Skip to main content
NCBI home page
Annals of Surgery logoLink to Annals of Surgery
. 1982 Sep;196(3):246–258. doi: 10.1097/00000658-198209000-00003

Surgical management of the ectopic ACTH syndrome.

C J Davies, G F Joplin, R B Welbourn
PMCID: PMC1352592  PMID: 6287949

Abstract

Most patients with extra-pituitary ACTH-secreting tumors die from carcinoma, but a few can benefit from operation. Of 96 patients with Cushing's syndrome, 11 probably had such tumors. There were three modes of presentation: (1) three had malignant tumors with visceral metastases initially. One (bronchial carcinoid) died without operation. Two with carcinoma (thyroid medullary and islet-cell) underwent adrenalectomy with remission, but died soon. (2) three had apparently benign tumors initially. One (appendicular carcinoid) underwent appendectomy and one (bronchial carcinoid with hilar node metastases) underwent lobectomy. Both had rapid remissions. The third (pheochromocytoma) died after resection of the tumor. (3) five patients had no obvious tumors and underwent adrenalectomy with remission. In one a benign bronchial carcinoid was removed later. Four others remain well, but without localizing signs of tumor. The main biochemical features in all were hypokalemic alkalosis and very high urinary excretion of free cortisol. Seven of the eight patients without visceral metastases are in remission from one to 15 years after operation.

Full text

PDF
246

Images in this article

252Fig. 1.
on p.252
252Fig. 2.
on p.252
253Fig. 3.
on p.253
254Fig. 4.
on p.254
254Fig. 5.
on p.254
255Fig. 6.
on p.255

