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Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease.

ABSTRACT: CONTEXT:Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing's disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE:We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS:A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5??g/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS:Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ?5??g/dL and 6% of cases with cortisol nadir ?2??g/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3??g/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ?18.5??g/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ?5?µg/dL before 15?h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ?2?µg/dL, when achieved before 21?h, improved sensitivity to 100%. CONCLUSIONS:In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ?2?µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.

SUBMITTER: Ironside N

PROVIDER: S-EPMC5812811 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease.

Ironside Natasha N Chatain Gregoire G Asuzu David D Benzo Sarah S Lodish Maya M Sharma Susmeeta S Nieman Lynnette L Stratakis Constantine A CA Lonser Russell R RR Chittiboina Prashant P

European journal of endocrinology 20180112 3

<h4>Context</h4>Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing's disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur.<h4>Objective</h4>We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS.<h4>Methods</h4>A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early bioc ...[more]

PMID: 29330227

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Project description:PurposeCushing's disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors.MethodsWe enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010-2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke's cell adenomas.ResultsWe recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing's disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20-40 years of age vs. 50-60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225 vs. n = 52), at similar age (mean 42.94; median 40 vs. mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp's scale grades (p = 0.0147*), smaller preoperative tumors' volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dl vs. 10.47 µg/dl; median 2.49 µg/dl vs. 6.52 µg/dl; p = 0.0028**).ConclusionsOur study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.

Project description:Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD. Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure -Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively. Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ? 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype. Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

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Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease.

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Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease.

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