Post-Operative Cortisol Dynamics and Correlations with Successful Hormonal Remission in ETSS-Treated Cushing's Patients: Implications for Management

Friday, May 3, 2024

Presenting Author(s)

Ishan Shah, BS

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States

Co-Author(s)

Alex Renn, BS

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States

Co-Author(s)

JC

John D. Carmichael, MD

Associate Professor, Clinical Chief
Department of Endocrinology, Keck School of Medicine of USC
Loma Linda, California, United States
Stephanie K. Cheok, MD (she/her/hers)

Assistant Professor
Department of Neurosurgery, Medical College of Wisconsin
Milwaukee, WI, US
Jeffrey J. Feng, MS

Medical Student
Keck School of Medicine of USC
Hacienda Heights, CA, US
Gage A. Guerra, BA

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States
ZK

Zain Kashif, BS

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States, United States
Racheal Peterson, MD

Neurosurgery Fellow
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States
Shreveport, Louisiana, United States
MY

Max Yang, BS

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States
Chino, California, United States
GZ

Gabriel Zada, MD

Professor of Neurological Surgery
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States, United States

Introduction: Cushing's Disease, marked by sustained hypercortisolism due to excess ACTH secretion by the pituitary gland, often necessitates surgical intervention. Endoscopic transsphenoidal surgery (ETSS) is the gold-standard treatment, but prediction of post-operative hormonal remission remains elusive. This study investigates the association between early post-operative cortisol levels and successful remission in ETSS-treated Cushing's patients.

Methods: Fifty-one patients who underwent ETSS for Cushing’s Disease between 2013 and 2023 were retrospectively reviewed for post-operative day (POD) 0-4, or early, nadir cortisol levels, operative details including invasion and tumor type, and follow-up data. Long-term remission was defined as patient eucortisolemia after steroid cessation. Uni- and multi-variate regression was performed to identify associations between surgical parameters and successful hormonal remission. ROC/AUC analysis was used to calculate optimal cut-off patient cortisol levels for prediction of remission.

Results: Of a total of 51 patients, 44 (86.3%) achieved long-term remission after ETSS. A comparison of average early nadir cortisol levels yielded a near-significant decrease within remitted patients (20.6 vs 12.6 μg/dL, p = 0.08). Average cortisol levels by day were lower in the remission group except for POD4, with significant difference observed in POD1 levels (13.0 vs 23.9 μg/dL, p = 0.04). By ROC analysis, nadir cortisol levels < 9.2 μg/dL was predictive of remission the entire cohort over the 4 days (PPV = 95%, AUC = 0.84). Optimal nadir cortisol cut-off thresholds for remission were determined, with values of 16.2 μg/dL (PPV = 100%, AUC = 0.84) for POD1 and 12.4 μg/dL (PPV = 97%, AUC = 0.85) for POD2, thus establishing robust guidelines of nadir cortisol levels associated with hormonal remission.

Conclusion : Early post-operative cortisol levels appear to be a robust predictor of durable biochemical remission in Cushing's patients following ETSS. Prediction of hormonal remission in Cushing’s disease may affect post-operative management and ultimately enhance outcomes in this patient population.