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Published in: Reviews in Endocrine and Metabolic Disorders 2/2010

01-06-2010

Peri-operative management of Cushing’s disease

Authors: Dima AbdelMannan, Warren R. Selman, Baha M. Arafah

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 2/2010

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Abstract

Management of patients with ACTH producing pituitary adenoma remains to be challenging. Removal of the pituitary adenoma through transsphenoidal surgery is the main stay of treatment. Complete resection of the adenoma is followed by the development of ACTH deficiency since the normal corticotrophs are suppressed by the pre-existing hypercortisolemia. The concern for ACTH deficiency has led many centers to advocate the use glucocorticoids before, during and after surgery. We provide evidence that such coverage with glucocorticoids is unnecessary until clinical or biochemical documentation of need is established. Given that patients are closely monitored, they are immediately treated with glucocorticoids once they exhibit any clinical and/or biochemical evidence of adrenal insufficiency. Defining remission in the immediate postoperative period has been rather difficult despite using different biochemical markers. Serum cortisol continues to be the best determinant of disease activity after surgical adenomectomy. However it needs to be interpreted with caution as a biochemical marker of remission in patients given glucocorticoids during and after surgery. Other biochemical markers are also used in the peri-operative period to determine the possibility of remission. These include the dexamethasone suppression test, CRH stimulation without dexamethasone, urinary free cortisol measurements, desmopressin stimulation test, the determination of salivary cortisol and / or plasma ACTH concentrations. Each test has its own advantages and limitations. The simplest and most informative approach is to measure serum cortisol levels repeatedly after surgery without the administration of exogenous glucocorticoids. Low serum cortisol levels (less than 2 ug/dL) in the peri-operative period are highly indicative of surgical success and a high likelihood for clinical remission. Higher serum cortisol levels require careful interpretation and further planning and discussions between the patient and the management team.
Literature
1.
go back to reference Pouratian N, Prevedello DM, Jagannathan J, et al. Outcomes and management of patients with Cushing’s disease without pathological confirmation of tumor resection after transsphenoidal surgery. J Clin Endocrinol Metab. 2007;92:3383–8.CrossRefPubMed Pouratian N, Prevedello DM, Jagannathan J, et al. Outcomes and management of patients with Cushing’s disease without pathological confirmation of tumor resection after transsphenoidal surgery. J Clin Endocrinol Metab. 2007;92:3383–8.CrossRefPubMed
2.
go back to reference Arafah BM, Nasrallah MP. Pituitary tumors: pathophysiology, clinical manifestations and management. Endocr-Relat Cancer. 2001;8:287–305.CrossRefPubMed Arafah BM, Nasrallah MP. Pituitary tumors: pathophysiology, clinical manifestations and management. Endocr-Relat Cancer. 2001;8:287–305.CrossRefPubMed
3.
go back to reference Findling JW, Raff H. Cushing’s syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91:3746–53.CrossRefPubMed Findling JW, Raff H. Cushing’s syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91:3746–53.CrossRefPubMed
4.
go back to reference Boggan JE, Tyrrell JB, Wilson CB. Transsphenoidal microsurgical management of Cushing’s disease. Report of 100 cases. J Neurosurg. 1983;59(2):195–200.CrossRefPubMed Boggan JE, Tyrrell JB, Wilson CB. Transsphenoidal microsurgical management of Cushing’s disease. Report of 100 cases. J Neurosurg. 1983;59(2):195–200.CrossRefPubMed
5.
go back to reference McCance DR, Gordon DS, Fannin TF, Hadden DR, Kennedy L, Sheridan B, et al. Assessment of endocrine function after transsphenoidal surgery for Cushing’s disease. Clin Endocrinol (Oxf). 1993;38(1):79–86.CrossRef McCance DR, Gordon DS, Fannin TF, Hadden DR, Kennedy L, Sheridan B, et al. Assessment of endocrine function after transsphenoidal surgery for Cushing’s disease. Clin Endocrinol (Oxf). 1993;38(1):79–86.CrossRef
