Normalized Early Postoperative Cortisol and ACTH Values Predict Nonremission After Surgery for Cushing Disease.
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ABSTRACT: Context
Perioperative increases in adrenocorticotropic hormone (ACTH) and cortisol mimic results of corticotropin-releasing hormone (CRH) stimulation testing. This phenomenon may help identify patients with residual adenoma after transsphenoidal surgery (TSS) for Cushing disease (CD).Objective
To predict nonremission after TSS for CD.Design
Retrospective case-control study of patients treated at a single center from December 2003 until July 2016. Early and medium-term remission were assessed at 10 days and 11 months.Patients and setting
Two hundred and ninety-one consecutive TSS cases from 257 patients with biochemical evidence of CD seen at a clinical center.Interventions
Normalized early postoperative values (NEPVs) for cortisol and ACTH were calculated as immediate postoperative cortisol or ACTH levels minus preoperative post-CRH-stimulation test levels.Main outcome measures
Prediction of early nonremission was evaluated using logistic regression. Prediction of medium-term remission was assessed using Cox regression. Predictive ability was quantified by area under the receiver operating characteristic curve (AUROC).Results
NEPVs for cortisol and ACTH predicted early nonremission [adjusted odds ratio (OR): 1.1; 95% confidence interval (CI): 1.0, 1.1; P = 0.016 and adjusted OR: 1.0; 95% CI: 1.0, 1.0; P = 0.048, respectively]. AUROC for NEPV of cortisol was 0.78 (95% CI: 0.61, 0.95); for NEPV of ACTH, it was 0.80 (95% CI: 0.61, 0.98). NEPVs for cortisol and ACTH predicted medium-term nonremission [hazard ratio (HR): 1.1; 95% CI: 1.0, 1.1; P = 0.023 and HR: 1.0; 95% CI: 1.0, 1.0; P = 0.025, respectively].Conclusions
NEPVs for cortisol and ACTH predicted nonremission after TSS for CD.
SUBMITTER: Asuzu D
PROVIDER: S-EPMC6283430 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Postoperative testing after transsphenoidal surgery (TSS) for Cushing disease (CD) in children and its usefulness in predicting residual disease or recurrence are not well studied.The objective of the study was to identify which one of three tests that are routinely performed in our institution after TSS performs better in the identification of noncured patients or predict relapse for CD.This was a retrospective review of clinical data of 72 children who received surgery for CD (age range 5.8-18.3 yr).The study was conducted at a tertiary care center.After TSS, plasma ACTH and serum cortisol (at 0800 h), urinary free cortisol (UFC) values and an ovine CRH (oCRH) stimulation test were obtained. Patients were followed up for 24-120 months by a formal protocol.Of 72 children with CD, 66 (94%) achieved sustained remission after TSS. Two children had persistent disease after TSS, whereas four children appeared cured at first but relapsed later. All four had low or undetectable UFCs that were not different from cured patients (P > 0.0.1). Children who remained in remission had significantly lower morning ACTH and cortisol levels after TSS compared with those who relapsed (P < 0.001). During an oCRH stimulation test, ACTH and cortisol values were higher in patients who relapsed vs. those in remission (P <0.001). Lack of histological confirmation of an adenoma, normal serum cortisol or ACTH, a normal response to oCRH, and glucocorticoid replacement for less than 6 months after surgery were associated with relapse.In pediatric patients with CD, low UFCs after TSS are not good predictors of sustained remission; morning ACTH and cortisol values and/or an oCRH test after TSS predicted patients that recurred.
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Project description:ObjectiveDiagnostic workup of Cushing disease (CD) involves imaging evaluation of the pituitary gland, but in many patients no tumour is visualised. The aim of this study is to describe the association of magnetic resonance imaging (MRI) findings with the postoperative course of paediatric and adolescent patients with CD.PatientsPatients with a diagnosis of CD at less than 21 years of age with MRI evaluation of the pituitary before first transsphenoidal surgery were included.MeasurementsClinical, imaging and biochemical data were analysed.ResultsOne hundred and eighty-six patients with paediatric or adolescent-onset CD were included in the study. Of all patients, 127 (68.3%) had MRI findings consistent with pituitary adenoma, while the remaining had negative or inconclusive MRI. Patients with negative MRI were younger in age and had lower morning cortisol and adrenocorticotropin levels. Of 181 patients with data on postoperative course, patients with negative MRI had higher odds of not achieving remission after the first surgery (odds ratio = 2.6, 95% confidence intervals [CIs] = 1.1-6.0) compared to those with positive MRI. In patients with remission after first transsphenoidal surgery, long-term recurrence risk was not associated with the detection of a pituitary adenoma in the preoperative MRI (hazard risk = 2.1, 95% CI = 0.7-5.8).ConclusionsUp to one-third of paediatric and adolescent patients with CD do not have a pituitary tumour visualised in MRI. A negative MRI is associated with higher odds of nonremission after surgery; however, if remission is achieved, long-term risk for recurrence is not associated with the preoperative MRI findings.
