Risk factors for postoperative fever after laparoscopic adrenalectomy focusing on hormones produced: a case control study.

BACKGROUND: Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. METHODS: We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. RESULTS: There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p < 0.01). In contrast, postoperative fever developed in 6 out of 75 cases of Cushing syndrome (8%), which was significantly lower than in cases of non-Cushing syndrome (118/331, 35.6%, p < 0.01). CONCLUSION: Since postoperative fever after laparoscopic adrenalectomy is markedly affected by the hormone produced by pheochromocytoma and Cushing syndrome, it is important to carefully consider the need for treatment.

Long-term outcome of retroperitoneoscopic partial versus total adrenalectomy in patients with Cushing's syndrome.

BACKGROUND: We analyze the long-term outcome of surgery for Cushing's syndrome (CS) and the influence of the extent of surgical resection on the duration of postoperative cortisone substitution. METHODS: One-hundred forty-one patients (129 female, 12 males; mean age: 45.7 ± 12.8 years) operated between January 2000 to June 2020 were included in the analysis. Patients suffered from manifest (124) or subclinical (17) CS due to benign unilateral adrenal neoplasia. All tumors were removed by the posterior retroperitoneoscopic approach. 105 patients had total (TA) and 36 partial (PA) adrenalectomies. All patients were discharged with ongoing corticosteroid supplementation therapy. RESULTS: Follow-up data could be obtained for 83 patients. Twenty-four (1 male, 23 females; mean age 42.3 years) underwent PA and 59 TA (6 males, 53 females; mean age 44.6 years). Mean follow-up time was 107 ± 68 months (range: 6-243 months). The median duration of postoperative corticosteroid therapy was 9.5 months after PA and 11 months after TA (p = 0.1). Significantly, more patients after total adrenalectomy required corticosteroid therapy for more than 24 months (25% vs. 4%; p = 0.03). Recurrent ipsilateral disease occurred in one case after partial adrenalectomy and was treated by completion adrenalectomy. A case of contralateral recurrence associated with subclinical Cushing's syndrome was observed after total adrenalectomy. CONCLUSIONS: The risk of local recurrence after partial adrenalectomy in CS is low. Cortical-sparing surgery may shorten corticosteroid supplementation therapy after surgery.

Emergence of De Novo Conditions Following Remission of Cushing Syndrome: A Case Report and Scoping Review.

OBJECTIVE: Onset and exacerbation of autoimmune, inflammatory or steroid-responsive conditions have been reported following the remission of Cushing syndrome, leading to challenges in distinguishing a new condition versus expected symptomatology following remission. We describe a case of a 42-year-old man presenting with new-onset sarcoidosis diagnosed 12 months following the surgical cure of Cushing syndrome and synthesise existing literature reporting on de novo conditions presenting after Cushing syndrome remission. METHODS: A scoping review was conducted in Medline, Epub, Ovid and PubMed. Case reports and case series detailing adult patients presenting with new-onset conditions following Cushing syndrome remission were included. RESULTS: In total, 1641 articles were screened, 138 full-text studies were assessed for eligibility, and 43 studies were included, of which 84 cases (including our case) were identified. Most patients were female (85.7%), and the median reported age was 39.5 years old (IQR = 13). Thyroid diseases were the most commonly reported conditions (48.8%), followed by sarcoidosis (15.5%). Psoriasis, lymphocytic hypophysitis, idiopathic intracranial hypertension, multiple sclerosis, rheumatoid arthritis, lupus and seronegative arthritis were reported in more than one case. The median duration between Cushing remission and de novo condition diagnosis was 4.1 months (IQR = 3.75). Of those patients, 59.5% were receiving corticosteroid therapy at the time of onset. CONCLUSION: Our scoping review identified several cases of de novo conditions emerging following the remission of Cushing syndrome. They occurred mostly in women and within the year following remission. Clinicians should remain aware that new symptoms, particularly in the first year following the treatment of Cushing syndrome, may be manifestations of a wide range of conditions aside from adrenal insufficiency or glucocorticoid withdrawal syndrome.

Challenges in the postsurgical recovery of cushing syndrome: glucocorticoid withdrawal syndrome.

Glucocorticoid withdrawal syndrome is a challenging clinical phenomenon that can complicate the postsurgical recovery of Cushing syndrome. It is characterized by physical tolerance and dependence to supraphysiologic glucocorticoid exposure during active Cushing syndrome followed by the abrupt decline in cortisol levels after surgical treatment. The symptoms of glucocorticoid withdrawal often overlap with those of postoperative adrenal insufficiency and can be difficult for patients to cope with and for clinicians to treat. This mini review will discuss the clinical characteristics, pathophysiology, and management of glucocorticoid withdrawal syndrome while highlighting recent data in the field.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies.

The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

PURPOSE: Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. METHODS: Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. RESULTS: Twenty-five patients, mean age 40.60 ± 14.04 years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1ß were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1ß, and TNF-α levels, but ET-1 increased (p = 0.011). CONCLUSIONS: Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1ß following remission of CS.

Corticotropin-releasing hormone test predicts the outcome of unilateral adrenalectomy in primary bilateral macronodular adrenal hyperplasia.

PURPOSE: Primary bilateral adrenal hyperplasia (PBMAH) is associated with hypercortisolism and a heterogeneous clinical expression in terms of cortisol secretion and related comorbidities. Historically, treatment of choice was bilateral adrenalectomy (B-Adx); however, recent data suggest that unilateral adrenalectomy (U-Adx) may be an effective alternative. For the latter, factors predicting the postsurgical outcome (e.g., biochemical control) have not been identified yet. METHODS: PBMAH patients undergoing U-Adx for overt Cushing's syndrome (CS) in two tertiary care centers were retrospectively analysed. Remission was defined as a normalization of urinary free cortisol (UFC) without the need for medical treatment. The potential of hCRH test as a predictor of U-Adx outcome was evaluated in a subgroup. RESULTS: 23 patients were evaluated (69% females, mean age 55 years). Remission rate after U-Adx was 74% at last follow up (median 115 months from UAdx). Before U-Adx, a positive ACTH response to hCRH (Δ%ACTH increase > 50% from baseline) was associated with higher remission rates. CONCLUSIONS: Three of four patients with PBMAH are surgically cured with U-Adx. Pre-operative hCRH testing can be useful to predict long-term remission rates.

High prevalence of venous thrombotic events in Cushing's syndrome: data from ERCUSYN and details in relation to surgery.

OBJECTIVE: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. DESIGN: A retrospective observational cohort study. METHODS: Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. RESULTS: Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. CONCLUSION: Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.

PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome.

Background: We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets. Methodology: Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1). Results: Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes - FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) - were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively. Outcome: This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism.

[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

Laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA): an alternative approach for severe Cushing's syndrome.

Severe uncontrolled Cushing's syndrome (CS) is an acute life-threatening condition. As it is often not responsive to medical therapy, emergency bilateral adrenalectomy (BA) may present the only therapeutic option. Moreover, multiple bone fractures, representing one of the clinical consequences of hypercortisolism, may not permit both prone and lateral patient's positioning during surgery, thus making minimally invasive approaches nonfeasible. We report our preliminary experience with an alternative approach in this selected patients' category. Among 613 patients who underwent endoscopic adrenalectomy at our centre (34-5.6% BA) between January 1997 and October 2021, 3 patients were scheduled for laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA). Surgery was performed with patient in supine position, with fastened arms and legs to allow Trendelenburg and anti-Trendelenburg movements and lateral rotations. The procedure consisted in a synchronous bilateral adrenalectomy. A modern multi-articulated operative table provided rotations on the right and left side to perform left and right adrenalectomy, respectively. One male and two female patients with a mean age of 34 ± 3.1 years underwent La-TABA. Mean operative time was 200 ± 138.3 min. No perioperative complications were registered. Mean postoperative hospital stay was 8 ± 4.4 days. In very severe ACTH-dependent CS, BA should be performed as soon as possible. La-TABA may represent the most appropriate therapeutic option, as this patients' category is not able to tolerate prone and lateral positioning required during the conventional surgery. Despite the higher technical complexity of the procedure compared with the other endoscopic approaches to adrenalectomy, it retains the benefits of minimally invasive surgery in terms of postoperative complications and recovery.

