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Early Morning Cortisol Levels as a Predictor of Remission After Transsphenoidal Surgery for Cushing’s Disease

Division of Neurosurgery (F.E., J.R.D., P.M., D.M., D.F.K.), Pituitary Tumor and Neuroendocrine Program (F.E., P.C., D.F.K.), and Division of Endocrinology (P.C.), University of California, Los Angeles (UCLA), School of Medicine, Los Angeles, California 90095; Department of Neurological Sciences (F.E.), Division of Neurosurgery, Università degli Studi di Napoli Federico II, 80131 Naples, Italy; UCLA Gonda Diabetes Center (P.C.), Los Angeles, California 90095; and Division of Endocrinology, Metabolism, and Nutrition (C.W., R.S.S.), Harbor-UCLA Medical Center, Torrance, California 90502

Address all correspondence and requests for reprints to: Daniel F. Kelly, M.D., 200 University of Los Angeles California Medical Plaza, Suite 504, Box 718224, Los Angeles, California 90095-7182. E-mail: dkelly{at}mednet.ucla.edu.

Introduction: We describe the use of serum cortisol and ACTH levels on postoperative d 1 and 2 as remission predictors after transsphenoidal surgery for Cushing’s disease (CD).

Methods: Morning cortisol and ACTH levels were drawn daily after surgery; glucocorticoids were withheld until evidence of hypocortisolemia. Early remission was defined retrospectively as a subnormal morning cortisol level [140 nmol/liter (5 µg/dl)] on postoperative d 1 or 2 and sustained remission as subsequent eucortisolemia.

Results: Of 40 consecutive adults with CD (mean age 39 yr), 80% achieved early remission. Of 39 patients with a minimum follow-up of 14 months (mean 33 months), 31 (79.5%) achieved sustained remission at a mean follow-up of 32 months, including 30 of 31 (97%) with early remission and one of eight (12%) without early remission (P < 0.0001). Sustained remission was achieved in 26 of 28 (93%) patients having their first operation, compared with five of 11 (45%) with a prior unsuccessful operation (P < 0.001). For the 32 patients in early remission vs. the eight in nonremission, mean nadir cortisol levels were 57.6 ± 33.0 (2.05 ± 1.2 µg/dl) vs. 631.1 ± 352.2 nmol/liter (22.9 ± 12.8 µg/dl) (P < 0.0001), and nadir ACTH levels were 11.9 ± 6.5 vs. 64.1 ± 54.6 ng/liter (P < 0.001). Of 31 patients with sustained remission, 100% had subnormal morning cortisol levels, whereas 31% had subnormal ACTH levels (P < 0.0001).

Conclusions: Serum morning cortisol levels on postoperative d 1 and 2 without glucocorticoid replacement provide a safe, simple, and reliable measure of early remission for CD and are predictive of sustained remission. This method allows for consideration of a repeat operation during the same hospitalization in patients with persistent hypercortisolemia.