J. W., Liddle G. W., Michelakis A. M., Brill A. B. Effect of an adrenal inhibitor in hypertensive patients with suppressed renin. Arch Intern Med. 1969 Apr;123(4):366–370. [PubMed] [Google Scholar]
  35. Zavadil M., Schreiber V., Kmentová-Zbuzková V. Die Veränderungen am Ovarium von Ratten nach Applikation von Aminoglutethimid (Elipten-CIBA) Endokrinologie. 1968;53(5):405–411. [PubMed] [Google Scholar]

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