Postoperative Serum Cortisol Levels Research Articles

A Comparative Study between the Efficacy of Ultrasound Guided Erector Spinae versus Quadratus Lumborum Plane Blocks in Laparoscopic Appendectomy

Abstract Background Laparoscopic appendectomy is more superior to open appendectomy in terms of wound site infections and pain intensity. Although the laparoscopic technique is minimally invasive, postoperative pain is inevitable, and it may affect the patients’ mobility and cause them to stay in the hospital for a more extended period. Aim of the Work to compare the effectiveness of erector spinae plane block and quadratus lumborum plane block as part of multimodal analgesia for reducing postoperative pain in patients undergoing laparoscopic appendectomy. Patients and Methods This prospective randomized controlled clinical trial was conducted at operative theatres, Anesthesiology, Intensive Care and Pain Management Department, Faculty of Medicine, Ain Shams University Hospitals from April until September 2023. Results During this study, 54 patients undergoing laparoscopic appendectomy were enrolled and divided into two equal groups; group A subjected to erector spinae block and group B subjected to quadratus lumborum block. Intraoperative, Post Anaesthesia Care Unit and postoperative haemodynamic, postoperative NRS score, first time of postoperative analgesic request, total amount of postoperative analgesia and serum cortisol levels were measured. In this study there was a significant difference between the two groups regarding NRS scores and total amount of analgesia needed post operatively. In this study, no statistically significant difference was observed between the two groups in terms of serum cortisol levels. In this study, no significant difference was found between the two groups regarding heart rate and mean arterial pressure. Conclusion Both QLB and ESPB are effective as post-operative analgesia techniques for laparoscopic appendectomy. However, our study showed that US-guided ESPB may provide better pain control than QLB. These results allows healthcare providers and patients to choose the most suitable technique based on individual preferences and clinical considerations. However, further research with larger sample sizes and multicentric studies would be valuable to confirm these findings and explore potential variations in different patient populations or surgical settings.

A randomised comparative study of erector spinae plane block versus low-dose ketamine-dexmedetomidine intravenous infusion as intraoperative opioid-free analgesia for modified radical mastectomy.

Opioid-sparing analgesia for acute postoperative pain after breast cancer surgery is crucial due to opioid-related side effects. The utilisation of erector spinae plane block and low-dose intravenous ketamine-dexmedetomidine are widely recognised as non-opioid analgesic methodologies. The objective of this study was to conduct a randomised trial to examine the analgesic efficacy of both approaches while minimising the use of opioids. Seventy-two female patients scheduled for unilateral modified radical mastectomy were recruited. They were allocated randomly to Group ESPB, which received ipsilateral ultrasound-guided erector spinae plane block by 20 mL bupivacaine 0.5% at the level of T5 after induction of general anaesthesia, and Group Ket-Dex, which received intravenous (IV) bolus 0.25 mg/kg of ketamine and 0.5 µg/kg of dexmedetomidine, followed by an IV infusion of 0.25 mg/kg of ketamine and 0.3 µg/kg of dexmedetomidine per hour. Total postoperative morphine consumption (24 h) was the primary outcome. The secondary outcomes were pain scores over 24 hours during rest, duration of analgesia, isoflurane consumption, time to awakening, postoperative nausea and vomiting (PONV), and postoperative serum cortisol level. The postoperative morphine consumption over 24-hour in Group ESPB was 3.26 mg (0-6.74) versus 2.35 mg (2.08-4.88) in Group Ket-Dex (P = 0.046). Group Ket-Dex had lower pain scores at rest, longer analgesia duration, longer awakening time, and lower postoperative serum cortisol levels. Intravenous low-dose ketamine-dexmedetomidine infusion intraoperatively with inhalational-based general anaesthesia provides superior opioid-sparing analgesia to that of ESPB in patients undergoing unilateral non-reconstructive modified radical mastectomy, with less postoperative opioid consumption and stress response.

Comparative Study of Levobupivacaine Versus Levobupivacaine With Dexmedetomidine as an Adjuvant in Transversus Abdominis Block for Postoperative Pain Relief in Abdominal Hysterectomy Patients: A Randomized, Double-Blind Study.

