Postoperative Cortisol Research Articles

Toward better prediction of recurrence for Cushing’s disease: a factorization-machine based neural approach

Cushing's disease (CD) is a rare disease that occurs in 1.2–1.4 persons per million population per year. Recurrence prediction after transsphenoidal surgery (TSS) is important for determining individual treatment and follow-up strategies. Between 2000 and 2017, 354 CD patients with initial postoperative remission and long-term follow-up data were enrolled from Peking union medical college hospital (PUMCH) to predict recurrence, and PUMCH is one of the largest CD treatment centers in the world. We first investigated the effect of a factorization machine (FM)-based neural network to predict recurrence after TSS for CD. This method could automatically reduce a portion of the cross-feature selection work with acceptable parameters. We conducted a performance comparison of various algorithms on the collected dataset. To address the lack of interpretability of neural network models, we also used the local interpretable model-agnostic explanations approach, which provides an explanation in the form of relevant features of the predicted results by approximating the model behavior of the variables in a local manner. Compared with existing methods, the DeepFM model obtained the highest AUC value (0.869) and the lowest log loss value (0.256). According to the importance of each feature, three top features for the DeepFM model were postoperative morning adrenocorticotropic hormone level, age, and postoperative morning serum cortisol nadir. In the post hoc explanation phase, the above-mentioned importance-leading features made a great contribution to the prediction probability. The results showed that deep learning-based models could better aid neurosurgeons in recurrence prediction after TTS for patients with CD, and could contribute to determining individual treatment strategies.

Markers of recurrence in cushing’s disease: The role of post-operative serum cortisol and desmopressin test

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Efficacy and Safety of Stereotactic Radiotherapy in Cushing's Disease: A Single Center Experience.

To determine the efficacy and safety of stereotactic radiotherapy (RT) in patients with Cushing's disease (CD). The study included 38 patients [31 patients who received gamma knife radiosurgery (GKS) and 7 patients who received cyberknife hypofractionated RT (HFRT)] with CD. Hormonal remission was considered if the patient had suppressed cortisol levels after low dose dexamethasone, normal 24-hour urinary free cortisol (UFC), and lack or regression of clinical features. Biochemical control after RT was observed in 52.6% of the patients with CD and median time to hormonal remission was 15 months. Tumor size control was obtained in all of the patients. There was no significant relationship between remission rate and laboratory, radiological and pathological variables except for preoperative UFC. Remission rate was higher in patients with lower preoperative UFC. Time to remission increased in parallel to postoperative cortisol and 1mg DST level. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to hormonal remission. In this current single center experience, postoperative cortisol and 1mg DST levels were found as the determinants of time to remission. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to biochemical control . This latter finding might suggest a radioprotective effect of cortisol lowering medication use on peri-RT period.

The rules for predicting remission in patients with Cushing disease after successful endoscopic transnasal adenomectomy

The recurrence rate after successful transnasal adenomectomy in Cushing’s disease (CD) can reach 47%. We have previously shown that patients with ACTH levels less than 7 pg/ml recurred over 3 years 4.5 times less often than patients with higher levels of ACTH, patients with cortisol levels below 123 nmol/l — in 3.4 times less than at higher values of this hormone, however, these indicators are dissociated in 41% of cases, so it is not possible use them for prediction separately. To develop a method for managing patients after successful transnasal adenomectomy depending on prognosis. A monocenter retrospective comparative study included 349 patients (52 men, 297 women) with a confirmed diagnosis of CD, who underwent effective endoscopic transsphenoidal adenomectomy in 2007−2014. Various combinations of postoperative morning levels of ACTH and cortisol were analyzed. Based on the developed forecasting methods and their best characteristics, the following rules were formulated. If postoperative morning ACTH is less than 7 pg/ml and/or postoperative morning cortisol is less than 123 nmol/l, then the patient will remain in remission for 1 year with probability of 99% (95% CI 97%–100%) and for 3 years with probability of 86% (95% CI 80%–91%). The rules for predicting remission for 1 and 3 years for patients after neurosurgical treatment for CD are proposed. These rules are based on combinations of ACTH and cortisol levels.

Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis.

Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6months were excluded. The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2μg/dL (< 55nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250nmol v 1726nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2μg/dL (< 55nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2μg/dL (< 55nmol/L).

Early assessment of postoperative adrenal function is necessary after adrenalectomy for mild autonomous cortisol secretion

BackgroundThe diagnostic threshold for mild autonomous cortisol secretion using low dose, overnight, dexamethasone suppression testing is recognized widely as a serum cortisol ≥1.8 mcg/dL. The degree to which these patients require postoperative glucocorticoid replacement is unknown. MethodsWe reviewed adult patients with corticotropin (ACTH)-independent hypercortisolism who underwent unilateral laparoscopic adrenalectomy for benign disease with a dexamethasone suppression testing ≥1.8 mcg/dL at our institution from 1996 to 2018. Patients with a dexamethasone suppression testing of 1.8 to 5 mcg/dL were compared with those with a dexamethasone suppression testing >5 mcg/dL. ResultsWe compared 68 patients with a preoperative dexamethasone suppression testing of 1.8 to 5 mcg/dL to 53 patients with a preoperative dexamethasone suppression testing >5 mcg/dL. Preoperative serum ACTH (mean 10.0 vs 9.2 pg/mL), adenoma size (mean 3.4 vs 3.5 cm), and side of adrenalectomy (37 and 47% right) were similar between groups (P > .05 each). Patients with a dexamethasone suppression testing 1.8 to 5 mcg/dL were older (mean values 58 ± 11 vs 52 ± 16 years ; P = .01), less likely to be female (63 vs 81%; P = .03), had greater body mass indexes (33.1 ± 8.4 vs 29.1 ± 5.6; P = .01), and had lesser 24 hour preoperative urine cortisol excretions (32.6 ± 26.7 vs 76.1 ± 129.4 mcg; P = .03). Postoperative serum cortisol levels were compared in 22 patients with a dexamethasone suppression testing of 1.8 to 5 mcg/dL to 14 patients with a dexamethasone suppression testing >5 mcg/dL. Those with dexamethasone suppression testing 1.8 to 5 mcg/dL had greater postoperative serum cortisol levels (8.0 ± 5.7 vs 5.0 ± 2.6 mcg/dL; P = .03), were less likely to be discharged on glucocorticoid replacement (59% vs 89%; P = .003), and had a decreased duration of treatment (4.4 ± 3.8 vs 10.7 ± 18.0 months; P = .04). ConclusionAssessment of early postoperative adrenal function with mild autonomous cortisol secretion is necessary to minimize unnecessary glucocorticoid replacement.

Adrenal Function and Vasoactive-Inotrope Score (VIS) in Children after Cardiac Surgery

Purpose: To determine if a difference exists in vasoactive-inotrope score (VIS) between children with adrenal insufficiency (AI) and those without AI undergoing cardiopulmonary bypass (CPB) at the Children’s Hospital of Georgia at Augusta University Health. Methods: This is a single center retrospective and prospective observational study of consecutive pediatric cardiothoracic surgery patients (January 2018 – September 2018). Children 18 years of age or younger undergoing cardiothoracic surgery and CPB with a random post-operative cortisol level were included in the study. Data collected included demographic data as well as pre-, intra-, …

Cushing's disease: the desmopressin test as a compelling predictive marker of long-term remission after transsphenoidal surgery.

Transsphenoidal surgery (TSS) is the treatment of choice in Cushing's disease. However, recurrence rates are substantial and currently there are no robust predictors of late prognosis. As accumulating evidence challenge the accuracy of the traditionally used early postoperative cortisol values, alternative tests are required. The study of Cambos et al., published in a recent issue of the European Journal of Endocrinology, adds to the existing data that support a role of the desmopressin test as an early and reliable predictive marker in successfully TSS-treated patients. However, despite these promising data, the use of this test is hampered by the fact that it can be applied only in patients with a documented preoperative positive test. Moreover, the lack of robust criteria to define positive postoperative responses represents another major limitation.