Unexpected exacerbation of cryptococcal meningitis after unilateral adrenalectomy in a PMAH patient: a case report and literature review.

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient. CASE PRESENTATION: A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died. CONCLUSION: Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice.

Recent Updates on the Management of Adrenal Incidentalomas.

Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing's syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 µg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.

Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study.

OBJECTIVE: Glucocorticoid withdrawal syndrome (GWS) is a scarcely studied phenomenon that complicates the recovery following surgical remission of hypercortisolism. We aimed to characterize the presence and trajectory of glucocorticoid withdrawal symptoms in the postoperative period and to determine presurgical predictors of GWS severity. DESIGN: Longitudinal observational study. METHODS: Glucocorticoid withdrawal symptoms were prospectively evaluated weekly for the first 12 weeks following surgical remission of hypercortisolism. Quality of life (CushingQoL and Short-Form-36) and muscle function (hand grip strength and sit-to-stand test) were assessed at the baseline and at 12 weeks after surgery. RESULTS: Prevalent symptoms were myalgias and arthralgias (50%), fatigue (45%), weakness (34%), sleep disturbance (29%), and mood changes (19%). Most symptoms persisted, while myalgias, arthralgias, and weakness worsened during weeks 5-12 postoperatively. At 12 weeks after surgery, normative hand grip strength was weaker than at baseline (mean Z-score delta -0.37, P = .009), while normative sit-to-stand test performance improved (mean Z-score delta 0.50, P = .013). Short-Form-36 Physical Component Summary score worsened (mean delta -2.6, P = .015), but CushingQoL score improved (mean delta 7.8, P < .001) at 12 weeks compared to baseline. Cushing syndrome (CS) clinical severity was predictive of postoperative GWS symptomology. CONCLUSION: Glucocorticoid withdrawal symptoms are prevalent and persistent following surgical remission of hypercortisolism with baseline CS clinical severity predictive of postoperative GWS symptom burden. Differential changes observed in muscle function and quality of life in the early postoperative period may reflect the competing influences of GWS and recovery from hypercortisolism.

Thirty day postoperative outcomes following laparoscopic adrenalectomy for functional adrenal tumors.

BACKGROUND: Functional adrenal tumors (FATs) are rare and if left untreated, there is a substantial risk of morbidity and mortality due to uncontrolled excess hormone secretion. The three most common FATs are cortisone-producing tumors (hypercortisolism), aldosterone-producing tumors (hyperaldosteronism), and catecholamines-producing tumors (pheochromocytomas). The study aims to evaluate demographic characteristics and 30-day outcomes after laparoscopic adrenalectomy of FATs. METHODS: Patients who underwent laparoscopic adrenalectomy for FATs were selected from the ACS-NSQIP database (2015-2017), and divided into three groups (hyperaldosteronism, hypercortisolism, and pheochromocytoma). Preoperative demographics, medical comorbidities, and 30-day postoperative outcomes among the three groups were analyzed using the chi-squared test, analysis of variance (ANOVA) and Kruskal-Wallis one-way analysis of variance. Multivariable logistic regression was performed to assess the effects independent variables on the likelihood of increased overall morbidity. RESULTS: Of a total of 2410 patients who underwent laparoscopic adrenalectomy, 345 (14.3%) patients with FATs were included. Patients in the hypercortisolism group were younger, had higher proportion of females, had higher BMI, had a higher proportion of White ethnicity and had a higher proportion of diabetes. The hyperaldosteronism group had a higher proportion of Black ethnicity and a higher proportion of hypertension (HTN) requiring medication. Thirty day postoperative outcomes showed that the pheochromocytoma group had a higher rate of serious morbidity, overall morbidity, and highest readmission rates. There were three deaths, 1 in the pheochromocytoma and 2 in the hypercortisolism groups. Operative time (in minutes) was longer in the hypercortisolism group. Median length of stay was higher in hypercortisolism (2 days) and pheochromocytoma (1.5 day) groups. CONCLUSION: Functional adrenal tumors show distinct variations in patient demographics and postoperative outcomes. It is essential to use this information during the preoperative period to optimize patients prior to intervention and counsel patients about potential postoperative outcomes.

Substantial changes in inflammatory and cardiovascular biomarkers in patients with autonomous cortisol secretion.

OBJECTIVE: To map inflammatory biomarkers in patients with autonomous cortisol secretion (ACS) and overt Cushing syndrome (CS). METHOD: Observational study including serum from prospectively included patients with ACS (n = 63), adrenal CS (n = 2), pituitary CS (n = 8), and healthy subjects (n = 120). Serum samples were analysed for 92 inflammatory biomarkers using proximity extension assay (OLINK). RESULTS: Combined, the ACS and CS patients displayed significant differences in levels of 49/92 inflammatory biomarkers (46 increased/3 decreased) compared with healthy controls. No differences in biomarker levels were found between ACS and overt CS, and none of the biomarkers correlated with the degree of hypercortisolism. Postoperative samples were available for 17 patients, median 24 months (range 6-40) after surgery and biochemical curation. There was no significant normalization of the biomarkers postoperatively. CONCLUSION: There was a systemic rise in inflammatory biomarkers in patients with ACS and CS, not correlated to the degree of hypercortisolism. These biomarkers were not normalized following biochemical cure.

Cushing's Syndrome Is Associated With Early Medical- and Surgical-Related Complications Following Total Joint Arthroplasty: A National Database Study.

BACKGROUND: Cushing's syndrome (CS) is a disorder characterized by exposure to supraphysiologic levels of glucocorticoids. The purpose of this study was to evaluate the association between CS and postoperative complication rates following total joint arthroplasty (TJA). METHODS: Patients diagnosed with CS undergoing TJA for degenerative etiologies were identified from a large national database and matched 1:5 to a control cohort using propensity scoring. Propensity score matching resulted in 1,059 total hip arthroplasty (THA) patients with CS matched to 5,295 control THA patients and 1,561 total knee arthroplasty (TKA) patients with CS matched to 7,805 control TKA patients. Rates of medical complications occurring within 90 days of TJA and surgical-related complications occurring within 1 year of TJA were compared using odds ratios (ORs). RESULTS: The THA patients with CS had higher incidences of pulmonary embolism (OR 2.21, P = .0026), urinary tract infection (UTI) (OR 1.29, P = .0417), pneumonia (OR 1.58, P = .0071), sepsis (OR 1.89, P = .0134), periprosthetic joint infection (OR 1.45, P = .0109), and all-cause revision surgery (OR 1.54, P = .0036). The TKA patients with CS had significantly higher incidences of UTI (OR 1.34, P = .0044), pneumonia (OR 1.62, P = .0042), and dislocation (OR 2.43, P = .0049) and a lower incidence of manipulation under anesthesia (MUA) (OR 0.63, P = .0027). CONCLUSION: CS is associated with early medical- and surgical-related complications following TJA and a reduced incidence of MUA following TKA.

Laparoscopic adrenalectomy for adrenal tumors with endocrine activity: Perioperative management pathways for reduced complications and improved outcomes.

