Postoperative ACTH, cortisol levels may predict Cushing’s disease remission rate

Early and midterm nonremission after transsphenoidal surgery in people with Cushing’s disease may be predicted by normalized early postoperative values for adrenocorticotropic hormone and cortisol, study data show.

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Prashant Chittiboina, MD, MPH, assistant clinical investigator in the neurosurgery unit for pituitary and inheritable diseases at the National Institute of Neurological Diseases and Stroke at the NIH, and colleagues evaluated 250 patients with Cushing’s disease who received 291 transsphenoidal surgery procedures during the study period to determine remission after the procedure. Patients were treated between December 2003 and July 2016. Early remission was assessed at 10 days and medium-term remission was assessed at 11 months.

Early nonremission was predicted by normalized early postoperative values for cortisol (P = .016) and by normalized early postoperative values for adrenocorticotropic hormone (ACTH; P = .048). Early nonremission was further predicted with 100% sensitivity, 39% specificity, 100% negative predictive value and 18% positive predictive value for a cutoff of –12 µg/mL in normalized early postoperative values for cortisol and with 88% sensitivity, 41% specificity, 96% negative predictive value and 16% positive predictive value for a cutoff of –40 pg/mL in normalized early postoperative values for ACTH.

Medium-term nonremission was also predicted by normalized early postoperative values for cortisol (P = .023) and ACTH (P = .025).

“We evaluated the utility of early postoperative cortisol and ACTH levels for predicting nonremission after transsphenoidal adenomectomy for Cushing’s disease,” the researchers wrote. “Postoperative operative day 1 values at 6 a.m. performed best at predicting early nonremission, albeit with a lower [area under the receiver operating characteristic curve]. Normalizing early cortisol and ACTH values to post-[corticotropin-releasing hormone] values improved their prognostic value. Further prospective studies will explore the utility of normalized very early postoperative day 0 cortisol and ACTH levels in identifying patients at risk for nonremission following [transsphenoidal surgery] in patients with [Cushing’s disease].” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

Perspective

PERSPECTIVE

Maria Fleseriu

Diagnosing persistent or recurrent Cushing’s disease is perhaps even more challenging than the initial Cushing’s disease diagnosis. To date, no consensus has been established as the search for reliable outcome predictors of Cushing’s disease remission is somewhat impeded by the rarity of Cushing’s disease and the relatively small number of patients at any single center. Several groups have recommended serial measurement of serum cortisol and ACTH immediately after transsphenoidal surgery to identify patients with persistent Cushing’s disease, especially as some of them might benefit of immediate reoperation. Subnormal or undetectable levels of serum cortisol in the immediate postoperative period have been suggested as predictive of long-term remission; however, this has not been confirmed in subsequent studies. Other investigators have suggested that normalization of 24- hour urine-free cortisol, normalization of circadian rhythm, suppressibility to dexamethasone corticotropin-releasing hormone tests or ACTH stimulation tests could be used to determine remission. The authors of this manuscript, which analyzes one of the largest single-center cohort of patients with Cushing’s disease, hypothesized that the stress induced by transsphenoidal surgery presents an opportunity to analyze postop day 1 results similar to a corticotropin-releasing hormone stimulation test to predict remission from Cushing’s disease. The authors also introduced a novel possible marker, normalized early postoperative values, calculated as immediate postoperative cortisol or ACTH minus preoperative post-corticotropin-releasing hormone stimulation test levels. Serum cortisol and ACTH levels were routinely obtained at 6-hour intervals from postop through day 3 and similar with other studies, postop day 1 cortisol values at 6 a.m. performed best at predicting early nonremission, but normalized early postoperative values improved the prognostic value. The limitations of this study, including absence of long-term data and immediate postop cortisol values in many patients are well acknowledged by the authors. Prospective studies in other centers will explore the utility of normalized early postoperative values cortisol and ACTH in identifying patients at risk for nonremission following transsphenoidal surgery in patients with Cushing’s disease.

Maria Fleseriu, MD, FACE
Professor of Medicine and Neurological Surgery, Oregon Health & Science University, Portland

Disclosure: Fleseriu reports no relevant financial disclosures.

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Source:

Asuzu D, et al. J Clin Endocrinol Metab. 2017;doi:10.1210/jc.2016-3908.