6.
go back to reference Lamberts SW, van der Lely AJ, de Herder WW. Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing’s disease. Considerations concerning preoperative medical treatment and the long-term follow-up. J Clin Endocrinol Metab. 1995;80:3111–3.CrossRefPubMed Lamberts SW, van der Lely AJ, de Herder WW. Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing’s disease. Considerations concerning preoperative medical treatment and the long-term follow-up. J Clin Endocrinol Metab. 1995;80:3111–3.CrossRefPubMed
7.
go back to reference Simmons NE, Alden TD, Thorner MO, Laws Jr ER. Serum cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg. 2001;95:1–8.CrossRefPubMed Simmons NE, Alden TD, Thorner MO, Laws Jr ER. Serum cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg. 2001;95:1–8.CrossRefPubMed
8.
go back to reference Yap LB, Turner HE, Adams CB, Wass JA. Undetectable postoperative cortisol does not always predict long-term remission in Cushing’s disease: a single centre audit. Clin Endocrinol (Oxf). 2002;56:25–31.CrossRef Yap LB, Turner HE, Adams CB, Wass JA. Undetectable postoperative cortisol does not always predict long-term remission in Cushing’s disease: a single centre audit. Clin Endocrinol (Oxf). 2002;56:25–31.CrossRef
9.
go back to reference Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, et al. Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab. 2004;89:6348–57.CrossRefPubMed Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, et al. Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab. 2004;89:6348–57.CrossRefPubMed
10.
go back to reference Hoybye C, Grenback E, Thoren M, Hulting AL, Lundblad L, von Holst H, et al. Transsphenoidal surgery in Cushing disease: 10 years of experience in 34 consecutive cases. J Neurosurg. 2004;100:634–8.CrossRefPubMed Hoybye C, Grenback E, Thoren M, Hulting AL, Lundblad L, von Holst H, et al. Transsphenoidal surgery in Cushing disease: 10 years of experience in 34 consecutive cases. J Neurosurg. 2004;100:634–8.CrossRefPubMed
11.
go back to reference Rollin GA, Ferreira NP, Junges M, Gross JL, Czepielewski MA, et al. Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing’s disease. J Clin Endocrinol Metab. 2004;89:1131–9.CrossRefPubMed Rollin GA, Ferreira NP, Junges M, Gross JL, Czepielewski MA, et al. Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing’s disease. J Clin Endocrinol Metab. 2004;89:1131–9.CrossRefPubMed
12.
go back to reference Esposito F, Dusick JR, Cohan P, Moftakhar P, McArthur D, Wang C, et al. Clinical review: early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab. 2006;91:7–13.CrossRefPubMed Esposito F, Dusick JR, Cohan P, Moftakhar P, McArthur D, Wang C, et al. Clinical review: early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab. 2006;91:7–13.CrossRefPubMed
13.
go back to reference Czepielewski MA, Rollin GA, Casagrande A, et al. Criteria of cure and remission in Cushing’s disease: an update. Arq Bras Endocrinol Metabol. 2007;51(8):1362–72. Review.PubMed Czepielewski MA, Rollin GA, Casagrande A, et al. Criteria of cure and remission in Cushing’s disease: an update. Arq Bras Endocrinol Metabol. 2007;51(8):1362–72. Review.PubMed
14.
go back to reference Krikorian A, Abdelmannan D, Selman WR, Arafah BM. Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery. Neurosurg Focus. 2007;23(3):E6–E11.CrossRefPubMed Krikorian A, Abdelmannan D, Selman WR, Arafah BM. Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery. Neurosurg Focus. 2007;23(3):E6–E11.CrossRefPubMed
15.
go back to reference Prevedello DM, Pouratian N, Sherman J, et al. Management of Cushing’s disease: outcome in patients with microadenoma detected on pituitary magnetic resonance imaging. J Neurosurg. 2008;109(4):751–9.CrossRefPubMed Prevedello DM, Pouratian N, Sherman J, et al. Management of Cushing’s disease: outcome in patients with microadenoma detected on pituitary magnetic resonance imaging. J Neurosurg. 2008;109(4):751–9.CrossRefPubMed
16.
go back to reference Nelson DH, Meakin JW, Thorn GW. ACTH-producing pituitary tumors following adrenalectomy for Cushing’s syndrome. Ann Intern Med. 1960;52:560.PubMed Nelson DH, Meakin JW, Thorn GW. ACTH-producing pituitary tumors following adrenalectomy for Cushing’s syndrome. Ann Intern Med. 1960;52:560.PubMed
