Utility of the Immediate Postoperative Cortisol Concentrations in Patients With Cushing's Disease

BACKGROUNDSeveral investigators have recommended serial measurements of serum cortisol in the days following pituitary surgery to identify patients at risk of recurrence. OBJECTIVEWe systematically reviewed the literature on this topic and analyzed the usefulness of this test in our own patient population. METHODSWe identified studies publishing data regarding recurrence rates after transsphenoidal surgery for Cushing's disease, focusing on studies with data regarding patients with early postoperative cortisol levels. We determined a cumulative relative risk of having a subnormal vs normal cortisol level postoperatively using a fixed-effects meta-analysis model. Additionally, we analyzed our own patients with Cushing's disease undergoing transsphenoidal surgery and performed Kaplan-Meier analysis of recurrence-free survival for patients with undetectable, subnormal but detectable, and normal immediate 8 AM serum cortisol levels. RESULTSFourteen studies met inclusion criteria. The length of follow-up varied between 32 and 115 months. The cumulative rate of recurrence in the group of patients with subnormal cortisol levels was 9% (95% confidence interval: 6%–12%). The cumulative rate of recurrence in the group with normal cortisol levels was 24% (95% confidence interval: 17%–31%). We analyzed 73 of our own patients and found similar recurrence rates in patients with subnormal vs normal early postoperative cortisol levels (4% vs 22%, χ2 test, P < .05). CONCLUSIONAlthough a subnormal early postoperative cortisol level is predictive of improved outcome after transsphenoidal surgery for Cushing's disease, it is not analogous with cure, nor is a normal level completely predictive of future failure.

[1]  A. Klibanski,et al.  Delayed remission after transsphenoidal surgery in patients with Cushing's disease. , 2010, The Journal of clinical endocrinology and metabolism.

[2]  J. Bertherat,et al.  Midnight salivary cortisol determination for assessing the outcome of transsphenoidal surgery in Cushing's disease. , 2008, The Journal of clinical endocrinology and metabolism.

[3]  W. Selman,et al.  Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery. , 2007, Neurosurgical focus.

[4]  F. Esposito,et al.  Clinical review: Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. , 2006, Journal of Clinical Endocrinology and Metabolism.

[5]  D. McCance,et al.  Long‐term remission rates after pituitary surgery for Cushing's disease: the need for long‐term surveillance , 2005, Clinical endocrinology.

[6]  E. Laws,et al.  Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing's disease. , 2005, The Journal of clinical endocrinology and metabolism.

[7]  Charles B. Wilson,et al.  Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. , 2004, The Journal of clinical endocrinology and metabolism.

[8]  J. Gross,et al.  Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease. , 2004, The Journal of clinical endocrinology and metabolism.

[9]  J. Romijn,et al.  Long-term predictive value of postsurgical cortisol concentrations for cure and risk of recurrence in Cushing's disease. , 2003, The Journal of clinical endocrinology and metabolism.

[10]  D. Rees,et al.  Long‐term follow‐up results of transsphenoidal surgery for Cushing’s disease in a single centre using strict criteria for remission , 2002, Clinical endocrinology.

[11]  J. Wass,et al.  Undetectable postoperative cortisol does not always predict long‐term remission in Cushing’s disease: a single centre audit * , 2002, Clinical endocrinology.

[12]  C. Lamas,et al.  The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing's disease. , 2001, The Journal of clinical endocrinology and metabolism.

[13]  G. Tindall,et al.  Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. , 1998, The Journal of clinical endocrinology and metabolism.

[14]  M. Buchfelder,et al.  Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery: a retrospective study by the European Cushing's Disease Survey Group. , 1995, The Journal of clinical endocrinology and metabolism.

[15]  P. Loi,et al.  Early postoperative evaluation in patients with Cushing's disease: usefulness of ovine corticotropin-releasing hormone test in the prediction of recurrence of disease. , 1994, European journal of endocrinology.

[16]  J. Doppman,et al.  Early repeat surgery for persistent Cushing's disease. , 1994, Journal of neurosurgery.

[17]  M. McCarthy,et al.  Predicting relapse after transsphenoidal surgery for Cushing's disease. , 1993, The Journal of clinical endocrinology and metabolism.

[18]  D. Lowe,et al.  Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successfuI treatment , 1993, Clinical endocrinology.

[19]  D. Hadden,et al.  Assessment of endocrine function after transsphenoidal surgery for Cushing's disease , 1993, Clinical endocrinology.

[20]  M. Esiri,et al.  TRANSSPHENOIDAL SURGERY FOR CUSHING'S DISEASE: DOES WHAT IS REMOVED DETERMINE THE ENDOCRINE OUTCOME? , 1990, Clinical endocrinology.

[21]  J. Doppman,et al.  Repeat transsphenoidal surgery for Cushing's disease. , 1989, Journal of neurosurgery.

[22]  P. Carpenter,et al.  Transsphenoidal removal of pituitary microadenoma in Cushing's disease. , 1978, Mayo Clinic proceedings.