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Project description:PurposeHair cortisol evaluation has been used to help detect patients with suspected Cushing syndrome. Our goal was to correlate segmental hair cortisol with biochemical testing in patients with Cushing syndrome and controls. This study was a prospective analysis of hair cortisol in confirmed Cushing syndrome cases over 16 months.MethodsThirty-six subjects (26.5 ± 18.9 years, 75% female, and 75% Caucasian) were analyzed by diurnal serum cortisol, 24 h urinary free cortisol corrected for body surface area (UFC/BSA), and 24 h urinary 17-hydroxysteroids corrected for creatinine (17OHS/Cr). Thirty patients were diagnosed with Cushing syndrome, and six were defined as controls. 3-cm hair samples nearest to the scalp, cut into 1-cm segments (proximal, medial, and distal), were analyzed for cortisol by enzyme immunoassay and measured as pmol cortisol/g dry hair. Hair cortisol levels were compared with laboratory testing done within previous 2 months of the evaluation.ResultsProximal hair cortisol was higher in Cushing syndrome patients (266.6 ± 738.4 pmol/g) than control patients (38.9 ± 25.3 pmol/g) (p = 0.003). Proximal hair cortisol was highest of all segments in 25/36 (69%) patients. Among all subjects, proximal hair cortisol was strongly correlated with UFC/BSA (r = 0.5, p = 0.005), midnight serum cortisol (r = 0.4, p = 0.03), and 17OHS/Cr, which trended towards significance (r = 0.3, p = 0.06).ConclusionsAmong the three examined hair segments, proximal hair contained the highest cortisol levels and correlated the most with the initial biochemical tests for Cushing syndrome in our study. Further studies are needed to validate proximal hair cortisol in the diagnostic workup for Cushing syndrome.
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Project description:BackgroundThe aim of this study was to compare morning surgery (Group A), characterized by high cortisol levels, with afternoon surgery (Group B), characterized by low cortisol levels, with respect to cortisol, inflammatory cytokines (interleukin [IL]-6, IL-8), and postoperative hospital days (POHD) after hip surgery.MethodsThe study was conducted in a single center, prospective, randomized (1:1) parallel group trial. Patients undergoing total hip replacement or hemiarthroplasty were randomly divided into two groups according to the surgery start time: 8 AM (Group A) or 1-2 PM (Group B). Cortisol and cytokine levels were measured at 7:30 AM on the day of surgery, before induction of anesthesia, and at 6, 12, 24, and 48 hours (h) after surgery. Visual analogue scale (VAS) and POHD were used to evaluate the clinical effect of surgery start time. VAS was measured at 6, 12, 24, and 48 h postoperatively, and POHD was measured at discharge.ResultsIn total, 44 patients completed the trial. The postoperative cortisol level was significantly different between the two groups. (24 h, P < .001; 48 h, P < .001). The percentage of patients whose level returned to the initial level was higher in Group B than in Group A (P < .001). Significant differences in IL-6 levels were observed between the two groups at 12, 24, and 48 h after surgery (P = .015; P = .005; P = .002), and in IL-8 levels at 12 and 24 h after surgery (P = .002, P < .001). There was no significant difference between the two groups in VAS and POHD. However, only three patients in Group A were inpatients for more than 3 weeks (P = .233).ConclusionsAfternoon surgery allowed for more rapid recovery of cortisol to the baseline level than morning surgery, and IL-6 and IL-8 were lower at 1-2 days postoperatively. The results of this study suggest that afternoon surgery may be considered in patients with postoperative delayed wound healing or inflammation because of the difference in cortisol, IL-6 and 8 in according to surgery start time.Clinical trial registration numberNCT03076827 (ClinicalTRrial.gov).