17.
go back to reference Sonino N, Boscaro M, Fallo F. Pharmacologic management of Cushing syndrome: new targets for therapy. Treat Endocrinol. 2005;4:87–94.CrossRefPubMed Sonino N, Boscaro M, Fallo F. Pharmacologic management of Cushing syndrome: new targets for therapy. Treat Endocrinol. 2005;4:87–94.CrossRefPubMed
18.
go back to reference Stalla GK, Stalla J, Huber M, Loeffler JP, Hollt V, von Werder K, et al. Ketoconazole inhibits corticotropic cell function in vitro. Endocrinology. 1988;122:618–23.CrossRefPubMed Stalla GK, Stalla J, Huber M, Loeffler JP, Hollt V, von Werder K, et al. Ketoconazole inhibits corticotropic cell function in vitro. Endocrinology. 1988;122:618–23.CrossRefPubMed
19.
go back to reference Graham KE, Samuels MH, Raff H, Barnwell SL, Cook DM. Intraoperative adrenocorticotropin levels during transsphenoidal surgery for Cushing’s disease do not predict cure. J Clin Endocrinol Metab. 1997;82:1776–9.CrossRefPubMed Graham KE, Samuels MH, Raff H, Barnwell SL, Cook DM. Intraoperative adrenocorticotropin levels during transsphenoidal surgery for Cushing’s disease do not predict cure. J Clin Endocrinol Metab. 1997;82:1776–9.CrossRefPubMed
20.
go back to reference Arafah BM, Pearson OH. Cushing’s syndrome. In: Rakel RE, editor. Conn’s current therapy. 36th ed. Philadelphia: WB Saunders Co; 1984. p. 472–7. Arafah BM, Pearson OH. Cushing’s syndrome. In: Rakel RE, editor. Conn’s current therapy. 36th ed. Philadelphia: WB Saunders Co; 1984. p. 472–7.
21.
go back to reference Trainer PJ, Lawrie HS, Verhelst J, Howlett TA, Lowe DG, Grossman AB, et al. Transsphenoidal resection in Cushing’s disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf). 1993;38:73–8.CrossRef Trainer PJ, Lawrie HS, Verhelst J, Howlett TA, Lowe DG, Grossman AB, et al. Transsphenoidal resection in Cushing’s disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf). 1993;38:73–8.CrossRef
22.
go back to reference Chee GH, Mathias DB, James RA, Kendall-Taylor P. Transsphenoidal pituitary surgery in Cushing’s disease: can we predict outcome? Clin Endocrinol (Oxf). 2001;54:617–26.CrossRef Chee GH, Mathias DB, James RA, Kendall-Taylor P. Transsphenoidal pituitary surgery in Cushing’s disease: can we predict outcome? Clin Endocrinol (Oxf). 2001;54:617–26.CrossRef
23.
go back to reference Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629–38.CrossRefPubMed Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629–38.CrossRefPubMed
24.
go back to reference Coe CL, Murai JT, Wiener SG, Levine S, Siiteri PK. Rapid cortisol and corticosteroid-binding globulin responses during pregnancy and after estrogen administration in the squirrel monkey. Endocrinology. 1986;118:435–40.CrossRefPubMed Coe CL, Murai JT, Wiener SG, Levine S, Siiteri PK. Rapid cortisol and corticosteroid-binding globulin responses during pregnancy and after estrogen administration in the squirrel monkey. Endocrinology. 1986;118:435–40.CrossRefPubMed
25.
go back to reference Orbach O, Schussler GC. Increased serum cortisol binding in chronic active hepatitis. Am J Med. 1989;86:39–42.CrossRefPubMed Orbach O, Schussler GC. Increased serum cortisol binding in chronic active hepatitis. Am J Med. 1989;86:39–42.CrossRefPubMed
26.
go back to reference Abdelmannan D, Krikorian A, Selman WR, Arafah BM. Measurements of plasma ACTH in the peri-operative period can predict the long-term outcome of surgically-treated patients with ACTH-secreting adenomas (Cushing’s Disease) OR40-6. Proceedings of the 90th Endocrine Society meeting in San Francisco, CA; June 2008. Abdelmannan D, Krikorian A, Selman WR, Arafah BM. Measurements of plasma ACTH in the peri-operative period can predict the long-term outcome of surgically-treated patients with ACTH-secreting adenomas (Cushing’s Disease) OR40-6. Proceedings of the 90th Endocrine Society meeting in San Francisco, CA; June 2008.
27.
go back to reference Chen JC, Amar AP, Choi S, Singer P, Couldwell WT, Weiss MH. Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg. 2003;98(5):967–73.CrossRefPubMed Chen JC, Amar AP, Choi S, Singer P, Couldwell WT, Weiss MH. Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg. 2003;98(5):967–73.CrossRefPubMed