Selected References

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

  1. Adams E. F., Ashby M. J., Brown S. M., White M. C., Mashiter K. Bromocriptine suppresses ACTH secretion from human pituitary tumour cells in culture by a dopaminergic mechanism. Clin Endocrinol (Oxf) 1981 Nov;15(5):479–484. doi: 10.1111/j.1365-2265.1981.tb00691.x. [DOI] [PubMed] [Google Scholar]
  2. Azzopardi J. G., Williams E. D. Pathology of 'nonendocrine' tumors associated with Cushing's syndrome. Cancer. 1968 Aug;22(2):274–286. doi: 10.1002/1097-0142(196808)22:2<274::aid-cncr2820220204>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  3. Bailey R. E. Periodic hormonogenesis--a new phenomenon. Periodicity in function of a hormone-producing tumor in man. J Clin Endocrinol Metab. 1971 Mar;32(3):317–327. doi: 10.1210/jcem-32-3-317. [DOI] [PubMed] [Google Scholar]
  4. Belchetz P. E., Brown C. L., Makin H. L., Trafford D. J., Mason A. S., Bloom S. R., Ratcliffe J. G. ACTH, glucagon and gastrin production by a pancreatic islet cell carcinoma and its treatment. Clin Endocrinol (Oxf) 1973 Oct;2(4):307–316. doi: 10.1111/j.1365-2265.1973.tb01716.x. [DOI] [PubMed] [Google Scholar]
  5. Bigos S. T., Robert F., Pelletier G., Hardy J. Cure of Cushing's disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica. J Clin Endocrinol Metab. 1977 Dec;45(6):1251–1260. doi: 10.1210/jcem-45-6-1251. [DOI] [PubMed] [Google Scholar]
  6. CHRISTY N. P. Adrenocorticotrophic activity in the plasma of patients with Cushing's syndrome associated with pulmonary neoplasms. Lancet. 1961 Jan 14;1(7168):85–86. doi: 10.1016/s0140-6736(61)92125-0. [DOI] [PubMed] [Google Scholar]
  7. Carey R. M., Orth D. N., Hartmann W. H. Malignant melanoma with ectopic production of adrenocorticotropic hormone. Palliative treatment with inhibitors of adrenal steroid biosynthesis. J Clin Endocrinol Metab. 1973 Mar;36(3):482–487. doi: 10.1210/jcem-36-3-482. [DOI] [PubMed] [Google Scholar]
  8. Craig I. D., Nelson P. G. Pancreatic islet-cell tumour associated with Cushing's syndrome. Report of a case with estimation of tumour ACTH content. Ulster Med J. 1975;44(1):68–70. [PMC free article] [PubMed] [Google Scholar]
  9. Dirschmid K., Weichselbaumer W. Medulläres Schilddrüsenkarzinom mit Cushing-Syndrom. Monatsschr Ohrenheilkd Laryngorhinol. 1972 Oct;106(10):491–497. [PubMed] [Google Scholar]
  10. Drury P. L., Ratter S., Tomlin S., Williams J., Dacie J. E., Rees L. H., Besser G. M. Experience with selective venous sampling in diagnosis of ACTH-dependent Cushing's syndrome. Br Med J (Clin Res Ed) 1982 Jan 2;284(6308):9–12. doi: 10.1136/bmj.284.6308.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eddy R. L., McMurry J. F., Jr, Best E. B., Henderson B. W., Smith V. T. Adrenal ablation by venous catheter. Ann Intern Med. 1973 Aug;79(2):273–274. doi: 10.7326/0003-4819-79-2-273. [DOI] [PubMed] [Google Scholar]
  12. Gabrilove J. L., Nicolis G. L., Kirschner P. A. Cushing's syndrome in association with carcinoid tumor. Ann Surg. 1969 Feb;169(2):240–248. doi: 10.1097/00000658-196902000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gillies G., Ratter S., Grossman A., Gaillard R., Lowry P. J., Besser G. M., Rees L. H. Secretion of ACTH, LPH and beta-endophin from human pituitary tumours in vitro. Clin Endocrinol (Oxf) 1980 Aug;13(2):197–205. doi: 10.1111/j.1365-2265.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
  14. HARRISON M. T., MONTGOMERY D. A., RAMSEY A. S., ROBERTSON J. H., WELBOURN R. B. Cushing's syndrome with carcinoma of bronchus and with features suggesting carcinoid tumour. Lancet. 1957 Jan 5;272(6958):23–25. doi: 10.1016/s0140-6736(57)92437-6. [DOI] [PubMed] [Google Scholar]
