Summary
Could aminoglutethimide replace adrenalectomy? This question has already been answered in clinical practice in the United Kingdom, for surgical adrenalectomy has declined markedly in frequency as new hormonal therapy has appeared. An optimal assessment of an endocrine therapy can only be made in previously untreated patients because of the heterogeneity of previously treated populations. Thus aminoglutethimide (AG) and adrenalectomy have been compared for previously untreated and treated populations. Because AG is commonly called ‘medical adrenalectomy’, this article will review and compare aminoglutethimide therapy with surgical adrenalectomy and make the case that surgical adrenalectomy is no longer indicated in the management of breast cancer.
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References
Hughes SWM, Burley DM: Aminoglutethimide. A ‘sideeffect’ turned to therapeutic advantage. Postgrad Med J 46:409, 1970
Rallison ML, Kumagai LF, Tyler FH: Goitrous hypothyroidism induced by aminoglutethimide, anticonvulsant drug. J Clin Endocrinol Metab 27:265, 1967
Pittmann JA, Brown RW: Antithyroid and antiadrenocorticoid activity of aminoglutethimide. J Clin Endocrinol Metab 26:1014, 1966
Cash R, Petrini MA, Brough AJ: Ovarian dysfunction associated with an anticonvulsant drug. JAMA 208:1149, 1969
Cash R, Brough AJ, Cohen MNP, Satoh PS: Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis. Mechanism of action and therapeutic trial. J Clin Endocrinol Metab 27:1239, 1967
Santen RJ, Lipton A, Kendall J: Successful medical adrenalectomy with aminoglutethimide. Role of altered drug metabolism. JAMA 230:1661, 1974
Harris AL, Dowsett M, Smith IE, Jeffcoate SL: Endocrine effects of low dose aminoglutethimide alone in advanced postmenopausal breast cancer. Brit J Cancer 47:621, 1983
Touitou Y, Bogdan A, Legrand JC, Desgrez P: Aminoglutethimide and glutethimide: Effects on 18-hydroxycorticosterone biosynthesis by human and sheep adrenals in vitro. Acta Endocrinol 80:517, 1975
Fishman LM, Liddle GW, Island DF, FLeischer N, Kuchel O: Effects of aminoglutethimide on adrenal function in man. J Clin Endocrinol Metab 27:481, 1967
Santen RJ, Wells SA Jr: The use of aminoglutethimide in the treatment of patients with metastatic carcinoma of the breast. Cancer 46:1066, 1980
Kowal J: Adrenal cells in tissue culture. IV. Use of an inhibitor of steroid synthesis for the study of ACTH action. Endocrinol 85:270, 1969
Dexter RN, Fishmann LM, Ney RL, Liddle GW: Inhibition of adrenal corticosteroid synthesis by aminoglutethimide. Studies of the mechanism of action. J Clin Endocrinol Metab 27:473, 1967
Gower DB: Modifiers of steroid-hormone metabolism. A review of their chemistry, biochemistry and clinical applications. J Steroid Biochem 5:501, 1974
Samojlik E, Santen RJ: Adrenal suppression with aminoglutethimide. III. Comparison of plasma Δ4 and Δ5-steroids in postmenopausal women treated for breast carcinoma. J Clin Endocrinol Metab 47:717, 1978
Harris AL, Dowsett M, Smith IE, Jeffcoate S: Hydrocortisone alone versus hydrocortisone plus aminoglutethimide: A comparison of the endocrine effects in postmenopausal breast cancer. Eur J Cancer 20:463, 1984
Bird CE, Masters VE, Sterns EE, Clark AF: Effects of aminoglutethimide on Δ5-androstenediol metabolism in postmenopausal women with breast cancer. Cancer Res 42:4797, 1982
Vermeulen A, Paridaens R, Heuson JC: Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol 19:673, 1983