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Project description:INTRODUCTION:The diagnosis of endogenous Cushing syndrome is often challenging and requires multiple repeated blood, urine, and saliva tests to detect elevated cortisol levels. Hair cortisol concentration has been described as a marker of long-term exposure to systemic cortisol in patients with Cushing syndrome. Like hemoglobin A1c is used to detect serum glucose exposure over months, segmental hair cortisol can help identify patients with milder forms of and/or periodic or cyclical Cushing syndrome, which may reduce time and costs associated with collection of urine, salivary, and serum cortisol. AREAS COVERED:Success of hair cortisol in detection of Cushing syndrome will be discussed in context of current literature, including differences between total or segmental hair cortisol in accurately determining timeline of cortisol exposure. Optimal methods of hair collection, storage, processing, and analysis and efforts toward standardization will be a major focus. EXPERT COMMENTARY:Recent evidence suggests increased sensitivity and specificity of hair cortisol in detecting Cushing syndrome. Future guidelines should consider this test as a routine part of the repertoire of screening tests for Cushing syndrome. Possible confounders to explain discrepant results in the literature will be discussed.
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Project description:BackgroundSepsis is typically hallmarked by high plasma (free) cortisol and suppressed cortisol breakdown, while plasma adrenocorticotropic hormone (ACTH) is not increased, referred to as 'ACTH-cortisol dissociation.' We hypothesized that sepsis acutely activates the hypothalamus to generate, via corticotropin-releasing hormone (CRH) and vasopressin (AVP), ACTH-induced hypercortisolemia. Thereafter, via increased availability of free cortisol, of which breakdown is reduced, feedback inhibition at the pituitary level interferes with normal processing of pro-opiomelanocortin (POMC) into ACTH, explaining the ACTH-cortisol dissociation. We further hypothesized that, in this constellation, POMC leaches into the circulation and can contribute to adrenocortical steroidogenesis.MethodsIn two human studies of acute (ICU admission to day 7, N = 71) and prolonged (from ICU day 7 until recovery; N = 65) sepsis-induced critical illness, POMC plasma concentrations were quantified in relation to plasma ACTH and cortisol. In a mouse study of acute (1 day), subacute (3 and 5 days) and prolonged (7 days) fluid-resuscitated, antibiotic-treated sepsis (N = 123), we further documented alterations in hypothalamic CRH and AVP, plasma and pituitary POMC and its glucocorticoid-receptor-regulated processing into ACTH, as well as adrenal cortex integrity and steroidogenesis markers.ResultsThe two human studies revealed several-fold elevated plasma concentrations of the ACTH precursor POMC from the acute to the prolonged phase of sepsis and upon recovery (all p < 0.0001), coinciding with the known ACTH-cortisol dissociation. Elevated plasma POMC and ACTH-corticosterone dissociation were confirmed in the mouse model. In mice, sepsis acutely increased hypothalamic mRNA of CRH (p = 0.04) and AVP (p = 0.03) which subsequently normalized. From 3 days onward, pituitary expression of CRH receptor and AVP receptor was increased. From acute throughout prolonged sepsis, pituitary POMC mRNA was always elevated (all p < 0.05). In contrast, markers of POMC processing into ACTH and of ACTH secretion, negatively regulated by glucocorticoid receptor ligand binding, were suppressed at all time points (all p ≤ 0.05). Distorted adrenocortical structure (p < 0.05) and lipid depletion (p < 0.05) were present, while most markers of adrenocortical steroidogenic activity were increased at all time points (all p < 0.05).ConclusionTogether, these findings suggest that increased circulating POMC, through CRH/AVP-driven POMC expression and impaired processing into ACTH, could represent a new piece in the puzzling ACTH-cortisol dissociation.
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Project description:The Centers for Medicare and Medicaid Services have implemented penalties for hospitals with above-average readmission rates under the Hospital Readmissions Reductions Program. These changes will likely be extended to affect postoperative readmissions in the future.To identify variables that place patients at risk for readmission, develop a predictive nomogram, and validate this nomogram.Retrospective review and prospective validation of a predictive nomogram. A predictive nomogram was developed with the linear predictor method using the American College of Surgeons National Surgical Quality Improvement Program database paired with institutional billing data for patients who underwent nonemergent inpatient general surgery procedures. The nomogram was developed from August 1, 2006, through December 31, 2011, in 2799 patients and prospectively validated from November 1, 2013, through December 19, 2013, in 255 patients at a single academic institution. Area under the curve and positive and negative predictive values were calculated.The outcome of interest was readmission within 30 days of discharge following an index hospitalization for a surgical procedure.Bleeding disorder (odds ratio, 2.549; 95% CI, 1.464-4.440), long operative time (odds ratio, 1.601; 95% CI, 1.186-2.160), in-hospital complications (odds ratio, 16.273; 95% CI, 12.028-22.016), dependent functional status, and the need for a higher level of care at discharge (odds ratio, 1.937; 95% CI, 1.176-3.190) were independently associated with readmission. The nomogram accurately predicted readmission (C statistic?=?0.756) in a prospective evaluation. The negative predictive value was 97.9% in the prospective validation, while the positive predictive value was 11.1%.Development of an online calculator using this predictive model will allow us to identify patients who are at high risk for readmission at the time of discharge. Patients with increased risk may benefit from more intensive postoperative follow-up in the outpatient setting.
