The Impact of Obesity on the Resolution of Hypertension Following Adrenalectomy for Primary Hyperaldosteronism.

BACKGROUND: This study aims to determine the impact of patient obesity on the resolution of hypertension and pill burden post-adrenalectomy for PA. Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension that may be remedied with surgery (unilateral adrenalectomy). Obesity may independently cause hypertension through several mechanisms including activation of the renin-angiotensin-aldosterone pathway. The influence of obesity on the efficacy of adrenalectomy in PA has not been established. METHODS: This is a retrospective analysis of prospectively collected data on patients undergoing adrenalectomy for PA at a single, tertiary-care surgical centre from January 2015 to December 2020. Electronic health records of patients were screened to collect relevant data. The primary outcomes of the study include post-operative blood pressure, the reduction in the number of anti-hypertensive medications and potassium supplementation burden post-adrenalectomy. RESULTS: Fifty-three patients were included in the final analysis. There was a significant reduction in the blood pressure and the number of anti-hypertensive medications in all patients after adrenalectomy (p < 0.001). Of the 34 patients (64.2%) with pre-operative hypokalaemia, all became normokalaemic and were able to stop supplementation. However obese patients required more anti-hypertensive medications to achieve an acceptable blood pressure than overweight or normal BMI patients (p < 0.01). Multivariate logistic regression analysis showed that male gender and BMI were independent predictors of resolution of hypertension (p <0.01). CONCLUSION: Unilateral adrenalectomy improves the management of hypertension and hypokalaemia when present in patients with PA. However, obesity has an independent deleterious impact on improvement in blood pressure post-adrenalectomy for PA.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Posterior Retroperitoneoscopic Versus Laparoscopic Transperitoneal Adrenalectomy: A Systematic Review by an Updated Meta-Analysis.

BACKGROUND: Two main minimal access adrenalectomy techniques are available: laparoscopic transperitoneal (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA). This study aims to compare these approaches in an updated meta-analysis of randomised controlled (RCT) and non-randomised comparative (NRT) trials. METHODS: A systematic search of comparative LTA and PRA studies was performed. Standard demographic and surgical data were recorded. Outcome measures compared included: operative time, estimated blood loss (EBL), conversion to open, post-operative pain, time to oral intake and ambulation, early morbidity, hospital length of stay (HLOS) and mortality. Quality of RCTs and NRTs was assessed using Cochrane and ROBINS-I, respectively, and heterogeneity using the I2 test. Dichotomous and continuous variables were compared using odds ratios and mean/standard difference. Studies were then combined using the Mantel-Haenszel method. Meta-analysis was performed by fixed- and random-effect models. RESULTS: Following exclusions, 12 studies were included in the analysis: 3 RCTs and 9 NRTs. These reported a total of 775 patients: 341 (44%) PRA and 434 (56%) LTA. Demographics were similar except for tumour size which was smaller (by 0.78 cm) in PRA (p = 0.003). Significant differences in outcome were seen in EBL (18 mls less in PRA, p = 0.006), time to oral intake (3.4 h sooner in PRA p = 0.009) and HLOS (shorter in PRA by 0.84 day, p = 0.001). CONCLUSIONS: This analysis demonstrates that while PRA tends to be performed for smaller tumours it allows for less EBL, earlier post-operative oral intake and shorter hospital stays. In appropriately selected patients, it represents an invaluable tool in the endocrine surgeon's armamentarium.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Development of an ontology for laparoscopic transabdominal adrenalectomy via a comprehensive modified Delphi survey and its validation on a multicentric pilot data set for surgical training and future video analysis with machine learning algorithms.

Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts.

Redefining the stress cortisol response to surgery.

BACKGROUND: Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. METHODS: Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. RESULTS: Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. CONCLUSIONS: The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.

Adrenal surgery in England: better outcomes in high-volume practices.