  15. Himsworth R. L., Bloomfield G. A., Coombes R. C., Ellison M., Gilkes J. J., Lowry P. J., Setchell K. D., Slavin G., Rees L. H. 'Big ACTH' and calcitonin in an ectopic hormone secreting tumour of the liver. Clin Endocrinol (Oxf) 1977 Jul;7(1):45–62. doi: 10.1111/j.1365-2265.1977.tb02939.x. [DOI] [PubMed] [Google Scholar]
  16. Hirata Y., Sakamoto N., Yamamoto H., Matsukura S., Imura H., Okada S. Gastric carcinoid with ectopic production of ACTH and beta-MSH. Cancer. 1976 Jan;37(1):377–385. doi: 10.1002/1097-0142(197601)37:1<377::aid-cncr2820370148>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  17. Hirata Y., Sakamoto N., Yamamoto H., Matsukura S., Imura H., Okada S. Gastric carcinoid with ectopic production of ACTH and beta-MSH. Cancer. 1976 Jan;37(1):377–385. doi: 10.1002/1097-0142(197601)37:1<377::aid-cncr2820370148>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  18. Imura H. Ectopic hormone syndromes. Clin Endocrinol Metab. 1980 Jul;9(2):235–260. doi: 10.1016/s0300-595x(80)80032-6. [DOI] [PubMed] [Google Scholar]
  19. Joffe S. N., Elias E., Rehfeld J. F., Polak J. M., Bloom S. R., Welbourn R. B. Clinically silent gross hypergastrinaemia from a multiple hormone-secreting pancreatic apudoma. Br J Surg. 1978 Apr;65(4):277–280. doi: 10.1002/bjs.1800650417. [DOI] [PubMed] [Google Scholar]
  20. Johnston W. H., Waisman J. Carcinoid tumor of the vermiform appendix with cushing's syndrome. Ultrastructural study of a case. Cancer. 1971 Mar;27(3):681–686. doi: 10.1002/1097-0142(197103)27:3<681::aid-cncr2820270325>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  21. Keusch G., Binswanger U., Dambacher M. A., Fischer J. A. Ectopic ACTH syndrome and medullary thyroid carcinoma. Acta Endocrinol (Copenh) 1977 Oct;86(2):306–316. doi: 10.1530/acta.0.0860306. [DOI] [PubMed] [Google Scholar]
  22. Kitchens C. S., Alexander R. W. Cushing's syndrome secondary to a neuroendocrine tumor: relapse after bilateral adrenalectomy. Cancer. 1981 Oct 15;48(8):1873–1876. doi: 10.1002/1097-0142(19811015)48:8<1873::aid-cncr2820480826>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  23. Kuwayama A., Kageyama N., Nakane T., Takanohashi M., Okada C., Kanie N., Hara I., Tomita A. [Treatment of Cushing's disease by transsphenoidal microsurgery (author's transl)]. Neurol Med Chir (Tokyo) 1978 Jun;18(4):279–285. doi: 10.2176/nmc.18pt2.279. [DOI] [PubMed] [Google Scholar]
  24. Kyriakides G. K., Silvis S. E., Ahmed M., Vennes J. A., Vogel S. B. Gastrinoma associated with common bile duct obstruction and the ectopic production of ACTH. Am J Surg. 1979 Jun;137(6):800–802. doi: 10.1016/0002-9610(79)90098-9. [DOI] [PubMed] [Google Scholar]
  25. LIDDLE G. W. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1960 Dec;20:1539–1560. doi: 10.1210/jcem-20-12-1539. [DOI] [PubMed] [Google Scholar]
  26. Liddle G. W., Nicholson W. E., Island D. P., Orth D. N., Abe K., Lowder S. C. Clinical and laboratory studies of ectopic humoral syndromes. Recent Prog Horm Res. 1969;25:283–314. doi: 10.1016/b978-0-12-571125-8.50009-0. [DOI] [PubMed] [Google Scholar]
  27. Luton J. P., Thieblot P., Bricaire H. Association syndrome de Cushing-phéochromocytome. Nouv Presse Med. 1977 Dec 17;6(43):4053–4057. [PubMed] [Google Scholar]
  28. MACPHEE I. W. Cushing's syndrome associated with carcinoma of the bronchus. Br J Surg. 1959 Mar;46(199):456–458. doi: 10.1002/bjs.18004619908. [DOI] [PubMed] [Google Scholar]
  29. MEADOR C. K., LIDDLE G. W., ISLAND D. P., NICHOLSON W. E., LUCAS C. P., NUCKTON J. G., LUETSCHER J. A. Cause of Cushing's syndrome in patients with tumors arising from "nonendocrine" tissue. J Clin Endocrinol Metab. 1962 Jul;22:693–703. doi: 10.1210/jcem-22-7-693. [DOI] [PubMed] [Google Scholar]