Background Adjuvants have been discovered to prolong the analgesic impact of local anesthetics (LA), while the transversus abdominis plane (TAP) block offers sufficient postoperative pain relief after various abdominal procedures. Nevertheless, the impact of the given LA will determine the duration of the TAP block. Thus, in this investigation, we aimed to estimate the analgesic impact of combining dexmedetomidine (DEX) with levobupivacaine in the TAP block for patients having an infraumbilical incision for an abdominal hysterectomy while under spinal anesthetic. Aim This study aimed to determine the analgesic effect of DEX (0.5 mcg/kg) to 20 ml of 0.25% levobupivacaine on each side in the TAPblock in patients undergoing total abdominal hysterectomy (TAH). Materials and methods Two groups of 30 patients each, with ASA grades 1 and 2, were randomly selected from patients. Group N, comprising 30 patients, had a bilateral TAP block using 2 mL of normal saline and 20 mL of 0.25% levobupivacaine. Group D (n = 30 patients) was given DEX at a dose of 0.5 mcg/kg (2 mL) in addition to 20 mL of 0.25% levobupivacaine given bilaterally. The TAP block was administered just after skin closure. Time of the initial analgesic dose administration; total fentanyl doses utilized as rescue analgesia; pain scores (numerical rating scale (NRS)) at 2, 4, 6, 8, 12, and 24 hours; and pre- and postoperative cortisol levels were also noted. For each group, 1 gram IV paracetamol was administered every eight hours. Drugs used for rescue analgesia (RA) were diclofenac 75 mg IV stat and fentanyl 1 mcg/kg. Results and discussion In addition to Group N having lower NRS scores at rest, Group D had a considerably longer time for initial rescue analgesia than Group N. There was also a significant decrease in the total fentanyl consumption and postoperative serum cortisol levels in Group D in contrast to Group N. Conclusion Potential adjuvant DEX prolongs postoperative analgesia in patients experiencing abdominal hysterectomy when used alongside LA in TAP.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Retrospective matched cohort analysis. Academic medical center/pituitary center. Patients with CD with surgical remission and surgically treated NFPA. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). The small sample of patients with autoimmune disease limited identification of independent risk factors. Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Recordati Rare Diseases Inc.

Effects of Propofol versus Sevoflurane on Postoperative Pain and Neuroendocrine Stress Response in Oocyte Pickup Patients.

Background Pain aggravates the autonomic response to stress and raises neuroendocrine stress hormone levels. We compared the effects of propofol and sevoflurane on postoperative pain and neuroendocrine stress hormones. A prospective, randomized, and controlled trial was conducted with 60 patients. Methods We randomly allocated patients to groups P (remifentanil/propofol, n = 30) and S (remifentanil/sevoflurane, n = 30). Preoperative blood samples were taken to measure serum adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), glucagon, cortisol, aldosterone, and prostaglandin E2 (PGE2) levels. Intraoperatively and postoperatively, clinical parameters were monitored at different time points. The hormone levels were again measured in the follicular fluid and blood postoperatively. Result Demographic data were similar. The preoperative serum aldosterone levels were significantly higher in group P (p=0.001). Preoperative and postoperative serum ACTH, glucagon, cortisol, and PGE2 levels were significantly different in group P (p=0.009, p=0.004, p=0.029, and p=0.002); serum ACTH, glucagon, and PGE2 levels increased while serum cortisol levels decreased postoperatively. In group S, serum CRH and aldosterone levels, both increased in the postoperative period compared to the preoperative (p=0.001, p=0.006). Postoperatively, glucagon and PGE2 levels were both higher in group P than group S (p=0.019, p=0.015). In postoperative follicular fluid, glucagon and PGE2 levels were higher in group P, while cortisol levels were higher in group S (p=0.001, p=0.007, and p=0.001). Conclusion The effects of anesthetic agents were different. In group P, in the preoperative and postoperative evaluation, ACTH, glucagon, and PGE2 increased postoperatively, while cortisol decreased. In group S, aldosterone and CRH increased postoperatively. Glucagon and PG E2 were higher in group P than S, postoperatively.

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 Insufficiency After Unilateral Adrenalectomy in Primary Aldosteronism: Long-Term Outcome and Clinical Impact.

Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). To study the incidence and long-term outcome of postoperative AI after uADX for PA. Prospective registry study (August 2014 until the end of 2018). Tertiary referral center. One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. Postoperative ACTH stimulation testing to identify patients with AI. Incidence of patients with postoperative AI and definition of long-term outcome. Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.

Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing's disease: implications for immediate reoperation and remission.

OBJECTIVESuccessful transsphenoidal surgery for adrenocorticotropin hormone (ACTH)-producing pituitary tumors is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate reoperation. However, little is known about the detailed temporal course of changes in serum cortisol in the immediate postoperative period, and the relationship of postoperative cortisol dynamics to remission and late recurrence.METHODSA single-center retrospective cohort analysis was performed for all patients undergoing pituitary surgery from 2007 through 2015. Standardized diagnostic and treatment algorithms were applied to all patients with potential Cushing's disease (CD), including microsurgical transsphenoidal adenomectomy (TSA) by a single surgeon. All patients had serum cortisol levels drawn at 6-hour intervals for 72 hours after surgery, and were offered reoperation within 3 days for normal or supranormal postoperative cortisol levels. Primary outcomes were 6-month remission and late recurrence; secondary outcomes were persistent postoperative hypocortisolism and surgical morbidity. Discriminatory levels of postoperative serum cortisol for predicting remission were calculated at various intervals after surgery using receiver operating characteristic (ROC) curves.RESULTSAmong 89 patients diagnosed with CD, 81 underwent initial TSA for a potentially curable lesion; 23 patients (25.8%) underwent an immediate second TSA. For the entire cohort, 6-month remission was achieved in 77.8% and late recurrences occurred in 9.5%, at a mean of 43.5 months. Compared with patients with a single surgery, those with an immediate second TSA had similar rates of remission (78.3% vs 77.6%) and late recurrence (5.6% vs 11.1%). The rate of hypocortisolism for patients with 2 surgeries (12/23, 52.2%) was significantly greater than that for patients with single surgeries (13/58, 22.4%; p < 0.001). There was no difference in the incidence of CSF leaks between the first and second operations. Remission was achieved in 58 (92.1%) of 64 patients who completed the 2-surgery protocol. The temporal course of postoperative serum cortisol levels among patients varied considerably, with subnormal nadir levels < 2 μg/dl occurring between 12 hours and 66 hours. Patients achieving remission had significantly lower mean serum cortisol levels at every time point after surgery (p < 0.01). By ROC curve analysis, nadir cortisol levels < 2.1 μg/dl were predictive of 6-month remission for the entire cohort over 3 days (positive predictive value [PPV] = 94%); discriminating cortisol levels for predicting remission on postoperative day (POD) 2 were < 5.4 μg/dl (PPV = 97%), although patients with remission after postoperative cortisol levels of 2-5 μg/dl had a significantly higher rate of late recurrence.CONCLUSIONSThere is substantial variation in the temporal course of serum cortisol levels over the first 72 hours after TSA for CD, with nadir levels predictive for remission occurring as late as POD 3. Although a cortisol level of 2.1 μg/dl at any point was an accurate predictor of 6-month remission, levels less than 5.4 μg/dl on POD 2 were reasonably accurate. These data may enable decisions regarding the efficacy of an immediate second surgical procedure performed during the same hospitalization; immediate reoperation is associated with excellent remission rates and low recurrence rates in patients otherwise unlikely to achieve remission, but carries a higher risk of permanent hypocortisolism.

The Use of Three-dimensional Printers for Partial Adrenalectomy: Estimating the Resection Limits

To avoid hormonal replacement after partial adrenalectomy (PA), establishing the precise limit of an adrenal gland resection is essential. Herein, we evaluated the use of three-dimensional (3D) adrenal gland printing and volumetry measurement before PA to improve the determination of the remnant gland volume. Concomitant total adrenalectomy and a contralateral PA were performed in a patient with primary macronodular adrenal hyperplasia that exhibited mild hypercortisolism, arterial hypertension, and diabetes. Before surgery, a 3D replica of the adrenal gland to be partially resected was printed and given to the surgeon. The volumetry of the gland was measured by computed tomography 3D image reconstruction. No postoperative complications were noted. Immediately after the surgery, the patient initiated corticosteroid replacement, which was interrupted 52 days later. At the 6-month follow-up, the patient stopped using medications for diabetes and reduced the number of antihypertensive medications from 5 to 1. The pre- and postoperative serum cortisol levels were, respectively, 28 and 8.7 mcg/dl (n 5-25 mcg/dl). The pre- and postoperative adrenocorticotropic hormone levels were, respectively, <5 and 88 pg/ml (n 7.2-63 pg/ml). The postoperative adrenal volume was 12% of the total preoperative adrenal volume. The use of 3D printing associated with adrenal volumetry might be a useful tool for the surgeon when performing PA, enabling an estimation of the remnant gland volume.