AIMS AND BACKGROUND: Adrenal surgery is performed by a variety of surgical specialities in differing environments and volumes. International data suggest that there is a correlation between adrenal surgery volume and outcomes but there are no UK data to support this or UK surgical guidelines. A multidisciplinary team representing the stakeholders in adrenal disease is preparing a national guidance on adrenal surgery. A review of the outcomes for adrenal surgery in England was performed to correlate outcomes with the volume of surgeon practice. METHODS: Hospital Episode Statistics (HES) data for the National Health Service (NHS) in England in the tax year 2013-2014 were examined for adrenal surgery. Length of hospital stay and rate of postoperative readmission were assessed as surrogate quality markers and a comparison made between 'high-' and 'low-' volume surgeons. RESULTS: A total of 795 adult adrenalectomies were performed by 222 different surgeons with a range of between 1 and 34 adrenalectomies performed per surgeon. Only thirty-six (16%) adrenal surgeons performed 6 or more adrenalectomies. A total of 186 surgeons (84%) performed a median of one adrenalectomy a year. Length of stay and readmission rate within thirty days of operation was 60% longer and 47% higher, respectively, when performed by low-volume surgeons. CONCLUSION: The current provision of adrenal surgery in the UK is not in the best interests of patients and is not cost-effective for the NHS. Adrenal surgery is best performed by higher volume surgeons in centres with dedicated adrenal multidisciplinary teams expert in all aspects of care of the adrenal patient.

(18)F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma.

PURPOSE: To evaluate the performance of (18)F-L-dihydroxyphenylalanine ((18)F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. METHODS: We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone (18)F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. RESULTS: (18)F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of (18)F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. CONCLUSION: (18)F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by (18)F-DOPA PET/CT.

Learning curve of vessel cannulation in rats using cumulative sum analysis.

BACKGROUND: Intravascular access routes are widely used for administering agents or taking blood samples in rodents. Vessel cannulation in rats is a technically challenging procedure with a risk for significant complications. The use of cumulative sum (CUSUM) analysis allows continuous monitoring of the performer's outcomes to evaluate the learning curve for a particular procedure. The aim of the present study was to assess a researcher's learning curve in the cannulation of the jugular and femoral vein in rats using CUSUM analysis. MATERIALS AND METHODS: A single researcher performed two hundred microsurgical operations between September 2012 and September 2013. The animals (male Wistar rats) were anesthetized with isoflurane whereas the right jugular vein and the left femoral vein were catheterized. Prospective data were collected and analyzed using CUSUM analysis. For the purposes of the study, the rat population was divided in four groups based on the order of studies; group 1 represents the first 50 animals cannulated, group 2 the next batch of 50 animals, and so forth. RESULTS: The operating times required for cannulation of the jugular vein for groups 1, 2, 3, and 4 were 24.6 ± 4.8, 15.9 ± 2.5, 15.2 ± 3.2, and 15.7 ± 3.3 min, respectively. Group 1's operating time was significantly longer than all the other groups (P < 0.001 compared with all other groups). The operating times for groups 2, 3, and 4 did not differ significantly (P > 0.05). The cannulation of the femoral vein required a mean of 32 ± 5.3 min for group 1, 24.9 ± 5.7 min for group 2, 18.4 ± 4 min for group 3, and 17.2 ± 3.4 min for group 4. The operating time of group 1 was significantly longer when compared with all groups (P < 0.001 for all groups). Group 2 also had a longer operating time than groups 3 and 4 (P < 0.001 compared with both groups). Groups 3 and 4 did not show any statistical significant difference when their operating time was compared (P > 0.05). CUSUM analysis suggested that the number of cases required to achieve the required experience to most effectively cannulate the jugular and femoral vein is approximately 50 and 100 cases, respectively. The adverse effects of the procedure included two unexpected deaths, both of which occurred in group 1 (0.5% in total). CONCLUSIONS: The authors' experience regarding the learning curve of the cannulation of the femoral and jugular vein in rats from 200 animals operated over a period of 1 y for the evaluation of the pharmacokinetic properties of drug candidates suggests significant experience is required to optimize the operating time required for the procedure.

Gallium-68 Dotatate PET/CT is superior to other imaging modalities in the detection of medullary carcinoma of the thyroid in the presence of high serum calcitonin.