SAT-248 Cushing’s Disease with Two ACTH-Producing Pituitary Tumors

Objective: The objective of this case report is to discuss a case of Cushing’s disease with two ACTH-producing pituitary tumors and emphasize consideration of repeat surgery as a treatment modality for unsuccessful initial surgery. Methods: We present a case of a patient with Cushing’s disease with two ACTH-producing pituitary tumors and a literature review. Results: A 36 year-old female found to have left supraclavicular fossa swelling was screened for Cushing’s syndrome. Midnight salivary cortisol levels elevated at 0.636 ug/dL and 0.316 ug/dL (<0.010–0.090 ug/dL). 24-hour urine cortisol 162 ug/24 hr (0–50 ug/24 hr). 1-mg dexamethasone suppression test 14.0 ug/dL. Serum morning cortisol 26.4 ug/dL with corresponding ACTH 66.7 pg/mL (7.2–63.3 pg/mL). MRI brain with and without contrast showed a 7-mm relatively hypoenhancing lesion of the anterior pituitary gland. 8-mg dexamethasone suppression test 2.7 ug/dL. She underwent transsphenoidal surgery (TSS) and pathology was consistent with a pituitary adenoma staining positive for ACTH. No residual tumor was seen. Postoperative morning serum cortisol 17.0 ug/dL and ACTH 79 pg/mL (9–46 pg/mL). She had repeat TSS and the area of resection was clean with no residual tumor but a second adenoma was found that was not visualized on MRI and was distinct from the initial lesion. Postoperative morning cortisol 0.7 ug/dL and ACTH <9 pg/mL (9–46 pg/mL). Pathology was consistent with pituitary adenoma staining positive for ACTH. She is now on steroids for central adrenal insufficiency. Discussion: First-line treatment for Cushing’s disease is surgical resection of the primary lesion (Nieman LK, Biller BMK, et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(8):2807–2831). Remission rates are 73–76% for selectively resected microadenomas but 43% for macroadenomas (Nieman et al. 2015). For patients who undergo a noncurative surgery, second-line therapies include repeat TSS, radiotherapy, medical therapy, and bilateral adrenalectomy. Repeat TSS is recommended particularly in patients who had evidence of incomplete resection or a pituitary lesion on imaging although this was not the case with our patient. Repeat TSS is cited to be successful in about 50–60% of cases (Patil CG, Veeravagu A, et al. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery. 2008;63(2):266–270) but carries an increased risk of hypopituitarism and lower likelihood of remission compared to initial surgery. Remission can be achieved more rapidly compared to other second-line treatments. Conclusion: In Cushing’s Disease with unsuccessful initial surgery, consideration for repeat TSS may be considered when there is access to an expert pituitary surgeon.

MON-304 Prolactin as a Surrogate Marker to Predict Long Term Postoperative Hypopituitarism After Transsphenoidal Resection of Pituitary Adenomas

Transsphenoidal surgery (TSS) is the first line treatment for pituitary adenoma. A well-known complication of TSS is hypopituitarism with a reported risk of 5-25% after resection of pituitary adenomas. A decrease in postoperative prolactin concentration was shown to be associated with postoperative hypopituitarism in a previous report. We hypothesized that in addition to clinical factors (preoperative hypofunction and adenoma size), biochemical factors (change in prolactin concentration and immediate post-operative hypofunction) can aid in predicting long term hypopituitarism as defined as ≥1 biochemically confirmed hypofunctioning pituitary axes 3 years after resection. A retrospective analysis of all patients undergoing TSS for both functioning and non-functioning pituitary adenomas at a tertiary center from January 2013 through December 2015 was performed. Prolactinomas were excluded. Of the 75 patients included, 21.3% (n=16) had at least one pituitary axis requiring replacement at 3 years post operatively. Mean age at presentation was 55 ± 16 years, 55% were female and 81% were Caucasian. Mean adenoma size was no different between normal pituitary function and hypopituitary groups (24.0 ± 11.9 mm versus 25.3 ± 10, p=0.7). Factors associated with long term hypopituitarism were older age (mean age 64 ± 4 years versus 53 ± 2 years, p = 0.02), preoperative secondary adrenal insufficiency (AM cortisol 6.4 ± 3.7 vs 12.0 ± 6.5 µg/dL; p = 0.03), preoperative secondary hypothyroidism (0.8 ± 0.2 vs 12.0 ± 6.5 ng/dL; p < 0.01), low immediate postoperative cortisol (5.3±3.1 vs 26.1±18.3 µg/d; p<0.01), and persistence of adrenal insufficiency (10.7% vs 2.7%; p<0.01) and secondary hypothyroidism (13.3% vs 5.3%; p<0.01) at 3 months. Change in prolactin concentration from preoperative to postoperative day 1-7 was not significantly different between groups (p=0.09) due to the higher variability in the hypopituitary group (median 0.2 ng/mL, IQR -0.5 - 0.8 ng/mL) compared to the normal pituitary function group (median 0.7 ng/mL, IQR 0.5-0.8 ng/mL). Adenoma size, optic chiasm and cavernous sinus involvement were not associated with long term hypopituitarism. In patients who developed postoperative hypopituitarism, there was a higher frequency of adenoma persistence or recurrence (20% vs 47%). There was a high rate of patients lost to follow up (56%). Older age, the presence of preoperative secondary adrenal insufficiency and hypothyroidism, and low day 1-7 postoperative cortisol concentration are factors that can be used to deem a patient high risk for future hypopituitarism. These patients should have close follow up with continued screening postoperatively. Contrary to prior reports, adenoma size and parasellar involvement were not associated which may be suggestive of surgical expertise. Prolactin concentrations proved not to be a good surrogate marker to predict long term hypopituitarism.

OR23-03 Post-Operative Day One Morning Cortisol Value as a Biomarker to Predict the Recurrence of Cushing Disease

Tumor removal by transsphenoidal surgery (TSS) is the first line treatment for Cushing disease (CD). However, recurrence is relatively common. A one week post-operative (post-op) nadir cortisol has been used as a biomarker to predict recurrence1. We identified 299 CD patients from our longitudinal multidisciplinary clinic or our institutional RPDR search tool who met biochemical diagnostic criteria1 and had undergone TSS between May 2008 and May 2018, to evaluate post-op cortisol levels as biomarkers to predict long-term remission and to characterize clinical features of Cushing syndrome. Predictors of recurrence were identified with logistic regression, using recurrence as the dependent variable, and a Kaplan-Meier survival curve analysis was performed to compare long-term remission after TSS among the 202 patients who reached initial remission and had at least 1 year of follow-up. The post-op day 1 morning (AM) cortisol had significant association with CD recurrence (OR=1.025, 95%CI:1.002-1.048, p=0.032). The time to recurrence was significantly longer in patients with post-op day 1 AM cortisol <5 μg/dL. In contrast, one week post-op nadir cortisol (OR=1.081, 95%CI: 0.989-1.181, p=0.086), urinary free cortisol (OR=1.032,95%CI: 0.994-1.07, p=0.098), or late night salivary cortisol (OR=1.383, 95%CI:0.841-2.274, p=0.201) had no significant correlation with recurrence. There were no significant differences in time to recurrence for post-op day 2 AM cortisol <5 μg/dL. Among patients who developed post-op adrenal insufficiency, recurrence was significantly lower if glucocorticoid replacement continued for more than one year. In addition, tumor proliferative index (MIB-1) had a significant correlation with recurrence (OR=1.287, 95%CI:1.106-1.498, p=0.001). The most common symptoms and signs of initial presentation of CD were weight gain (91.6%), central obesity (79.6%), menstrual disorders (77.9%), round face (65.9%), hypertension (63.2%), mood disorders (60.2%), dorsocervical fat deposition (59.9%), supraclavicular fat deposition (59.9%), osteoporosis (58.9%), fatigue (58.2%), bruising (55.9%) and facial hirsutism (54.2%). Most of the best discriminating CD features did not have high sensitivity, such as purple striae (31.4%), facial plethora (33.4%) and proximal muscle weakness (30.8%). Our data show that post-op day one morning cortisol level above 5 μg/dL had significant association with recurrence. In contrast, the one week post-op nadir cortisol level had no significant value to predict recurrence. Our data also suggest that nonspecific symptoms and signs of CD are more common than stereotypical signs. Reference: Nieman LK, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:2807-2831

MON-LB035 Adrenal Venous Sampling in the Lateralization of Acth-Independent Cushing Syndrome With Bilateral Adrenal Masses: A Case With a 5-Year Follow-Up

Background Nearly 25% of adrenal Cushing syndrome (CS) patients with bilateral adrenal masses have unilateral hypercortisolism, making localization crucial for surgical planning. Since there is no standardized protocol for adrenal venous sampling (AVS) in lateralizing adrenal hypercortisolism, we share our experience with a case of CS with bilateral adrenal masses in which lateralization via AVS permitted unilateral adrenalectomy. Clinical Case A 59-year-old woman with hypertension, hyperlipidemia, and prediabetes was hospitalized for worsening back pain and hypertension. Her BMI was 26.5 kg/m2, BP 173/93 mmHg, HR 73/min, she was anxious, diaphoretic, and hirsute. Glucose was 118 mg/dL and HbA1c 6.6%. Abdominal computed tomography revealed a type B aortic dissection with both right (6.1 x 3.1cm and 3.6 x 2.4cm), and left (largest 1.7 cm) sided adrenal masses. Plasma and 24 hour-urine metanephrine, normetanephrine and catecholamines, as well as plasma renin and aldosterone levels, were normal. AM cortisol on three different occasions was 21.30, 20.70, and 21.30 mcg/dL. Midnight cortisol was 17.8 mcg/dL, and 24-hour urine free cortisol on two occasions was 163 mcg (urine volume 3.4L with creatinine 1.14) and 99.2 mcg (urine volume 1.15L). After 1mg dexamethasone her AM ACTH and cortisol were <5 and 18.70 mcg/dL, respectively. Preoperative AVS was performed and 8mg of dexamethasone was administered the night prior to ensure ACTH suppression during the procedure, and epinephrine was measured to ascertain adequate adrenal vein cannulation. Cortisol levels (in mcg/dL) from the common iliac, right and left adrenal veins were 14.7, 61.5, and 23.5 at 0 minute and 15.2, 61.0, and 22.7 at 2 minutes, respectively. Epinephrine levels (in pg/dL) from the common iliac, right and left adrenal veins were 42, 577, and 3225 at 0 minutes, and 46, 718, and 2989 at 2 minutes. Despite higher epinephrine levels from the left adrenal, the cortisol ratio of the right adrenal vein to peripheral vein was 4.18 with the right-to-left ratio of 2.59 and 2.68 at 0 and 2 minutes, suggesting hypersecretion of cortisol from the right adrenal gland. Unilateral right adrenalectomy revealed a 5.6 cm adrenal adenoma arising in a background of adrenal cortical hyperplasia. Morning postoperative cortisol was 2.2 mcg/dL. She was placed on hydrocortisone and tapered over a 10-month period with remission maintained for more than 3.5 years post-operatively. Conclusion This case demonstrates the safety, usefulness, and necessity, of AVS in localizing cortisol production when bilateral adrenal masses are present. In addition, this case suggests that the use of high dose dexamethasone and measurement of catecholamines may be helpful for more accurate interpretation. More data on AVS in CS patients with bilateral adrenal masses is needed so a well-validated and standardized CS-specific ACS protocol can be developed.