Efficacy of two doses of tramadol versus bupivacaine in perioperative caudal analgesia in adult hemorrhoidectomy.

Background:The study was conducted to evaluate the perioperative analgesic efficacy of the two doses of caudally administered tramadol versus bupivacaine in adult hemorrhoidectomy.Patients and Methods:A total of 90 patients, aged 20-50 years, undergoing hemorrhoidectomy were randomly scheduled to receive bupivacaine 0.25% in 20 ml (Group B; n = 30), tramadol 1 mg/kg in 20 ml (Group T1; n = 30), tramadol 2 mg/kg in 20 ml (Group T2; n = 30) through caudal route after induction of general anesthesia. Postoperative pain was assessed every hour until the visual analog scale was 6, which is 1st time for rescue analgesia. Postoperative sedation, hemodynamic changes, serum cortisol, and epinephrine levels and incidence of side effects were also evaluated.Results:Duration of analgesia was longer in Group T2 (20 [1.14] h] compared with the Group B (7 [1.2] h) or Group T1 (12 [0.75] h); all P < 0.001. There were no significant hemodynamic changes. There were not incidences of side effects.Conclusion:Caudal tramadol 2 mg/kg provided a longer duration of postoperative analgesia with rapid onset and no incidence of complications or adverse effects in adult hemorrhoidectomy.

Post-operative serum cortisol levels as predictors of recurrence in Cushing's disease

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

Is peri-operative steroid replacement therapy necessary for the pituitary adenomas treated with surgery? A systematic review and meta analysis.

BackgroundPatients with pituitary adenomas usually receive “stress dose” steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.MethodsWe searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.FindingsThere are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60–270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.

Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing’s Disease

To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia. Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage. A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 μg/dL and plasma ACTH <20 pg/mL. Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.

Increased long‐term remission after adequate medical cortisol suppression therapy as presurgical treatment in Cushing's disease

In the last decade, pre-operative medical cortisol suppression therapy has frequently been used in Cushing's disease to normalize cortisol concentrations pre-operatively. Our aim was to assess the efficacy of presurgical medical cortisol suppression therapy in Cushing's disease. We retrospectively assessed the medical files of all patients with Cushing's disease that received presurgical cortisol suppression therapy with ketoconazole or metyrapone and underwent subsequent transsphenoidal surgery between 1990 and 2010 at our centre. We retrieved the pretreatment regimen, adequacy of pretreatment, early postoperative serum cortisol levels, adverse effects and long-term remission status. Nineteen of 33 patients (58%) obtained long-term remission after pituitary surgery without additional postoperative therapy. Thirteen of 16 patients with adequate presurgical cortisol suppression therapy had postoperative cortisol concentrations <50 nmol/l. The 16 patients with adequate presurgical cortisol suppression had a higher long-term remission rate after primary surgery compared with the 13 patients with borderline or inadequate pretreatment (81% vs 38%; P < 0·05). Adequate presurgical cortisol suppression treatment with ketoconazole or metyrapone in Cushing's disease seems to be associated with suppressed postoperative cortisol concentrations and an increased long-term remission rate.

Recurrences of ACTH-Secreting Adenomas After Pituitary Adenomectomy Can Be Accurately Predicted by Perioperative Measurements of Plasma ACTH Levels