28.
go back to reference Invitti C, Pecori Giraldi F, de Martin M. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic–Pituitary–Adrenal Axis. J Clin Endocrinol Metab. 1999;84(2):440–8.CrossRefPubMed Invitti C, Pecori Giraldi F, de Martin M. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic–Pituitary–Adrenal Axis. J Clin Endocrinol Metab. 1999;84(2):440–8.CrossRefPubMed
29.
go back to reference Banerjee A, Martin N, Dhillo W, Roncaroli F, Meeran K. Use of the dexamethasone-suppressed corticotrophin-releasing hormone test to predict cure in patients with Cushing’s disease following pituitary surgery, in Society for Endocrinology BES. Birmingham, UK, 2007. Banerjee A, Martin N, Dhillo W, Roncaroli F, Meeran K. Use of the dexamethasone-suppressed corticotrophin-releasing hormone test to predict cure in patients with Cushing’s disease following pituitary surgery, in Society for Endocrinology BES. Birmingham, UK, 2007.
30.
go back to reference Newell-Price J, Perry L, Medbak S, et al. A combined test using desmopressin and corticotropin releasing hormone in the differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1997;82:176–81.CrossRefPubMed Newell-Price J, Perry L, Medbak S, et al. A combined test using desmopressin and corticotropin releasing hormone in the differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1997;82:176–81.CrossRefPubMed
31.
go back to reference Malerbi DA, Mendonc BB, Lieberman B, Toledo SPA, Corradini MCM, Cunha-Neto MB, et al. The desmopressin stimulation test in the differential diagnosis of Cushing’s syndrome. Clin Endocrinol. 1993;38:463–72.CrossRef Malerbi DA, Mendonc BB, Lieberman B, Toledo SPA, Corradini MCM, Cunha-Neto MB, et al. The desmopressin stimulation test in the differential diagnosis of Cushing’s syndrome. Clin Endocrinol. 1993;38:463–72.CrossRef
32.
go back to reference Colombo P, Dall’Asta C, Barbetta L, et al. Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing’s disease. Eur J Endocrinol. 2003;143:227–34.CrossRef Colombo P, Dall’Asta C, Barbetta L, et al. Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing’s disease. Eur J Endocrinol. 2003;143:227–34.CrossRef
33.
go back to reference Losa M, Mortini P, Dylgjeri S. Desmopressin stimulation test before and after pituitary surgery in patients with Cushing’s disease. Clin Endocrinol. 2006;55:61–8.CrossRef Losa M, Mortini P, Dylgjeri S. Desmopressin stimulation test before and after pituitary surgery in patients with Cushing’s disease. Clin Endocrinol. 2006;55:61–8.CrossRef
34.
go back to reference Friedman RB, Oldfield EH, Nieman LK, Chrousos GP, Doppman JL, Cutler Jr GB, et al. Repeat transsphenoidal surgery for Cushing’s disease. J Neurosurg. 1989;71:520–7.CrossRefPubMed Friedman RB, Oldfield EH, Nieman LK, Chrousos GP, Doppman JL, Cutler Jr GB, et al. Repeat transsphenoidal surgery for Cushing’s disease. J Neurosurg. 1989;71:520–7.CrossRefPubMed
35.
go back to reference Ram Z, Nieman LK, Cutler Jr GB, Chrousos GP, Doppman JL, Oldfield EH, et al. Early repeat surgery for persistent Cushing’s disease. J Neurosurg. 1994;80:37–45.CrossRefPubMed Ram Z, Nieman LK, Cutler Jr GB, Chrousos GP, Doppman JL, Oldfield EH, et al. Early repeat surgery for persistent Cushing’s disease. J Neurosurg. 1994;80:37–45.CrossRefPubMed
36.
go back to reference Benveniste RJ, King WA, Walsh J, Lee JS, Delman BN, Post KD. Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg. 2005;102:1004–12.CrossRefPubMed Benveniste RJ, King WA, Walsh J, Lee JS, Delman BN, Post KD. Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg. 2005;102:1004–12.CrossRefPubMed
37.
go back to reference Locatelli M, Vance ML, Laws ER. Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab. 2005;90:5478–82.CrossRefPubMed Locatelli M, Vance ML, Laws ER. Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab. 2005;90:5478–82.CrossRefPubMed
Metadata
Title
Peri-operative management of Cushing’s disease
Authors
Dima AbdelMannan
Warren R. Selman
Baha M. Arafah
Publication date
01-06-2010
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 2/2010
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-010-9140-6

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