Designing meditation for doctor well-being: can 'Om' help obstetrics and gynaecology doctors?

The study aimed to measure the impact of meditation on participants' ability to regulate brain wave activity in high-stress situations, control physiological stress responses and improve subjective wellbeing. Twelve obstetrics and gynaecology (O&G) doctors meditated for 20 minutes daily for 21 days utilising a portable EEG (electroencephalogram) providing instantaneous audio feedback. Their brain activity levels and salivary cortisol were measured before and after performing three surgical procedures. Participants were interviewed about their experiences and completed self-ratings of distress (e.g. DASS-21, Depression, Anxiety and Depression Scale). Data were analysed statistically and thematically. (a) Measures of pre- and post-operative brain activity showed no significantly higher levels of alpha waves. (b) Pre- and post-operative salivary cortisol levels did not significantly decrease. (c) DASS-21 scores showed significant decreases in levels of anxiety and stress. Results suggest that, with biofeedback meditation, O&G doctors can learn to reduce situational stress and improve mood overall through a focussed intervention.

Flurbiprofen axetil for postoperative analgesia in upper abdominal surgery: a randomized, parallel controlled, double-blind, multicenter clinical study.

To investigate the efficacy and safety of flurbiprofen axetil in postoperative analgesia in upper abdominal surgery. This was a multicenter, randomized, positive drug parallel controlled double-blind clinical study. Patients undergoing upper abdominal surgery were randomly divided to receive flurbiprofen axetil or tramadol. The VAS pain scores at rest and on coughing (pulmonary function training) were assessed immediately before drug usage (T1) to evaluate the efficacy of postoperative analgesia. Repeat assessment of the VAS was performed after T1. The timing of the recovery of the gastrointestinal function and the preoperative and postoperative IL-6, cortisol, and blood glucose levels were recorded as secondary endpoints. Vital signs and the occurrence of adverse reactions were evaluated for the assessment of safety. A total of 240 patients were enrolled in the current study; 119 used flurbiprofen axetil for postoperative analgesia. The VAS scores at rest and on coughing did not differ between the two groups to a statistically significant extent (P > 0.05). However, the reduction of the VAS score at rest in the flurbiprofen axetil group was greater than that in the tramadol group at 4-24h after T1. The reduction of the VAS score on coughing at 8h after T1 was greater in the flurbiprofen axetil group. The incidence of adverse reactions was significantly lower in the flurbiprofen axetil group, with only one adverse reaction recorded. In contrast, 18 adverse reactions were reported in the tramadol group. Flurbiprofen axetil showed superior efficacy to tramadol in early postoperative analgesia after upper abdominal surgery. Flurbiprofen axetil was associated with a significantly lower incidence of adverse reactions in comparison to tramadol.

The Influence of Persistent Organic Pollutants on Thyroidal, Reproductive and Adrenal Hormones After Bariatric Surgery.

Persistent organic pollutants (POPs) including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkylated substances (PFASs) are suspected endocrine disruptors. To evaluate the associations between POPs and thyroidal, reproductive, and adrenal hormones in a study population treated with bariatric surgery. Blood samples from a cohort of 63 participants before and 1 year after bariatric surgery were analyzed for 16 lipophilic POPs, 17 PFASs, and thyroidal, reproductive, and adrenal hormones. Participants reporting relevant medical conditions or interfering medication were excluded, and plausible confounders were corrected for in multiple regression analyses. Free thyroxine (fT4) showed a significant decrease from preoperative to postoperative follow-up, and regression analyses demonstrated that p,p'-dichlorodiphenyldichloroethylene (p,p-DDE) was inversely associated with the ratio free triiodothyronine/free thyroxine (fT3/fT4). Testosterone concentrations in male participants increased significantly in the study period, and sex hormone-binding globulin (SHBG) increased in both gender. Regression analyses showed positive associations between increased levels of lipophilic POPs and the raised postoperative testosterone and SHBG concentrations in males. For females, an inverse association between the sum perfluoroalkyl carboxylic acids (ΣPFCA) and SHBG was seen. Regression analyses of postoperative serum cortisol concentrations on changes in hexachlorobenzene (HCB) showed a non-significant inverse association. The results suggest that POPs may have an influence on the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-gonadal (HPG) axes after bariatric surgery. Because of small sample sizes and discrepancy in the sampling time points pre- and postoperatively, the observed hormonal impacts of POPs must be interpreted as associative and not causative. Further studies are needed to confirm the findings.