OBJECTIVE: Medullary carcinoma of the thyroid (MTC) is a rare neuroendocrine tumour (NET) that expresses somatostatin receptors on the cell membrane and secretes calcitonin. Surgery is the primary curative modality but is achieved only when the diagnosis is timely so there is a high rate of persistent and recurrent disease indicated by a rise in the serum calcitonin levels. Successful management of recurrent disease requires accurate localisation with cross sectional and functional imaging. The introduction of gallium-68-Dotatate ((68)Ga-Dotatate) peptides positron emission tomography/computerized tomography (PET/CT) has significantly improved the detection of NET and has been reported as a valuable adjunct in MTC localisation. We retrospectively reviewed our cases of MTC to correlate the detectability of (68)Ga-Dotatate in relation to calcitonin levels and assess suitability of inoperable patients for peptide receptor radionuclide therapy (PRRT). SUBJECTS AND METHODS: Seven patients (age range 31-66 years, M:F 3:4) with raised calcitonin (mean=7,143pg/mL) were referred for (68)Ga-Dotatate PET/CT scan for localisation of persisting recurrent MTC. Six patients were known to have MTC treated with thyroidectomy and one patient was presenting for the first time. All patients had multiple imaging including ultrasound (US), CT, magnetic resonance imaging (MRI), fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET/CT and iodine-123-metaiodobenzylguanidine ((123)I-MIBG). Positive findings were defined as areas of increased uptake other than the organs of normal distribution and were correlated with results of biopsies, other imaging, long term monitoring of calcitonin and clinical follow up. RESULTS: In 6/7 patients with very high serum calcitonin (range= 672-37,180, mean=8,320pg/mL) (68)Ga-Dotatate PET/CT confirmed the presence of active disease seen on other modalities or detected hitherto unsuspected lesions. In at least 3 cases, (68)Ga-Dotatate PET/CT showed many more lesions compared to other imaging combined. In 1/7 patient (68)Ga-Dotatate PET/CT was negative in line with a relatively low calcitonin level (80pg/mL) and negative disease on fine needle aspiration. CONCLUSION: (68)Ga-Dotatate PET/CT is an effective tool for localising metastatic spread of MTC. It appears to be most effective in the presence of higher levels of serum calcitonin, probably in excess of 500pg/mL. The results of our small cohort had an impact on staging and management with the introduction of peptide receptor radionuclide therapy for inoperable disease.

Associations of serum 25-hydroxyvitamin D with circulating PTH, phosphate and calcium in patients with primary hyperparathyroidism.

BACKGROUND: Despite NIH clinical recommendations, many clinicians are reluctant to replace vitamin D in patients with hypercalcaemia with primary hyperparathyroidism (PHP) due to concerns over aggravating hypercalcaemia. Furthermore, the optimum level of vitamin D replacement in PHP remains unclear. METHODS: We performed a large retrospective study to determine whether a relationship exists between serum 25-hydroxyvitamin D levels, calcium and other important biochemical markers in patients with PHP. Serum, plasma and urinary biochemical measurements were collected from 251 patients with hypercalcaemia diagnosed with PHP. RESULTS: When examining overall mean circulating levels during clinical follow-up, serum 25-hydroxyvitamin D correlated highly significantly with plasma parathyroid hormone (PTH) (r = -0.23, P = 0.0003) and serum phosphate (r = 0.16, P = 0.0119). No significant relationship was observed between serum calcium and 25-hydroxyvitamin D (r = 0.002, P = 0.98). Mean plasma PTH during clinical follow-up was 51% lower in patients with serum 25-hydroxyvitamin D > 60 nm when compared with patients who had 25-hydroxyvitamin D < 20 nm (P < 0.01). CONCLUSIONS: Patients with PHP who have 25-hydroxyvitamin D levels > 60 nm have significantly reduced PTH hypersecretion when compared with patients with deficient vitamin D levels, without exhibiting worse hypercalcaemia.

Retroperitoneoscopic or laparoscopic adrenalectomy? A single-centre UK experience.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the "gold standard" approach to benign adrenal tumours. Retroperitoneoscopic adrenalectomy (RA) is an increasingly popular alternative. The purpose of this study was to compare our preliminary experience with RA to the more established LA. METHODS: Data on patients undergoing adrenalectomy over a 2-year period from 2010 were reviewed. Patients undergoing open adrenalectomy, bilateral adrenal surgery, or paraganglioma resection were excluded. The LA and RA patients were compared according to their operative time, time to first oral intake, complications, analgesic requirements, and length of hospital stay. Further analysis was performed on patients matched for all patient and disease-related criteria. Statistical analysis was performed using the χ (2) test and the Mann-Whitney U test as appropriate. RESULTS: A total of 71 adrenalectomies that fit the inclusion criteria were performed during the period studied of which 36 patients underwent LA and 35 patients underwent RA. Mean tumour size differed between the two groups (2.83 cm in RA group vs. 4.1 cm in LA group; p = 0.033). Operative time, time to first oral intake, analgesic requirements, length of hospital stay, and postoperative complications were all significantly lower in the RA group. Analysis of matched patients showed a significant difference between RA and LA in analgesia requirements (5 vs. 8 paracetamol doses, p = 0.014; 2 vs. 10 tramadol doses, p = 0.042) as well as in the length of hospital stay (1.58 vs. 3.58 days, p = 0.038). CONCLUSIONS: RA may be associated with reduced postoperative pain and length of hospital stay. It is a valuable alternative to LA in smaller tumours where it may prove to be superior.