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Project description:Objectiveto determine whether incident postoperative delirium in elective older surgical patient was associated with increased risk for mortality, controlling for covariates of 5-year mortality.Designsecondary analysis of prospective cohort studies.Settingacademic Medical Center.Subjectspatients ≥65 years of age undergoing elective non-cardiac surgery.Outcomespostoperative assessments of delirium measured using the Confusion Assessment Method (CAM), mortality within 5 years of the index surgery was determined from National Death Index records.Resultspostoperative delirium occurred in 332/1,315 patients (25%). Five years after surgery, 175 patients (13.3%) were deceased. Older age was associated with an increased odds of mortality [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.20-2.70] for those aged 70-79 years compared to those aged <70 years, and OR 3.29, 95% CI 2.14-5.06 for those aged >80 years. Other variables associated with 5-year mortality on bi-variate analyses were white race, self-rated functional status, lower preoperative cognitive status, higher risk score as measured by the American Society of Anesthesiologists (ASA) classification, higher surgical risk score, history of congestive heart failure, myocardial infarction, renal disease, cancer, peripheral vascular disease and postoperative delirium. However, postoperative delirium was not associated with 5-year mortality on multi-variate logistic regression (OR 1.18, 95% CI 0.85-1.65).Conclusionsour results showed that delirium was not associated with 5-year mortality in elective surgical patients after consideration of co-variates of mortality. Our results suggest the importance of accounting for known preoperative risks for mortality when investigating the relationship between delirium and long-term mortality.
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Project description:BackgroundAppropriate sizing of the implantable collamer lens (ICL) and accurate prediction of the vault are crucial prior to surgery. However, sometimes, the vault value is higher or lower than predicted, necessitating reoperation. The present study aimed to develop neural networks for improving predictions of vault values following ICL implantation based on preoperative biometric data.MethodsThis retrospective study included 137 eyes of 74 patients with ICLs. Linear regression and neural network analyses were used to examine the relationship between vault values at the 6-month follow-up and preoperative parameters (e.g., ICL characteristics and biometrics).ResultsLinear regression analysis revealed that vault values were correlated with five variables: ICL size, anterior chamber depth (ACD), angle-to-angle (ATA), white-to-white (WTW), and lens thickness (LT) (adjusted R2 = 0.411). Inclusion of more input variables was associated with better performance in the neural network analysis. The degree of fit when all 11 variables were included in the neural network model was close to 1 (R2 = 0.98). R2 values for the quaternary neural network model enrolling four input variables (ICL size, ATA, ACD, and LT) reached 0.90.ConclusionsA neural network equation including the ICL size and biometric parameters of the anterior segment (ATA, ACD, and LT) can be used to predict the postoperative vault, aiding in the selection of an appropriate ICL size and reducing the need for reoperation after surgery.
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Project description:Opioids play a critical role in acute postoperative pain management. Our objective was to develop machine learning models to predict postoperative opioid requirements in patients undergoing ambulatory surgery. To develop the models, we used a perioperative dataset of 13,700 patients (? 18 years) undergoing ambulatory surgery between the years 2016-2018. The data, comprising of patient, procedure and provider factors that could influence postoperative pain and opioid requirements, was randomly split into training (80%) and validation (20%) datasets. Machine learning models of different classes were developed to predict categorized levels of postoperative opioid requirements using the training dataset and then evaluated on the validation dataset. Prediction accuracy was used to differentiate model performances. The five types of models that were developed returned the following accuracies at two different stages of surgery: 1) Prior to surgery-Multinomial Logistic Regression: 71%, Naïve Bayes: 67%, Neural Network: 30%, Random Forest: 72%, Extreme Gradient Boost: 71% and 2) End of surgery-Multinomial Logistic Regression: 71%, Naïve Bayes: 63%, Neural Network: 32%, Random Forest: 72%, Extreme Gradient Boost: 70%. Analyzing the sensitivities of the best performing Random Forest model showed that the lower opioid requirements are predicted with better accuracy (89%) as compared with higher opioid requirements (43%). Feature importance (% relative importance) of model predictions showed that the type of procedure (15.4%), medical history (12.9%) and procedure duration (12.0%) were the top three features contributing to model predictions. Overall, the contribution of patient and procedure features towards model predictions were 65% and 35% respectively. Machine learning models could be used to predict postoperative opioid requirements in ambulatory surgery patients and could potentially assist in better management of their postoperative acute pain.
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