SURG-22. CUSHING’S DISEASE: A DIFFICULT TO TREAT NEURO-ONCOLOGICAL CONDITION

Abstract BACKGROUND Cushing disease (CD) comprises a spectrum of clinical manifestations secondary to hypercortisolism due to ACTH-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. Because of the significant rate of recurrence or persistence of CD, it is of interest to determine factors that may correlate with long-term outcomes following surgical intervention. OBJECTIVE The objective of our study is to determine the remission rate after surgery with special emphasis on factors affecting remission. METHODS Data of all patients undergoing surgery for CD from 2009 to 2017 was analyzed retrospectively. Transphenoidal resection was the preferred treatment with a recent trend in favor of endonasal endoscopic skull base approach. Post-operative cortisol level of &lt; 2 μg/dL was taken as remission and value between 2 and 5 μg/dL as possible remission. RESULTS 104 patients operated primarily for CD were included for analysis. 47 patients underwent microscopic surgery, 55 endoscopic surgery and two were operated trans-cranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were (1) type of surgery (p=0.01); endoscopy (88.23% remission) better than microscopy (56.6% remission) (2) postoperative day-1 morning cortisol (p=0.004) and; (3) postoperative day-1 morning ACTH (p=0.015). In multivariate analysis, however only postoperative day-1 cortisol was found to be significant as predictor of remission (p=0.02). CONCLUSION Postoperative plasma cortisol level is a strong independent predictor of remission and value less than 10.7µgm/dl can be taken as cut off for predicting remission. Remission provided by endoscopy appears to be significantly better than microscopic approach.

Early postoperative HPA-axis testing after pituitary tumor surgery: reliability and safety of basal cortisol and CRH test

PurposeTo assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary surgery.MethodsRetrospective cohort study of all patients undergoing endoscopic transsphenoidal surgery from 2010 to 2017, in whom early postoperative basal cortisol and/or CRH-stimulated cortisol secretion were available, including confirmation of adrenal function during follow-up. Patients with Cushing’s disease were excluded. Optimal test performances were assessed using ROC analysis.ResultsA total of 156 patients were included. Sensitivity and specificity of the CRH test were 78% and 90%, respectively, and 86% and 92% for basal cortisol, respectively, using an optimal cutoff of 220 nmol/L. Eight patients had false-negative test results with the CRH test (normal test but adrenal insufficient at follow-up), and six patients with basal cortisol, the majority of which had multiple pituitary hormone deficiencies and fluid imbalances. No clinical adverse events occurred in patients with false-negative test results. The diagnostic performance of a single basal cortisol measurement was superior to the CRH test.ConclusionsThe early postoperative basal cortisol is a safe and simple measurement to guide (dis)continuation of hydrocortisone replacement. However, disturbing factors, e.g., sodium balance disorders, contraceptives, untreated hypopituitarism, and illness impact the interpretation and in those cases this measure is unreliable. We propose an algorithm in which hydrocortisone replacement at discharge is based on basal cortisol <220 nmol/L on postoperative day 2 or 3 in a stable condition.

Prediction of recurrence and remission within 3years in patients with Cushing disease after successful transnasal adenomectomy.

Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. Effective method for prediction of recurrence and long-term remission within 3years after successful endoscopic transsphenoidal adenomectomy is proposed.

The Associations Between Cognitive Dysfunction, Stress Biomarkers, and Administered Anesthesia Type in Total Knee Arthroplasties: Prospective, Randomized Trial

Background: Postoperative cognitive dysfunction (POCD) is a serious complication associated with total knee arthroplasty (TKA) and has been shown to increase the length of hospital stay, cause functional impairment, and morbidity. Objectives: We aimed to determine whether POCD is associated with the use of general or regional anesthesia in patients undergoing TKA. Our hypothesis was that POCD would be reduced in the group that received regional analgesia without any sedations. Our secondary hypothesis was POCD would be associated with biomarkers of surgical stress. Study Design: Randomized controlled study between general and spinal anesthesia. Setting: Single-centered, university hospital, from January to October 2017. Methods: A total of 112 patients were assessed for eligibility, and a total of 57 patients completed the study. We divided the patients into general and regional anesthesia groups. Blood samples were obtained preoperatively at the first intraoperative, the third and the 24th postoperative hour. C-reactive protein (CRP), cortisol, insulin, and blood glucose levels were tested. We used 4 neurocognitive tests that were administered 1 day before operation, 7 days and 30 days after operation. Main outcome measures were neurocognitive tests scores for regional anesthesia without sedation and general anesthesia groups. Cortisol, glucose, insulin, and CRP levels. Results: Patients who received regional anesthesia showed significantly higher Mini-Mental State Examination (MMSE) scored compared with the general anesthesia at the seventh day (P = 0.037). In the general anesthesia group, patients showed significantly higher variations for the Stroop number difference. There were negative correlations between MMSE scores measured at postoperative day 7 and the 1-hour intraoperative cortisol measurements (r = –0.302; P = 0.022) and 3-hour postoperative cortisol measurements (r = –0.295; P = 0.026). Limitations: A limitation was the small number of patients. Conclusions: We demonstrate that regional anesthesia results in better neurocognitive test scores than general anesthesia in patients undergoing TKA. Patients who received regional anesthesia showed lower cortisol, higher insulin, and lower glucose levels. We recommend that patients who undergo arthroplasty surgeries should receive regional anesthesia to avoid POCD at the early stages of the postoperative period. Key words: Cognitive dysfunction, stress biomarkers, acute pain, regional anesthesia, spinal anesthesia

Management of Cushing's Disease: Changing Trend from Microscopic to Endoscopic Surgery

Cushing's disease (CD) is a spectrum of clinical manifestations due to adrenocorticotropic hormone-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. There has been a paradigm shift from microscopic to endoscopic transsphenoidal surgery in recent years. However, the efficacy of endoscopic transsphenoidal surgery has not been established. Therefore, it is of interest to determine the superiority of endoscopic transsphenoidal surgery, if any, over microscopic surgery. To assess the efficacy of endoscopic endonasal transsphenoidal surgery for the treatment of CD and to determine the factors affecting remission. Patients undergoing surgery for CD from 2009 to 2017 were analyzed retrospectively. Transsphenoidal resection was the preferred treatment, with recent trends in favor of the endonasal endoscopic skull base approach. Postoperative cortisol level of <2 μg/dL was taken as remission and value between 2 and 5 μg/dL as possible remission. In total, 104 patients operated primarily for CD were included for analysis; 47 patients underwent microscopic surgery, 55 endoscopic surgery, and 2 were operated transcranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were 1) type of surgery (P= 0.01); remission in endoscopy surgery (88.23%) is better than microscopy (56.6%); 2) postoperative day 1 morning cortisol (P= 0.004); and 3) postoperative day 1 morning ACTH (P=0.015). In multivariate analysis, only postoperative day 1 cortisol was found to be significant predictor of remission (P= 0.02). Postoperative plasma cortisol level is a strong independent predictor of remission. Remission provided by endoscopy is significantly better than the microscopic approach.