Resection of an elusive parathyroid adenoma in the aortopulmonary window.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcaemia and is caused by a single parathyroid adenoma in the neck in 85% or more of patients. National Institute for Health and Care Excellence (NICE) guidelines published in May 2019 advise that preoperative imaging is offered prior to parathyroid surgery for PHPT if it will inform surgical approach. If imaging, typically a neck ultrasound and a second modality that may use ionising radiation, does not identify the adenoma or is discordant, it is advised that surgery is performed by a surgeon with expertise in the management of unlocalised parathyroid disease.The cure rate in such cases is over 96%. Occasionally, however, PHPT cure can be challenging.A woman in her late 40s presented with bilateral renal calculi and was found to have PHPT. Following false positive imaging and three non-curative surgical procedures, removal of a supernumerary ectopic parathyroid adenoma in the aortopulmonary window via sternotomy achieved definitive cure.

Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma.

Primary aldosteronism (PA) is the most prevalent form of secondary hypertension and is most commonly caused by an adrenal adenoma or bilateral adrenal hyperplasia. Minimally invasive adrenalectomy is the treatment of choice for unilateral disease. Here, we report the case of a 57-year-old man with previous bladder cancer who was referred for evaluation of resistant hypertension and hypokalemia. Diagnostic workup indicated PA with computed tomography imaging revealing a left adrenal adenoma and adrenal venous sampling lateralizing to the left adrenal. He was therefore referred for a left adrenalectomy using a retroperitoneoscopic approach. However, surgery was complicated by significant perinephritis related to previous bladder cancer immunotherapy and, in view of an identifiable adrenal adenoma, a partial adrenalectomy was performed. Despite histology confirming removal of an adrenal adenoma, he remained hypertensive and hypokalemic with persistent PA. He underwent a computed tomography-guided percutaneous thermal (microwave) ablation of the residual adrenal nodule with immediate biochemical reversal of PA. Six years postprocedure, he remains biochemically and clinically cured from PA. This article presents the details of the case and reviews the literature on long-term outcomes for patients undergoing thermal ablation and adrenalectomy, suggesting that thermal ablation may be a viable alternative for selected patients.

Lymph node thyroglobulin in the diagnosis of metastases of thyroid carcinoma with the thyroid in situ: A prospective intraoperative study.

BACKGROUND: The use of thyroglobulin concentration in washout fluid of fine-needle aspiration (FNA-Tg) is a procedure advocated by international guidelines to diagnose metastatic LN in papillary thyroid cancer. With the increasing use of active follow-up or lobectomy alone for low-risk thyroid cancers, the determination of the diagnostic performance of FNA-Tg in the detection of metastatic PTC when the thyroid is in situ is paramount. MATERIALS AND METHODS: Prospective study with measurement of Tg in washout fluid obtained from intraoperative fine needle aspiration (FNA) cytology in order to avoid contamination from thyroid tissue and rigorously isolated punctured nodes. Receiver-operating characteristic (ROC) curve and area under the curve (AUC), optimal threshold to discriminate benign and malignant LN, sensitivity and specificity were provided. RESULTS: a total of 58 lymph nodes from 32 patients were analyzed. ROC analysis defined the optimal cutoff values of FNA-Tg at 60 ng/ml for the diagnosis of malignant LNs in patients with a thyroid in situ. Sensitivity and specificity were 75% (95% confidence interval 57.89-86.75) and 87.5% (95%CI: 69-95.66), respectively. CONCLUSION: Our results support the hypothesis that the Tg-FNA threshold for a safe diagnosis of LN metastasis in PTC is higher in presence of a thyroid gland in situ. The use of lower thresholds could result in false positive results and lead to unnecessary surgery.

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC. DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs. RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells. CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.