Badder EM, Lerman S, Santen R: Aminoglutethimide stimulates extra adrenal Δ4-androstenedione production. J Surg Res 34:380, 1983
Grodin JM, Siiteri PK, MacDonald PC: Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab 36:207, 1973
Poortman J, Thijssen JHH, Schwarz F: Androgen production and conversion to estrogens in normal postmenopausal women and in selected breast cancer patients. J Clin Endocrinol Metab 37:101, 1973
Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, Ruby E: Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257, 1978
Graves PE, Salhanick HA: Stereoselective inhibition of aromatase by enantiomers of aminoglutethimide. Endocrinol 105:52, 1979
Miller WR, Hawkins RA, Forrest APM: Significance of aromatase activity in human breast cancer. Cancer Res 42 (Suppl) 3365S, 1982
Perel E, Blackstein ME, Killinger DW: Aromatase in human breast carcinoma. Cancer Res 42 (Suppl):3369S, 1982
Abul-Hajj, YJ: Comparative studies of aromatase inhibitors in relation to the significance of estrogen synthesis in human mammary tumours. Cancer Res 42 (Suppl):3373S, 1982
Santen RJ, Santner SJ, Tilsen-Mallett N, Rosen HR, Samojlik E, Veldhuis JD:In vivo andin vitro pharmacological studies of aminoglutethimide as an aromatase inhibitor. Cancer Res 42 (Suppl):3357S, 1982
Samojlik E, Santen RJ, Worgul TJ: Plasma estrone-sulphate. Assessment of reduced estrogen production during treatment of metastatic breast cancer. Steroids 39:497, 1982
Santen RJ, Wells SA, Cohn N, Demers LM, Misbin RI, Folts EL: Compensatory increase in TSH secretion without effect on prolactin secretion in patients treated with aminoglutethimide. J Clin Endocrinol Metab 45:739, 1977
Maclouf J, Sors H, Rigaud M: Recent aspects of prostaglandin biosynthesis: A review. Biomed 26:362, 1977
Harris AL, Mitchell MD, Smith IE, Powles TJ: Suppression of plasma 6-ketoprostaglandin F1α and 13, 14-dihydro-15-ketoprostaglandin F2α by aminoglutethimide in advanced breast cancer. Brit J Cancer 48:595, 1983
Santen RJ, Samojlik E, Wells SA: Resistance of the ovary to blockade of aromatization with aminoglutethimide. J Clin Endocrinol Metab 51:473, 1980
Harris AL, Dowsett M, Jeffcoate SL, McKinna JA, Morgan M, Smith IE: Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. J Clin Endocrinol Metab 55:718, 1982
Nicholls PJ, Dalrymple PD, Eweiss N, Douglas JS: Aminoglutethimide metabolism and pharmacokinetics. 13th Intl Congr Chemother (Aug 28-Sept 2, Vienna) SY96, 1983
Thompson TA, Vermeulen JD, Wagner WE, Lesher AR: Aminoglutethimide bioavailability, pharmacokinetics and binding to blood constituents. J Pharm Sci 70:1040, 1981
Murray FT, Santner S, Samojlik EA, Santen RJ: Serum aminoglutethimide levels: Studies of serum half-life, clearance and patient compliance. J Clin Pharmacol 19:704, 1979
Mauri M, Nunziata C, Gamucci T, Natali M, Calabresi F: GGT elevation associated with aminoglutethimide therapy in advanced breast cancer. 2nd Eur Conf Clin Oncol Abst 17, 1983
Schteingart DE, Conn JW: Effects of aminoglutethimide upon adrenal function and cortisol metabolism in Cushing's syndrome. J Clin Endocrinol Metab 27:1657, 1967
Jarman M, Foster AB, Goss PE, Griggs LJ, Howe I, Coombes RC: Metabolism of aminoglutethimide in humans: Identification of N-hydroxylaminoglutethimide as an autoinduced metabolite. Biomed Mass Spectrum (In press)
