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Overview of the treatment of Cushing's syndrome

INTRODUCTION

The hypercortisolemia in Cushing's syndrome is usually due to a corticotropin (ACTH)-producing pituitary tumor (Cushing's disease), ectopic ACTH secretion by a nonpituitary tumor, or cortisol secretion by an adrenal adenoma or carcinoma. There are also very rare tumors that secrete corticotropin-releasing hormone (CRH) ectopically, and occasional cases are caused by cortisol secretion by ACTH-independent macronodular or micronodular hyperplasia of the adrenal cortex.

Treatment should be directed, whenever possible, at the primary cause of the syndrome. It is therefore dependent upon accurate differential diagnosis [1]. (See "Establishing the cause of Cushing's syndrome".)

This topic provides an overview of the various therapeutic options available in the treatment of Cushing's syndrome. A detailed review of therapy for Cushing's disease and primary adrenal causes of hypercortisolism is presented separately.

GENERAL PRINCIPLES

Ideal therapy of Cushing's syndrome would achieve the following goals [1,2]:

  • Reverse the clinical manifestations by reducing cortisol secretion to normal
  • Eradicate any tumor threatening the health of the patient
  • Avoid permanent dependence upon medications
  • Avoid permanent hormone deficiency

                 

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Literature review current through: Apr 2012. | This topic last updated: Mar 23, 2011.
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References
Top
  1. Orth DN. Cushing's syndrome. N Engl J Med 1995; 332:791.
  2. Orth DN, Liddle GW. Results of treatment in 108 patients with Cushing's syndrome. N Engl J Med 1971; 285:243.
  3. Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2008; 93:2454.
  4. Chow JT, Thompson GB, Grant CS, et al. Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience. Clin Endocrinol (Oxf) 2008; 68:513.
  5. Kaltsas GA, Mukherjee JJ, Plowman PN, et al. The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors. J Clin Endocrinol Metab 1998; 83:4233.
  6. Aniszewski JP, Young WF Jr, Thompson GB, et al. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg 2001; 25:934.
  7. Ilias I, Torpy DJ, Pacak K, et al. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab 2005; 90:4955.
  8. Isidori AM, Kaltsas GA, Pozza C, et al. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab 2006; 91:371.
  9. Miller CA, Ellison EC. Therapeutic alternatives in metastatic neuroendocrine tumors. Surg Oncol Clin N Am 1998; 7:863.
  10. Lehnert T. Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients. Transplantation 1998; 66:1307.
  11. Tabarin A, Catargi B, Chanson P, et al. Pseudo-tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases. Clin Endocrinol (Oxf) 1995; 42:207.
  12. Nieman LK, Chrousos GP, Kellner C, et al. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. J Clin Endocrinol Metab 1985; 61:536.
  13. von Werder K, Muller OA, Stalla GK. Somatostatin analogs in ectopic corticotropin production. Metabolism 1996; 45:129.
  14. Bertagna X, Favrod-Coune C, Escourolle H, et al. Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide. J Clin Endocrinol Metab 1989; 68:988.
  15. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20:716.
  16. Oberg K. Established clinical use of octreotide and lanreotide in oncology. Chemotherapy 2001; 47 Suppl 2:40.
  17. Ur E, Grossman A. Corticotropin-releasing hormone in health and disease: an update. Acta Endocrinol (Copenh) 1992; 127:193.
  18. Luton JP, Cerdas S, Billaud L, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 1990; 322:1195.
  19. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 1993; 72:3145.
  20. Bodie B, Novick AC, Pontes JE, et al. The Cleveland Clinic experience with adrenal cortical carcinoma. J Urol 1989; 141:257.
  21. Pommier RF, Brennan MF. An eleven-year experience with adrenocortical carcinoma. Surgery 1992; 112:963.
  22. Sarlis NJ, Chrousos GP, Doppman JL, et al. Primary pigmented nodular adrenocortical disease: reevaluation of a patient with carney complex 27 years after unilateral adrenalectomy. J Clin Endocrinol Metab 1997; 82:1274.
  23. Porpiglia F, Fiori C, Bovio S, et al. Bilateral adrenalectomy for Cushing's syndrome: a comparison between laparoscopy and open surgery. J Endocrinol Invest 2004; 27:654.
  24. Malchoff, CD, MacGillvray, D, Malchoff, DM. Adrenocortical hormone-independent adrenal hyperplasia. Endocrinologist 1996; 6:79.
  25. Ogura M, Kusaka I, Nagasaka S, et al. Unilateral adrenalectomy improves insulin resistance and diabetes mellitus in a patient with ACTH-independent macronodular adrenal hyperplasia. Endocr J 2003; 50:715.
  26. Lamas C, Alfaro JJ, Lucas T, et al. Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases. Eur J Endocrinol 2002; 146:237.
  27. Lacroix A, Hamet P, Boutin JM. Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome. N Engl J Med 1999; 341:1577.
  28. Lacroix A, Tremblay J, Rousseau G, et al. Propranolol therapy for ectopic beta-adrenergic receptors in adrenal Cushing's syndrome. N Engl J Med 1997; 337:1429.
  29. Lufkin EG, Wahner HW, Bergstralh EJ. Reversibility of steroid-induced osteoporosis. Am J Med 1988; 85:887.
  30. Hermus AR, Smals AG, Swinkels LM, et al. Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab 1995; 80:2859.
  31. Di Somma C, Pivonello R, Loche S, et al. Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing's disease: a prospective study. Clin Endocrinol (Oxf) 2003; 58:302.
  32. Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: summary of a workshop. J Clin Endocrinol Metab 2001; 86:5681.
  33. Lindsay JR, Nansel T, Baid S, et al. Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab 2006; 91:447.
  34. Dorn LD, Burgess ES, Friedman TC, et al. The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 1997; 82:912.
  35. Bourdeau I, Bard C, Noël B, et al. Loss of brain volume in endogenous Cushing's syndrome and its reversibility after correction of hypercortisolism. J Clin Endocrinol Metab 2002; 87:1949.
  36. Forget H, Lacroix A, Cohen H. Persistent cognitive impairment following surgical treatment of Cushing's syndrome. Psychoneuroendocrinology 2002; 27:367.
  37. Merke DP, Giedd JN, Keil MF, et al. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab 2005; 90:2531.
  38. Devoe DJ, Miller WL, Conte FA, et al. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab 1997; 82:3196.
  39. PLOTZ CM, KNOWLTON AI, RAGAN C. The natural history of Cushing's syndrome. Am J Med 1952; 13:597.
  40. Jäger F, Jäger E, Heintz A, Junginger T. Synchronous bilateral endoscopic adrenalectomy: experiences after 18 operations. Surg Endosc 2004; 18:314.
  41. Anthony LB, Greco FA. Pneumocystis carinii pneumonia: a complication of Cushing's syndrome. Ann Intern Med 1981; 94:488.
  42. Graham BS, Tucker WS Jr. Opportunistic infections in endogenous Cushing's syndrome. Ann Intern Med 1984; 101:334.
  43. Sarlis NJ, Chanock SJ, Nieman LK. Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J Clin Endocrinol Metab 2000; 85:42.
  44. Van Zaane B, Nur E, Squizzato A, et al. Hypercoagulable state in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab 2009; 94:2743.