The major adrenal tumors with endocrine activity are primary aldosteronism, Cushing's syndrome/mild autonomous cortisol secretion, and pheochromocytoma/paraganglioma. Excessive aldosterone secretion in primary aldosteronism causes cardiovascular, renal, and other organ damage in addition to hypertension and hypokalemia. Cortisol hypersecretion in Cushing's syndrome/mild autonomous cortisol secretion causes obesity, hypertension, impaired glucose tolerance, and cardiometabolic syndrome. Massive secretion of catecholamines in pheochromocytoma/paraganglioma causes hypertension and cerebrocardiovascular disease due to rapid blood pressure fluctuation. Moreover, pheochromocytoma multi-system crisis is a feared and possibly fatal presentation of pheochromocytoma/paraganglioma. Thus, adrenal tumors with endocrine activity are considered an indication for adrenalectomy, and perioperative management is very important. They have a risk of perioperative complications, either due to direct hemodynamic effects of the hormone hypersecretion or due to hormone-related comorbidities. In the last decades, deliberate preoperative evaluation and advanced perioperative management have significantly reduced complications and improved outcomes. Furthermore, improvements in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduced morbidity and mortality. However, there are still several challenges to be considered in the perioperative care of these patients. There are very few data available prospectively to guide clinical management, due to the rarity of adrenal tumors with endocrine activity. Therefore, most guidelines are based on retrospective data analyses or small case series. In this review, the latest knowledge is summarized, and practical pathways to reduce perioperative complications and improve outcomes in adrenal tumors with endocrine activity are presented.

Cushing syndrome caused by an ectopic ACTH-producing pituitary adenoma of the clivus region: A rare case report and literature review.

RATIONALE: Ectopic ACTH-producing pituitary adenoma (EAPA) of the clivus region is extraordinarily infrequent condition and merely a few reports have been reported to date. PATIENT CONCERNS: The patient was a 53-year-old woman who presented with Cushing-like appearances and a soft tissue mass in the clivus region. DIAGNOSES: The final diagnosis of clivus region EAPA was established by clinical, radiological and histopathological findings. INTERVENTIONS: The patient underwent gross total clivus tumor resection via transsphenoidal endoscopy. OUTCOMES: Half a year after surgery, the patient Cushing-like clinical manifestations improved significantly, and urinary free cortisol and serum adrenocorticotropin (ACTH) returned to normal. LESSONS: Given the extreme scarcity of these tumors and their unique clinical presentations, it may be possible to misdiagnose and delayed treatment. Accordingly, it is especially crucial to summarize such lesions through our present case and review the literature for their precise diagnosis and the selection of optimal treatment strategies.

[Dynamics of NT-proBNP and ST2 levels as markers of heart failure in patients with endogenous Cushing syndrome (hypercortisolism)].

AIM: To evaluate frequency of heart failure syndrome in patients with endogenous hypercortisolism and to establish relationship between effective treatment for hypercortisolism and regression of heart failure with particular emphasis on the observation of NT-proBNP and ST2 levels. MATERIALS AND METHODS: 56 patients with endogenous hypercortisolism (45 female, mean age 47 years [36; 55] hospitalized with endogenous hypercortisolism to National Medical Research Center for Endocrinology were enrolled in the study. All patients underwent comprehensive clinical investigation including expert echocardiography with speckle tracking and evaluation of NT-proBNP and ST2 cardiac biomarkers at baseline and 6 months after surgical treatment. RESULTS: According to clinical data and elevated biomarkers of cardiac stress 28 out of 56 patients (50%) at baseline met the criteria for heart failure. 20 patients were included in the final analysis. Follow-up investigation with focus on changes in NT-proBNP and ST2 levels demonstrated that surgical correction of endogenous hypercortisolism resulted in resolution of heart failure syndrome in 11 patients (55%). CONCLUSION: These preliminary data suggest that signs and symptoms of heart failure are observed in patients with endogenous hypercortisolism in about half the cases. Surgical correction results in resolution of heart failure in approximately two thirds of the cases. Prospective evaluation NT-proBNP and ST2 levels may provide important diagnostic and prognostic information in patients with endogenous hypercortisolism.