Adenomectomy is the treatment of choice for ACTH-secreting adenomas. Although the development of ACTH deficiency immediately after adenomectomy suggests surgical success, disease recurrence was reported in patients who developed hypocortisolism postoperatively. In the current study, we examined the value of measuring perioperative plasma ACTH and cortisol levels in predicting disease recurrence of patients with ACTH-secreting adenomas. Consecutive patients (n = 55; 41 females, 14 males) with clinical, biochemical, and histological documentation of ACTH-secreting adenomas were investigated after pituitary adenomectomy. All patients were followed with clinical monitoring and frequent measurements of plasma ACTH and serum cortisol levels, and none received glucocorticoids unless or until they developed symptoms of adrenal insufficiency or when their serum cortisol levels were ≤3 μg/dL. Postoperative serum cortisol levels reached ≤3 μg/dL in 46 of 55 and were ≥4 μg/dL in the remaining 9. Simultaneously measured plasma ACTH levels in the latter 9 patients were >40 ng/L when the serum cortisol reached its nadir. In contrast, among the 46 patients who had serum cortisol levels of ≤3 μg/dL, plasma ACTH levels measured simultaneously were ≤20 ng/L in 38 of 46 and >20 ng/L in the remaining 8. During a mean follow-up period of nearly 7 years, patients who had a nadir plasma ACTH of >20 ng/L developed recurrences even though their postoperative serum cortisol levels were ≤3 μg/dL. Despite profound hypocortisolemia after adenomectomy, a simultaneously measured plasma ACTH level of >20 ng/L in the perioperative period is highly predictive of future recurrence of ACTH-secreting adenomas.

Use of the histological pseudocapsule in surgery for Cushing disease: rapid postoperative cortisol decline predicting complete tumor resection

Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18-36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated. Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0-2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy. The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033). Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10-36 hours after surgery despite prolonged and severe hypercortisolism.

Hemodynamic correlates of serum cortisol in neonates after cardiopulmonary bypass*

To document preoperative and early postoperative serum cortisol levels among a group of neonates with complex congenital heart disease undergoing cardiopulmonary bypass surgery and to describe the relationship between serum cortisol and hemodynamic variables in the early postoperative period. Prospective observational substudy conducted within a randomized controlled trial. Tertiary-care pediatric cardiac intensive care unit. : We consecutively enrolled neonates undergoing a modified Norwood procedure or repair of interrupted aortic arch with ventricular septal defect in a randomized, placebo-controlled trial of triiodothyronine replacement. Methylprednisolone (30 mg/kg intravenously) was administered at anesthetic induction. We measured serum cortisol preoperatively and at 24 and 48 hrs postoperatively. Atrial filling pressures were documented 24 and 48 hrs after surgery. Oxygen consumption was measured and cardiac index was calculated 48 hrs after surgery. Spearman's correlation and linear regression were used to examine the relationship between serum cortisol and postoperative variables. Thirty-eight patients met eligibility criteria. Median serum cortisol levels 24 and 48 hrs postoperatively were 5.0 μg/dL (range 0.4-74.0) and 4.0 μg/dL (range 0.3-17.0), respectively (p = not significant). Greater atrial filling pressures were correlated with higher serum cortisol levels 24 hrs (r = .42, p = .019) and 48 hrs (r = .46, p = .022) after surgery. A lower cardiac index was correlated with higher serum cortisol levels 48 hrs postoperatively (r = -.49, p = .039), and this relationship remained significant after controlling for inotrope score, treatment with triiodothyronine, and atrial filling pressure in bivariate models. Systolic and diastolic BP did not correlate with serum cortisol at 24 or 48 hrs. Serum cortisol levels were low in the majority of subjects, although a wide range was observed. Higher cortisol levels were associated with greater atrial filling pressures and a lower cardiac index. The relationship between serum cortisol and cardiovascular performance after cardiopulmonary bypass in infants warrants further evaluation.

Immediate postoperative cortisol levels accurately predict postoperative hypothalamic–pituitary–adrenal axis function after transsphenoidal surgery for pituitary tumors

Accurate assessment of the hypothalamic-pituitary-adrenal (HPA) axis is critical for the appropriate management of patients with pituitary adenoma after transsphenoidal surgery. We examine the role of immediate postoperative cortisol levels to assess hypothalamic-pituitary-adrenal axis (HPA) axis function post-operatively. We performed preoperative cortrosyn stimulation test (CST) and measured immediate postoperative serum cortisol levels in 100 patients undergoing 104 transsphenoidal surgeries. These results were compared to those of the CST at 4-6 weeks postoperatively, which served as a measure of HPA axis function. The ability of immediate postoperative, day of surgery (DOS) cortisol levels to predict normal HPA axis function was determined using standard predictive analytic methods and confusion matrix calculations. We found that postoperative, DOS cortisol level > or =15 microg/dL is a sensitive and accurate predictors of normal postoperative HPA axis function, with a sensitivity of 98%, an accuracy of 97%, and a positive predictive value of 99%. Our data suggest that an immediate, postoperative, DOS cortisol level > or =15 microg/dL predicts distant, normal, post-operative HPA axis function following transsphenoidal surgery.

Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome?

To assess the results of transsphenoidal pituitary surgery in patients with Cushing's disease over a period of 18 years, and to determine if there are factors which will predict the outcome. Sixty-nine sequential patients treated surgically by a single surgeon in Newcastle upon Tyne between 1980 and 1997 were identified and data from 61 of these have been analysed. Retrospective analysis of outcome measures. Patients were divided into three groups (remission, failure and relapse) depending on the late outcome of their treatment as determined at the time of analysis, i.e. 88 months (median) years after surgery. Remission is defined as biochemical reversal of hypercortisolism with re-emergence of diurnal circadian rhythm, resolution of clinical features and adequate suppression on low-dose dexamethasone testing. Failure is defined as the absence of any of these features. Relapse is defined as the re-emergence of Cushing's disease more than one year after operation. Clinical features such as weight, sex, hypertension, associated endocrine disorders and smoking, biochemical studies including preoperative and postoperative serum cortisol, urine free cortisol, serum ACTH, radiological, histological and surgical findings were assessed in relation to these three groups to determine whether any factors could reliably predict failure or relapse after treatment. Of the 61 patients included in this study, 48 (78.7%) achieved initial remission and 13 (21.3%) failed treatment. Seven patients suffered subsequent relapse (range 22-158 months) in their condition after apparent remission, leaving a final group of 41 patients (67.2%) in the remission group. Tumour was identified at surgery in 52 patients, of whom 38 achieved remission. In comparison, only 3 of 9 patients in whom no tumour was identified achieved remission. This difference was significant (P = 0.048). When both radiological and histological findings were positive, the likelihood of achieving remission was significantly higher than if both modalities were negative (P = 0.038). There were significant differences between remission and failure groups when 2- and 6-week postoperative serum cortisol levels (P = 0.002 and 0.001, respectively) and 6-week postoperative urine free cortisol levels (P = 0.026) were compared. This allowed identification of patients who failed surgical treatment in the early postoperative period. Complications of surgery included transitory DI in 13, transitory CSF leak in 8 and transitory nasal discharge and cacosmia in 3. Twelve of 41 patients required some form of hormonal replacement therapy despite achieving long-term remission. Thirteen patients underwent a second operation, of whom 5 achieved remission. Transsphenoidal pituitary surgery is a safe method of treatment in patients with Cushing's disease. Operative findings, radiological and histological findings, together with early postoperative serum cortisol and urine free cortisol estimates may identify failures in treatment. Alternative treatment might then be required for these patients. Because of the risk of late relapse, patients require life-long follow-up.

Adrenal function following coronary bypass surgery

Little is known about adrenocortical function after coronary bypass surgery in which moderate to deep hypothermia and cardiopulmonary bypass are used particularly with intraoperative steroid administration. Therefore, we performed a pilot study in which immediately preoperative and 18-hour postoperative serum cortisol levels were determined in eight patients who received 1.0 to 1.5 gm of methylprednisolone intravenously during surgery; postoperative serum cortisol (3 ± 1 μg%) levels were lower than preoperative levels (15 ± 3 μg%, p < 0.05). To determine the possible cause of these striking findings, the effects of moderate to profound hypothermia and cardiopulmonary bypass upon adrenocortical functioning were investigated without the influence of intraoperative steroid administration. Serum cortisol and aldosterone levels and their response to adrenocorticotropic hormone (ACTH) (Cortrosyn) were determined before coronary bypass surgery and at various postoperative intervals in seven patients. Postoperative cortisol and aldosterone levels increased markedly over their preoperative values, reaching a maximum at 6 to 12 hours (cortisol 16 ± 8 vs 63 ± 23 μg%, p < 0.05, aldosterone 15 ± 5 vs 51 ± 22 ng%, p < 0.05). Adrenal response to ACTH was normal preoperatively, during rewarming from hypothermia, and 18 hours, and 7 days postoperatively. In summary, (1) normal adrenal responsiveness occurs after coronary bypass surgery, in spite of hypothermic cardiopulmonary bypass and the effects of anesthesia, and (2) a single dose of methylprednisolone during surgery is associated with markedly lower serum cortisol levels and prevents the usual adrenal stress response to bypass surgery for at least 18 hours postoperatively.