Coombes RC, Foster AB, Harland SJ, Jarman M, Nicer EC: Polymorphically acetylated aminoglutethimide in humans. Brit J Cancer 46:340, 1982
Brunning PF, Bonfrer JGM: Aminoglutethimide and oral anticoagulant therapy. Lancet ii:582, 1983
Uzgiris VI, Whipple CA, Salhanick HA: Stereoselective inhibition of cholesterol side chain cleavage by enantiomers of aminoglutethimide. Endocrinol 101:89, 1977
Worgul TJ, Santen RJ, Samojlik E, Wells SA: How effective is surgical adrenalectomy on lowering steroid hormone concentrations? J Clin Endocrinol Metab 54:22, 1982
Bolufer P, Antonio P, Garcia R, Munoz J, Rodriguez A, Romeu A: Role of the ovary in the regulation of sex hormone binding globulin and its contribution to peripheral levels of androstenedione. Exp Clin Endocrinol 82:29, 1983
Paicoff GR, Harmon R, Van Prohasaka J: Effect of adrenalectomy on mammary carcinoma. Arch Surg 85:800, 1962
Atkins H, Bulbrook RD, Falconer MA, Hayward JL, MacLean KC, Schurr PH: Urinary steroids in the prediction of response to adrenalectomy or hypophysectomy. Lancet ii:1261, 1968
Fraccia AA, Farrow JH, Miller TR, Tollefsen RH, Greenberg EJ, Knapper WH: Hypophysectomy as compared with adrenalectomy in the treatment of advanced carcinoma of the breast. Surg Gynaecol Obstet 133:241, 1971
Byron R, Yonemoto RH, Bashore R, Bierman HR, Cronemiller P, Masters H: Bilateral adrenalectomy in advanced breast carcinoma. Surgery 52:725, 1962
Bennett RC: Long-term follow-up of surgical adrenalectomy for breast cancer. Aust NZ J Surg 53:415, 1983
Yonemoto RH, Tan MSC, Byron RL, Riihimaki DU, Keating J, Jacobs W: Randomised sequential hormonal therapy vs. adrenalectomy for metastatic breast carcinoma. Cancer 39:547, 1977
Cade S: Adrenalectomy for disseminated breast cancer. Brit Med J ii:613, 1966
Dao TLY, Huggins C: Bilateral adrenalectomy in the treatment of cancer of the breast. Arch Surg 71:645, 1955
Hellstrom J, Franksson C: Adrenalectomy in cancer of the breast. In: Currie AR, Illingworth CFW (eds): Endocrine Aspects of Breast Cancer. Livingstone, 1958, p. 5
Harris AL, Powles TJ, Smith IE, Coombes RC, Ford HT, Gazet JC, Harmer CL, Morgan M, White H, Parsons CA, McKinna JA: Aminoglutethimide for the treatment of advanced postmenopausal breast cancer. Eur J Cancer Clin Oncol 19:11, 1983
Smith IE, Harris AL, Morgan M, Ford HT, Gazet JC, Harmer CL, White H, Parsons CA, Villards A, Walsh G, McKinna JA: Tamoxifen versus aminoglutethimide in the treatment of advanced breast carcinoma: A control randomised cross-over trial. Brit Med J 283:1432, 1981
Gale KE: Treatment of advanced breast cancer with aminoglutethimide. A 14 year experience. Cancer Res 42 (Suppl):3389S, 1982
Murray RML, Pitt P: Aminoglutethimide in tamoxifenresistant patients: the Melbourne experience. Cancer Res 42 (Suppl):3437S, 1982
Santen RJ, Worgul TJ, Harvey H, Lipton A, Boucher A, Samojlik E, Wells S: Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma: Correlation of clinical and hormonal responses. Ann Intern Med 96:94, 1982
Lipton A, Harvey HA, Santen RJ, Boucher A, White D, Bernath A, Dixon R, Richards G, Shafik A: A randomised trial of aminoglutethimide versus tamoxifen in metastatic breast cancer. Cancer 50:2265, 1982
Troner MB: Aminoglutethimide in the treatment of metastatic breast cancer. Cancer Res 42 (Suppl):3402S, 1982
Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA: A randomised trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med 305: 545, 1981
McDonald I. Endocrine ablation in disseminated mammary carcinoma. Surg Gynecol Obstet 115:215, 1962
Nemoto T, Patel J, Rosner D, Dao TL: Tamoxifen versus adrenalectomy in metastatic breast cancer. Cancer 53:1333, 1984
Dao TL, Nemoto T: Steroid receptors and response to endocrine ablations in women with metastatic cancer of the breast. Cancer 46:2779, 1980
Byar DP, Sears ME, McGuire WL: Relationship between oestrogen receptor values and clinical data in predicting the response to endocrine therapy for patients with advanced breast cancer. Eur J Cancer 15:299, 1979
Lawrence DV, Lipton A, Harvey HA, Santen RJ, Wells SA Jr, Cox CE, White DS: Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide. Cancer 45:786, 1980
Paridaens R, Leclerq G, Heuson JC: Estrogen receptor status and the clinical response to a combination of aminoglutethimide and cortisol in advanced breast cancer. Rec Results Cancer Res 91:248, 1984
Gale KE, Gelman R, Tormey D, Cummings F: Hormone therapy for metastatic breast cancer. Proc Am Soc Clin Oncol 2:C409, 1983
Samojlik E, Santen RJ, Worgul TJ: Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophysectomy or adrenalectomy. Clin Endocrinol 20:43, 1984
Newsome HH, Brown PW, Terz JJ, Lawrence W Jr: Medical adrenalectomy and plasma steroids in advanced breast carcinoma. Surgery 83:83, 1978
Buzdar AV, Powell KC, Legha SS, Blumenschein GR: Treatment of advanced breast cancer with aminoglutethimide after therapy with tamoxifen. Cancer 50:1708, 1982
Kaye SB, Woods RL, Fox RM, Coates AS, Tattersall MHN: Use of aminoglutethimide as second-line endocrine therapy in metastatic breast cancer. Cancer Res 42 (Suppl): 3445S, 1982
Paterson AG, Webster DJT: Adrenalectomy for advanced breast cancer: A reappraisal. Anticancer Res 3:151, 1983
Tilson-Mallett N, Santner SJ, Feil PD, Santen RJ: Biological significance of aromatase activity in human breast tumours. J Clin Endocrinol Metab 57:1125, 1983
Prost O, Turrel MO, Dahan N, Cravener C, Adessi GL: Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulphate levels in human breast carcinoma. Cancer Res 44:661, 1984
Harris AL, Dowsett M, Smith IE, Jeffcoate SL: Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer. Brit J Cancer 48:449, 1983
Dowsett M, Harris AL, Smith IE, Jeffcoate SL: Endocrine changes associated with relapse in advanced breast cancer patients on aminoglutethimide therapy. J Clin Endocrinol Metab 58:99, 1984
Nickelsen T, Schulz F, Demisch K: Studies on cortisol substitution therapy in patients with adrenal insufficiency. Exp Clin Endocrinol 82:35, 1983
Worgul TJ, Santen RJ: Recovery of the hypothalamicpituitary-adrenal axis after long term suppression by aminoglutethimide and hydrocortisone. 62nd Annu Meet Endocrine Soc, Washington: Abst 810, 1980
Cantwell BMJ, Sainsbury JRC, Harris AL, Wilson RG, Farndon J, Dawes PJDK, Dowsett M: Low dose aminoglutethimide. Phase II study in advanced postmenopausal breast cancer. Brit J Cancer 50:252, 1984
Bonterre J, Coppens H, Mauriac L, Mathieu M, Roverre J, Armand JP, Fargeot J, Metz M, Tubiana M, Cappelaere P: Aminoglutethimide 1 G v 500 mg in advanced breast cancer. III ECCO Conference, Abs 252, 1985
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Harris, A.L. Could aminoglutethimide replace adrenalectomy?. Breast Cancer Res Tr 6, 201–211 (1985). https://doi.org/10.1007/BF01806770
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DOI: https://doi.org/10.1007/BF01806770