Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1978 May;187(5):475–484. doi: 10.1097/00000658-197805000-00004

Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma.

S A Wells Jr, R J Santen, A Lipton, D E Haagensen Jr, E J Ruby, H Harvey, W G Dilley
PMCID: PMC1396547  PMID: 646874

Abstract

The use of adrenalectomy and hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma is reserved for highly selected patients. As an alternate approach, a pharmacologic method of inhibiting adrenal cortical secretion was developed which consisted of the daily administration of 1000 mg of aminoglutethimide to block steroidogensis and either dexamethasone (2.0-3.0 mg/day) or hydrocortisone (40-60 mg/day) as replacement glucocorticoid. This regimen markedly suppressed plasma levels of DHA-S, androstenedione, estrone, and estradiol, and urinary levels of aldosterone. Of 50 patients treated, 19 (38%) demonstrated either a complete (8/19) or a partial (11/19) objective disease remission which lasted for 18.05 +/- 3.1 months (mean +/- SEM). In 10 (20%) patients, there was stabilization of disease (7.8 +/- 1.2 months), accompanied by symptomatic relief of bone pain in six (12%). There was disease progression in 20 (40%) patients. The acute side effects of aminoglutethimide therapy were significant and consisted of transient lethargy (41.5%) and a cutaneous rash (35.8%). Chronic toxicity was negligible. The medical adrenalectomy regimen of aminoglutethimide plus glucocorticoid offers a suitable alternative to surgical adrenalectomy or hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma.

Full text

PDF

Images in this article

478Fig. 1a and b.
on p.478
479Fig. 2a-f.
on p.479
480Fig. 3a-d.
on p.480
482Fig. 4.
on p.482

Selected References

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

  1. Abraham G. E., Chakmakjian Z. H. Serum steroid levels during the menstrual cycle in a bilaterally adrenalectomized woman. J Clin Endocrinol Metab. 1973 Oct;37(4):581–587. doi: 10.1210/jcem-37-4-581. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. DAICOFF G. R., HARMON R., VAN PROHASKA J. Effect of adrenalectomy on mammary carcinoma. Arch Surg. 1962 Nov;85:800–807. doi: 10.1001/archsurg.1962.01310050102016. [DOI] [PubMed] [Google Scholar]
  4. DAO T. L., TAN E., BROOKS V. A comparative evaluation of adrenalectomy and cortisone in the treatment of advanced mammary carcinoma. Cancer. 1961 Nov-Dec;14:1259–1265. doi: 10.1002/1097-0142(196111/12)14:6<1259::aid-cncr2820140616>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  5. Demers L. M., Abt W. J., Krieg A. F. A new combined thyroid hormone index based on thyroxine, triiodothyronine and resin uptake. Am J Clin Pathol. 1976 Mar;65(3):356–359. doi: 10.1093/ajcp/65.3.356. [DOI] [PubMed] [Google Scholar]
  6. Edelstyn G., Gleadhill C., Lyons A. Total hypophysectomy for advanced breast cancer. Clin Radiol. 1968 Oct;19(4):426–432. doi: 10.1016/s0009-9260(68)80099-6. [DOI] [PubMed] [Google Scholar]
  7. FORREST A. P. ENDOCRINE TREATMENT OF BREAST CANCER. Isr J Med Sci. 1965 Mar;1:259–271. [PubMed] [Google Scholar]
  8. Fracchia A. A., Randall H. T., Farrow J. H. The results of adrenalectomy in advanced breast cancer in 500 consecutive patients. Surg Gynecol Obstet. 1967 Oct;125(4):747–756. [PubMed] [Google Scholar]
  9. Griffiths C. T., Hall T. C., Saba Z., Barlow J. J., Nevinny H. B. Preliminary trial of aminoglutethimide in breast cancer. Cancer. 1973 Jul;32(1):31–37. doi: 10.1002/1097-0142(197307)32:1<31::aid-cncr2820320104>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  10. Grodin J. M., Siiteri P. K., MacDonald P. C. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab. 1973 Feb;36(2):207–214. doi: 10.1210/jcem-36-2-207. [DOI] [PubMed] [Google Scholar]
  11. MURPHY B. P., ENGELBERG W., PATTEE C. J. Simple method for the determination of plasma corticoids. J Clin Endocrinol Metab. 1963 Mar;23:293–300. doi: 10.1210/jcem-23-3-293. [DOI] [PubMed] [Google Scholar]
  12. Odell W. D., Wilber J. F., Paul W. E. Radioimmunoassay of thyrotropin in human serum. J Clin Endocrinol Metab. 1965 Sep;25(9):1179–1188. doi: 10.1210/jcem-25-9-1179. [DOI] [PubMed] [Google Scholar]
  13. PEARSON O. H., RAY B. S. Results of hypophysectomy in the treatment of metastatic mammary carcinoma. Cancer. 1959 Jan-Feb;12(1):85–92. doi: 10.1002/1097-0142(195901/02)12:1<85::aid-cncr2820120114>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  14. Rees L. H., Cook D. M., Kendall J. W., Allen C. F., Kramer R. M., Ratcliffe J. G., Knight R. A. A radioimmunoassay for rat plasma ACTH. Endocrinology. 1971 Jul;89(1):254–261. doi: 10.1210/endo-89-1-254. [DOI] [PubMed] [Google Scholar]
  15. Samojlik E., Santen R. J., Wells S. A. Adrenal suppression with aminoglutethimide. II. Differential effects of aminoglutethimide on plasma androstenedione and estrogen levels. J Clin Endocrinol Metab. 1977 Sep;45(3):480–487. doi: 10.1210/jcem-45-3-480. [DOI] [PubMed] [Google Scholar]
  16. Sampson E. J., Derck D. D., Demers L. M. Comparison of two radioimmunoassay kits for aldosterone determination. Clin Biochem. 1976 Aug;9(4):216–221. doi: 10.1016/s0009-9120(76)80061-6. [DOI] [PubMed] [Google Scholar]
  17. Santen R. J., Lipton A., Kendall J. Successful medical adrenalectomy with amino-glutethimide. Role of altered drug metabolism. JAMA. 1974 Dec 23;230(12):1661–1665. [PubMed] [Google Scholar]
  18. Santen R. J., Samojlik E., Lipton A., Harvey H., Ruby E. B., Wells S. A., Kendall J. Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Cancer. 1977 Jun;39(6 Suppl):2948–2958. doi: 10.1002/1097-0142(197706)39:6<2948::aid-cncr2820390681>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  19. Santen R. J., Wells S. A., Cohn N., Demers L. M., Misbin R. I., Foltz E. L. Compensatory increase in TSH secretion without effect on prolactin secretion in patients treated with aminoglutethimide. J Clin Endocrinol Metab. 1977 Oct;45(4):739–746. doi: 10.1210/jcem-45-4-739. [DOI] [PubMed] [Google Scholar]
  20. Santen R. J., Wells S. A., Runić S., Gupta C., Kendall J., Rudy E. B., Samojlik E. Adrenal suppression with aminoglutethimide. I. Differential e-fects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone. J Clin Endocrinol Metab. 1977 Sep;45(3):469–479. doi: 10.1210/jcem-45-3-469. [DOI] [PubMed] [Google Scholar]
  21. Smithline F., Sherman L., Kolodny D. Prolactin and breast carcinoma. N Engl J Med. 1975 Apr 10;292(15):784–792. doi: 10.1056/NEJM197504102921506. [DOI] [PubMed] [Google Scholar]
  22. Thompson E. A., Jr, Siiteri P. K. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J Biol Chem. 1974 Sep 10;249(17):5364–5372. [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES