Question: Is it possible to predict if a pituitary tumor will recur based on levels of cortisol and ACTH following surgery? 

Answer: The general answer is “no,” but studies have looked at this question in a number of ways. If a patient is in remission after transsphenoidal surgery for Cushing’s disease, the postoperative cortisol levels, whether measured as salivary cortisol, 24 hour urine free cortisol, or fasting serum cortisol, should be very low, since the tumor has suppressed the normal ACTH secreting cells in the pituitary and it takes time (typically, 6-12 months) for those cells to recover and begin secreting normal levels of ACTH. One type of study has asked “Is there a postoperative cortisol level below which the risk of recurrence is zero?” A study published in Clinical Endocrinology in 2002 found that even when the postoperative cortisol level was undetectable, 11.5% of the patients developed recurrence within 36 months, suggesting that, even if the normal ACTH secreting cells appear to be completely suppressed, tumor cells may be present and the tumor may recur. A different approach would be to determine if a more stringent criterion for remission was associated with a decreased risk of recurrence. This was addressed by a study which looked at the difference between using a remission criteria of postoperative serum cortisol < 2ug/dl versus < 5ug/dl and found that the overall recurrence rates were similar (9.5% versus 10.4%); although patients with levels between 2 ug/dl and 5 ug/dl seemed to recur more frequently, this difference did not reach significance. Another way to ask the question would be “is there a group of patients who seem to have a higher risk of recurrence?” The answer here is yes, probably, for two groups of patients. Those patients with postoperative cortisol levels in the normal range, as opposed to suppressed levels, appear to have an increased risk of recurrence. The data were reviewed in a recent review, which quoted overall recurrence rates of 9% in patients with low postoperative cortisol levels, as opposed to 24% in patients with normal postoperative cortisol levels. In addition, there is a small group of patients with delayed, as opposed to early (within a few days) fall in postoperative cortisol levels, and these patients also appear to have an increased risk of recurrence.

The bottom line: while an early profound fall in cortisol levels is a good prognostic indicator of success, there is no test that will definitively rule out the possibility of future recurrence, and all patients with Cushing’s disease need to be followed closely even after successful surgery.

i) Yap LB; Turner HE; Adams CB; Wass JA, Clinical Endocrinology 2002 Jan; Vol. 56 (1), pp. 25-31
ii) Lindsay JR; Oldfield EH; Stratakis CA; Nieman LK, The Journal Of Clinical Endocrinology And Metabolism 2011 Jul; Vol. 96 (7), pp. 2057-64
iii) Sughrue ME; Shah JK; Devin JK; Kunwar S; Blevins LS Jr, Neurosurgery 2010 Sep; Vol. 67 (3), pp. 688-95.
iv) Valassi E; Biller BM; Swearingen B; Pecori Giraldi F; Losa M; Mortini P; Hayden D; Cavagnini F; Klibanski A, The Journal Of Clinical Endocrinology And Metabolism 2010 Feb; Vol. 95 (2), pp. 601-10

By Dr. Brooke Swearingen, Neurosurgeon, Massachusetts General Hospital, Boston, MA (Winter, 2015)