  30. Mason A. M., Ratcliffe J. G., Buckle R. M., Mason A. S. ACTH secretion by bronchial carcinoid tumours. Clin Endocrinol (Oxf) 1972 Jan;1(1):3–25. doi: 10.1111/j.1365-2265.1972.tb00374.x. [DOI] [PubMed] [Google Scholar]
  31. Melvin K. E., Tashjian A. H., Jr, Cassidy C. E., Givens J. R. Cushing's syndrome caused by ACTH- and calcitonin-secreting medullary carcinoma of the thyroid. Metabolism. 1970 Oct;19(10):831–838. doi: 10.1016/0026-0495(70)90080-6. [DOI] [PubMed] [Google Scholar]
  32. O'Neal L. W., Kipnis D. M., Luse S. A., Lacy P. E., Jarett L. Secretion of various endocrine substances by ACTH-secreting tumors--gastrin, melanotropin, norepinephrine, serotonin, parathormone, vasopressin, glucagon. Cancer. 1968 Jun;21(6):1219–1232. doi: 10.1002/1097-0142(196806)21:6<1219::aid-cncr2820210625>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  33. Pullan P. T., Clement-Jones V., Corder R., Lowry P. J., Besser G. M., Rees L. H. ACTH LPH and related peptides in the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1980 Nov;13(5):437–445. doi: 10.1111/j.1365-2265.1980.tb03409.x. [DOI] [PubMed] [Google Scholar]
  34. Ratcliffe J. G., Knight R. A., Besser G. M., Landon J., Stansfeld A. G. Tumor and plasma ACTH concentrations in patients with and without the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1972 Jan;1(1):27–44. doi: 10.1111/j.1365-2265.1972.tb00375.x. [DOI] [PubMed] [Google Scholar]
  35. Ratter S. J., Lowry P. J., Besser G. M., Rees L. H. Chromatographic characterization of adsrenocorticotrophin in human plasma. J Endocrinol. 1980 Jun;85(3):359–369. doi: 10.1677/joe.0.0850359. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Rosenstock J., Allison D., Joplin G. F., Lewis P. D., Mashiter K., Welbourn R. B., White M. C. Therapeutic adrenal venous infarction in ACTH-dependent Cushing's syndrome. Br J Radiol. 1981 Oct;54(646):912–915. doi: 10.1259/0007-1285-54-646-912. [DOI] [PubMed] [Google Scholar]
  38. Smith A. H., Whayne T. F., Young M. A., Mattison B. F., Troupin J. L., Diefenbach V. L., Hume J. C., Mayes W. F., Powers L. E., Robeson K. A. Committee Reports: Committee on Professional Education: REPORT OF THE CHAIRMAN, 1967. Am J Public Health Nations Health. 1968 Mar;58(3):573–575. doi: 10.2105/ajph.58.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sugawara M., Hagen G. A. Ectopic ACTH syndrome due to salivary gland adenoid cystic carcinoma. Arch Intern Med. 1977 Jan;137(1):102–105. [PubMed] [Google Scholar]
  40. Tapia F. J., Polak J. M., Barbosa A. J., Bloom S. R., Marangos P. J., Dermody C., Pearse A. G. Neuron-specific enolase is produced by neuroendocrine tumours. Lancet. 1981 Apr 11;1(8224):808–811. doi: 10.1016/s0140-6736(81)92682-9. [DOI] [PubMed] [Google Scholar]
  41. Tyrrell J. B., Brooks R. M., Fitzgerald P. A., Cofoid P. B., Forsham P. H., Wilson C. B. Cushing's disease. Selective trans-sphenoidal resection of pituitary microadenomas. N Engl J Med. 1978 Apr 6;298(14):753–758. doi: 10.1056/NEJM197804062981401. [DOI] [PubMed] [Google Scholar]
  42. Welbourn R. B. Current status of the apudomas. Ann Surg. 1977 Jan;185(1):1–12. doi: 10.1097/00000658-197701000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Welbourn R. B., Montgomery D. A., Kennedy T. L. The natural history of treated Cushing's syndrome. Br J Surg. 1971 Jan;58(1):1–16. doi: 10.1002/bjs.1800580102. [DOI] [PubMed] [Google Scholar]
  44. White F. E., White M. C., Drury P. L., Fry I. K., Besser G. M. Value of computed tomography of the abdomen and chest in investigation of Cushing's syndrome. Br Med J (Clin Res Ed) 1982 Mar 13;284(6318):771–774. doi: 10.1136/bmj.284.6318.771. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES