Non-functioning Adrenal Adenoma Research Articles

A novel model using leukocytes to differentiating mild autonomous cortisol secretion and non-functioning adrenal adenoma

BackgroundMild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA).MethodsInthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden’s J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established.ResultsAfter propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%. In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively.ConclusionTheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.

8714 Impact of Adrenalectomy Versus Conservative Therapy On Frailty In Mild Autonomous Cortisol Secretion: A Prospective Multi-Center Cohort Study

Abstract Disclosure: M. Bassiony: None. P. Dogra: None. L. Šambula: None. J. Saini: None. U. Ambroziak: None. D. Kastelan: None. I. Bancos: None. Background: Frailty is characterized by a multi-system decline and increased vulnerability to adverse health outcomes. We have recently shown that patients with mild autonomous cortisol secretion (MACS) demonstrate a higher prevalence of frailty compared to patients with nonfunctioning adrenal adenomas (NFA). Objective: To determine the impact of adrenalectomy versus conservative management in patients with MACS, as compared to patients with NFA. Design: Multi-center, prospective cohort study (2019-2023). Methods: Adults with NFA and MACS were assessed for frailty at baseline and 1-year post-adrenalectomy, or conservative follow up. Frailty was assessed by frailty index (FI) that encompasses 47 health variables (comorbidities, symptoms, daily living activities). Patients with FI >0.25 were classified as frail. MACS was defined as post-dexamethasone cortisol>1.8 mcg/dL. Results: Paired frailty assessments were performed in 226 patients (MACS:117 and NFA:109). At baseline, patients’ median age was 63 years (interquartile range, IQR 55-78) and 113 (50%) were women, without differences between patients with MACS vs NFA. In conservatively treated patients with NFA (n=106) and MACS (n=61), baseline FI (median 0.15 vs 0.16, p=0.190) and frailty prevalence (18% vs 20%, p=0.846) were similar between groups. At follow up, patients with MACS demonstrated an increase in FI (mean of 0.013 vs -0.018 in patients with NFA, p=0.009). In conservatively treated patients, and after excluding outliers, post-dexamethasone cortisol positively correlated with a higher delta FI at follow up (estimate 0.015, p=0.01). Compared to conservatively treated, patients with MACS treated with adrenalectomy (n=56) were younger (median age of 58 vs 67 years, p=0.0002), had a similar post-dexamethasone cortisol (median 3.4 vs 2.8 mcg/dL, p=0.853), a higher FI (median 0.26 vs 0.15, p value <0.0001) and frailty prevalence (52% vs 20% P=0.0003) at baseline. At follow up, patients with MACS treated with adrenalectomy showed improved FI when compared to conservatively treated (mean delta FI of -0.025 vs 0.014, p=0.017). Conclusions: Patients with MACS treated conservatively demonstrate an accelerated frailty when compared to patients with NFA. In contrast, frailty improves in patients with MACS treated with adrenalectomy. Presentation: 6/2/2024

6999 Utilizing Machine Learning for One-Step Diagnosis Of Adrenal Diseases: Integrating Clinical, Serum Steroid, And Body Composition Data

Abstract Disclosure: S. Park: None. J. Noh: None. J. Kim: None. T. Kim: None. H. Seo: None. J. Choo: None. M. Choi: None. J. Kim: None. Background: With the increasing incidence of adrenal incidentalomas, the precise diagnosis of subtypes, such as mild autonomous cortisol secretion (MACS), adrenal Cushing’s syndrome (ACS), primary aldosteronism (PA), pheochromocytoma and paraganglioma (PPGL), or nonfunctioning adrenal adenomas (NFA) is becoming more critical. However, the process of making accurate diagnoses remains intricate and challenging. This study aims to explore a streamlined, one-step method for diagnosing adrenal nodules, employing a machine learning (ML) model that integrates clinical data (CL), serum steroid profiles (SSP), and computed tomography-based body composition data (BC). Methods: We utilized ML models for subtyping adrenal diseases within a cohort of 641 patients (comprising MACS=141, ACS=64, PA=265, PPGL=78, and NFA=93), incorporating 37 CL, 64 SSP, and 15 BC features. Patients were randomly split into training and test cohorts at a 4:1 ratio, with each disease proportionally represented. The ML-based pipeline involved ML model selection, outlier detection, feature selection, and re-sampling algorithm. An ML model was developed to classify each of the five distinct adrenal diseases individually. In addition, separate ML models were also developed and optimized for individual comparisons between NFA and each of the other four diseases. The performance was evaluated using balanced accuracy, sensitivity, specificity, area under the curve (AUC), and F1 score. Results: The OneVsRest Classifier exhibited the best performance in the multi-class classification of the five adrenal diseases, achieving a balanced accuracy (0.78), sensitivity (0.77), specificity (0.93), and an AUC of 0.89. In this process, 10 CL features and 39 SSP features were utilized, whereas BC did not yield significant features. Using only SSP, the ML model achieved a balanced accuracy of 0.71 and an AUC of 0.89, whereas the ML model using only CL demonstrated a relatively lower accuracy of 0.58 and an AUC of 0.82. In models comparing MACS, ACS, PA, and PPGL with NFAs, the accuracies were 0.85, 0.94, 0.78, and 0.86, respectively, with AUCs of 0.96, 0.99, 0.90, and 0.94, respectively. The ML model differentiating between NFA and the other functioning adrenal diseases exhibited an accuracy of 0.75 and an AUC of 0.79 Conclusion: We have developed a highly sensitive and specific one-step ML model for differentiating adrenal diseases using CL, SSP, and BC. This approach is anticipated to facilitate precise diagnoses of adrenal nodules, thereby enhancing patient care and improving clinical outcomes. Presentation: 6/2/2024

6425 Impact Of Adrenalectomy On Mood, Sleep, And Quality Of Life In Patients With Mild Autonomous Cortisol Secretion: A Prospective Longitudinal Study

Abstract Disclosure: J. Saini: None. V. Fell: None. B. Atkinson: None. S. Achenbach: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have an impaired quality of life and a higher prevalence of sleep and mood disturbances as compared to patients with nonfunctioning adrenal adenomas. The impact of adrenalectomy on quality of life, mood, and sleep is unclear. Objective: To determine the impact of adrenalectomy on quality of life, sleep, and mood in patients with MACS Methods: We conducted a single-center prospective longitudinal study of adults with MACS scheduled for adrenalectomy and referent subjects evaluated between 2018 and 2023. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Patients and referent subjects had a baseline and a follow-up evaluation at least 10 months later. Differences were assessed using paired t-tests for (1) Quality of life using Short Form-36 (SF 36) survey (Physical and Mental component summary score), sex and age-adjusted (2) Mood using Beck’s Depression Inventory (BDI) (3) Sleep using Pittsburgh Sleep Quality Index (PSQI). Results: We evaluated 41 patients before and after adrenalectomy, and 31 referent subjects at baseline and follow-up visit, at a similar interval (median 1.6, IQR 1.2-2.0 vs 1.5 years, IQR 1.0-2.2, P=0.759). While sex distribution was similar between the groups (66% vs 84% women, P=0.086), patients with MACS were older than the referent group (median age 57.3, IQR 48.8-66.9 vs 49.0, IQR 41.7-57.9 years, P=0.005). After adrenalectomy, patients improved their mood with a mean decrease of -4.71 (SD: 9.11), P=0.002 on the BDI questionnaire. Patients also demonstrated improvement in the SF-36 mental component score by a mean of 6.48 (SD: 10.97), P<0.001. While the overall SF36 physical component score did not improve after adrenalectomy (1.953 (SD: 11.02), P=0.269), one of the PCS components, role-physical limitation, increased by a mean of 6.25 (SD: 13.03). Patients reported better sleep with PSQI score decreasing by a mean of -2.59 (SD: 3.64), P<0.001. No differences in BDI, SF36, and PSQI were observed between baseline and follow-up in referent subjects. Conclusions: After adrenalectomy, patients with MACS showed an improvement in sleep, mood, and mental component of quality of life. Presentation: 6/3/2024

12529 Pre And Post-operative Evaluation And Outcomes After Adrenalectomy At A Tertiary Referral Center

Abstract Disclosure: C. Hung: None. L.M. Fishbein: None. M.R. Clay: None. M.B. Albuja-Cruz: None. C. Raeburn: None. K. Kiseljak-Vassiliades: None. M.E. Wierman: None. Introduction: The prevalence of adrenal nodules has increased over time due to increased abdominal CT imaging. Laboratory evaluation to screen for hypercortisolism, primary aldosteronism, or pheochromocytoma is recommended depending on nodule appearance and clinical risk factors. Our aim was to retrospectively determine the preoperative hormonal workup prior to adrenalectomy and to identify the postoperative comorbidities as they relate to preoperative hypercortisolism. Methods: From May 2017-March 2023, 205 adrenalectomies were performed for adrenal nodules. Preoperative and postoperative comorbidities, medications, laboratory results, imaging and pathology were assessed up to 1 year post surgery. Patients were stratified by degree of hypercortisolism, based on 1 mg dexamethasone suppression test, into cortisol 1.8-5 μg/dL (DST 1.8-5) or cortisol >5 μg/dL (DST >5). Statistical analysis included Fischer’s exact test and two-sample proportion test. Results: Of 205 adrenalectomies, 51 patients had primary aldosteronism (24.9%), 51 had pheochromocytoma (24.9%), 23 had ACC (11.2%), 15 had non-functional adrenal adenomas (7.3%), and 65 had adenomas associated with hypercortisolism (31.7%)—42 with DST 1.8-5 (20.5%), 23 with DST >5 (11.2%). Preoperatively 9 (17.6%) patients with PA underwent 1 mg DST, while 54 (83.1%) patients with hypercortisolism (DST >1.8) had aldosterone measured. Overall, 183/205 patients (89.3%) had hypertension preoperatively. Of the patients with hypercortisolism (DST>1.8), 58 (89.2%) had hypertension, without a difference in prevalence between DST 1.8-5 and DST >5 groups. For those with abnormal DST, no significant reduction in hypertension was observed within 2 months following adrenalectomy, but at 1 year postop, prevalence was reduced (89.2% preop vs 71.9% postop, p=0.03). There was no significant reduction in the prevalence of type 2 diabetes (p=0.78), prediabetes (p=0.48), hyperlipidemia (p=0.33), osteoporosis (p=0.53), or osteopenia (p=0.67) at 1 year postop in those with hypercortisolism. After adrenalectomy, 42.9% patients in the DST1.8-5 and 73.9% in the DST >5 group were discharged on glucocorticoids. Many patients were lost to long-term follow up. In those remaining, at 1 year postop, 14.3% patients in the DST1.8-5 and 50% in the DST >5 group still required steroids for adrenal insufficiency. Conclusions Not all patients with adrenal nodules are being screened for excess hormone production. Hypercortisolism is prevalent in patients undergoing adrenalectomy. Preoperative workup is essential to identify these patients before surgery as adrenal insufficiency can persist postoperatively. Adrenalectomy for hypercortisolism is associated with a reduction in hypertension at 1 year postoperatively. Presentation: 6/3/2024

6427 Impact of Adrenalectomy On Frailty And Muscle Function In Patients With Mild Autonomous Cortisol Secretion: A Prospective Longitudinal Study

Abstract Disclosure: J. Saini: None. V. Fell: None. B. Atkinson: None. S. Achenbach: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have a higher prevalence of frailty and reduced muscle strength as compared to patients with nonfunctioning adrenal adenomas or subjects without adrenal disorders. Objective: To determine the impact of adrenalectomy on frailty and parameters of functional strength in patients with MACS. Methods: We conducted a single-center prospective longitudinal study of adults with MACS scheduled for adrenalectomy and referent subjects evaluated between 2018 and 2023. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Patients and referent subjects had a baseline and a follow-up evaluation at least 10 months later. Differences were assessed using paired t-tests for (1) Frailty Index (FI)--calculated using a questionnaire containing 47 variables on comorbidities, symptoms, and daily living activities (frailty defined as FI>0.25) (2) physical function assessed using handgrip strength (Jamar Plus digital hand dynamometer), timed up-and-go test (time taken to rise from a chair, walk to and from 3 m, and sit down), gait speed, 6-minute walk test, and (3) Advanced Glycation End (AGE) Product (using AGE reader). Results: We evaluated 41 patients before and after adrenalectomy, and 31 referent subjects at baseline and follow-up visit, at a similar interval (median 1.6, IQR 1.2-2.0 vs 1.5 years, IQR 1.0-2.2, P=0.759). While sex distributions were no different between the 2 groups (women, 66% vs 84%, P=0.086), patients with MACS were older than the referent group (median age 57.3, IQR 48.8-66.9 vs 49.0, IQR 41.7-57.9 years, P=0.005). Post-adrenalectomy, FI decreased by a mean of 0.057 (SD 0.08), P<0.001 in patients, and remained unchanged in the referent group. AGE decreased in patients by 0.148 (SD 0.45), P=0.04 but not in referent subjects (-0.047, SD 0.242, P=0.5). Patients demonstrated no improvement in parameters of muscle strength: gait speed (mean change 0.305 m/s, P=0.453), 6-minute walk test (mean change 16.4 meters, P=0.201), dominant (mean Z score change -0.055, P=0.72) and nondominant (mean Z score change -0.199, P=0.192) hand grip muscle strength. At follow-up, both patients (mean change 1.897 seconds, P<0.001) and referent subjects (mean change=1.475 seconds, P<0.001) demonstrated a deterioration on the timed up-and-go test. Conclusions: While no improvement was seen in the parameters of muscle strength, adrenalectomy improved the frailty index in patients with MACS. In addition, AGE, a biomarker associated with cardiovascular morbidity, decreased after adrenalectomy, suggesting a beneficial cardiovascular impact of MACS reversal. Presentation: 6/1/2024

Could CT Radiomic Analysis of Benign Adrenal Incidentalomas Suggest the Need for Further Endocrinological Evaluation?

We studied the application of CT texture analysis in adrenal incidentalomas with baseline characteristics of benignity that are highly suggestive of adenoma to find whether there is a correlation between the extracted features and clinical data. Patients with hormonal hypersecretion may require medical attention, even if it does not cause any symptoms. A total of 206 patients affected by adrenal incidentaloma were retrospectively enrolled and divided into non-functioning adrenal adenomas (NFAIs, n = 115) and mild autonomous cortisol secretion (MACS, n = 91). A total of 136 texture parameters were extracted in the unenhanced phase for each volume of interest (VOI). Random Forest was used in the training and validation cohorts to test the accuracy of CT textural features and cortisol-related comorbidities in identifying MACS patients. Twelve parameters were retained in the Random Forest radiomic model, and in the validation cohort, a high specificity (81%) and positive predictive value (74%) were achieved. Notably, if the clinical data were added to the model, the results did not differ. Radiomic analysis of adrenal incidentalomas, in unenhanced CT scans, could screen with a good specificity those patients who will need a further endocrinological evaluation for mild autonomous cortisol secretion, regardless of the clinical information about the cortisol-related comorbidities.

Assessment of aortic perivascular and renal sinus fat in endogenous cortisol excess of different etiology.

Endogenous cortisol excess is known to affect body fat distribution. Ectopic fat is the accumulation of triglycerides in non-adipose tissue regions that normally contain little fat. The aim of study was to investigate the amount of ectopic fat in aortic perivascular and renal sinus fat of patients with endogenous cortisol excess and its relationship with their comorbitidies and laboratory findings. A total of 119 patients, including 16 patients with pituitary Cushing's disease (CD), 21 patients with adrenal Cushing's syndrome (CS), 34 patients with mild autonomous cortisol secretion (MACS), and 48 patients with nonfunctioning adrenal adenomas were enrolled in this retrospective study. Aortic perivascular fat and renal sinus fat were evaluated with magnetic resonance imaging. It was determined that the amount of aortic perivascular fat was increased in patients with CD (P = 0.01). The linear regression analysis showed that the amount of perivascular fat was associated with triglyceride levels and cortisol levels after the 1mg dexamethasone suppression test as well as with gender (P < 0.01). Renal sinus fat measurements were similar in the groups (P > 0.05). After adjusting for age, sex, and BMI, perivascular fat was found to be higher in pituitary the CD than in the MACS and the nonfunctioning adenoma groups, and renal sinus fat was seen to be higher in pituitary the CD than in the MACS groups (P < 0.05). Patients with diabetes mellitus had an increased amount of renal sinus fat (P = 0.008). The amount of perivascular and renal sinus fat may increase in patients with CD. Further studies are needed to elucidate ectopic fat distribution in patients with endogenous cortisol excess.

Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS.

Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing's syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear. To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function. We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment. Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group. Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

Assessment of the diagnostic efficacy of radiological and functional evaluation of primary adrenal mass and its' surgical outcomes.

Objective of this study was to assess the diagnostic efficacy of the most commonly used radiological evaluation in form of contrast enhanced computed tomography of abdomen with adrenal protocol, basic functional evaluation and surgical outcomes of primary adrenal masses. We have retrospectively analysed the institutional records of 108, patients admitted from August 2017 to September 2023, who had underwent surgical intervention for their adrenal mass after thorough evaluation and stabilization. Flank pain was the most common symptoms in 44 (40.74%) patients. Non-functional adrenal adenoma was found in 36 (33.33%) patients. Pheochromocytoma was the most the common functional adrenal mass found in 24 (22.22%) patients. CECT abdomen had suggested features of malignancy in 16(14.81%) patients. In final histopathological report 26(24.07%) patients had pheochromocytoma and 12 (11.11%) patients had adrenocortical carcinoma. CECT abdomen had sensitivity of 75%, specificity of 95.6%. Plasma free metanephrines and normetanephrine analysis had shown sensitivity of 90%, specificity of 92.86%, aldosterone to renin ratio had sensitivity of 92%, specificity of 100%. Sensitivity and specificity of the low-dose dexamethasone suppression test and plasma dehydroepiandrosterone was 100% in our study. Eighty patients (74.07%) were operated with laparoscopic adrenalectomy, 20 (18.52%) patients with open adrenalectomy. Eight patients (7.41%) were converted from laparoscopic to open. Laparoscopic approach had significantly lesser mean operating time, lesser blood loss, lesser hospitalization and lesser post-operative complications. Radiological analysis and functional analysis has shown good sensitivity and high specificity. Laparoscopic approach has advantage of lesser operative time, lesser hospitalization and lesser post-operative complications.

Cognitive functions and the brain-derived neurotrophic factor in patients with mild autonomous cortisol secretion.

The impact of abnormal cortisol secretion on cognitive functions in patients with mild autonomous cortisol secretion (MACS) remains uncertain. To assess cognitive functions, determine serum brain-derived neurotrophic factor (BDNF) concentration in patients with MACS, and investigate the association between cognitive subdomains and BDNF. We prospectively recruited 84 participants-28 patients with MACS, 28 patients with nonfunctional adrenal adenoma (NFAA), and 28 control subjects matched for age, gender, body mass index (BMI), visceral adiposity, and educational level. The serum BDNF concentration of participants was measured. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-focused interviews and Montreal Cognitive Assessments (MoCA) were carried out by an experienced psychiatrist. Patients with MACS had a higher serum BDNF concentration than the NFAA (P = .001), while that of patients with NFAA was lower than the controls (P = .044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (P < .05). No significant difference was found in MoCA scores between MACS and NFAA groups (P = .967), whereas those were lower than the control group (P = .004). When the cognitive subdomains were examined separately, MACS group performed higher memory score than NFAA (P = .045), but lower language scores than both the NFAA (P = .024) and control groups (P < .001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, P = .002), whereas DST was negatively correlated with language score (r = -0.355, P = .008). Low-grade hypercortisolism is associated with elevated BDNF concentrations, which may be a protective factor for memory function in patients with MACS relative to those with NFAA.

Multimodal integration of radiology and pathology signatures for distinguishing between aldosterone-producing adenomas and nonfunctional adrenal adenomas.

To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000). A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.

Fracture risk and bone health in adrenal adenomas with mild autonomous cortisol secretion/subclinical hypercortisolism: a systematic review, meta-analysis and meta-regression.

Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome, glucocorticoid-induced osteoporosis, and fractures. In this background, the present systematic review and meta-analysis aimed to collate the available evidence and provide a summary of the effect of MACS/SH on bone health in terms of fractures, osteoporosis/osteopenia, microarchitecture, and bone turnover. PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched for observational studies reporting prevalence of fractures, osteoporosis/osteopenia or data on bone microarchitecture/bone turnover markers (BTMs). Following literature search, 16 observational studies were included. Pooled prevalence of any fractures (vertebral and non-vertebral), vertebral fractures, and osteoporosis/osteopenia in MACS/SH were 43% [95% confidence intervals (CI): 23%, 62%], 45% (95% CI: 22%, 68%) and 50% (95% CI: 33%, 66%), respectively. On meta-regression, age, sex, 24-hour urinary free cortisol, and dehydroepiandrosterone-sulfate did not predict fracture risk. The likelihood of any fractures [odds ratio (OR) 1.61; 95% CI: 1.18, 2.20; P = 0.0026], vertebral fractures (OR 2.10; 95% CI: 1.28, 3.45; P = 0.0035), and osteoporosis/osteopenia (OR 1.46; 95% CI: 1.15, 1.85; P = 0.0018) was significantly higher in adrenal adenomas and MACS/SH than non-functional adrenal adenomas. Subjects with MACS/SH had significantly lower bone mineral density (BMD) at lumbar spine [mean difference (MD) -0.07 g/cm2; 95% CI: -0.11, -0.03; P = 0.0004) and femoral neck (MD -0.05 g/cm2; 95% CI: -0.08, -0.02; P = 0.0045) than their non-functional counterparts. Limited data showed no significant difference in BTMs. Publication bias was observed in the pooled prevalence of any fractures, vertebral fractures and pooled MD of femoral neck BMD. To conclude, people with adrenal adenomas/incidentalomas and MACS/SH are at a 1.5- to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non-functional adrenal adenomas and should routinely be screened for bone disease. Nevertheless, considering the modest sample size of studies and evidence of publication bias, larger and high-quality studies are required (CRD42023471045).

Liver mass masquerading as adrenal space-occupying lesion: A rare presentation

Adrenal pseudotumors have been described in the literature; however, liver mass masquerading as adrenal space occupying lesion is a rare entity. Here, we describe the case of a 40-year-old female who presented with right-sided abdominal pain for 1 year and was provisionally diagnosed as non-functioning adrenal adenoma after evaluation. She was planned for laparoscopic adrenalectomy. On laparoscopy, a mass arising from the liver was found. The procedure was abandoned and a computed tomography-guided tru-cut biopsy of liver mass was done, which showed the feature of benign liver tissue suggestive of hepatic adenoma. Later, she underwent an excision of the liver mass. Adrenal pseudotumor should always be kept in mind during surgery for any suspected adrenal mass.

Clinical, Biochemical, and Radiological Retrospective Analysis in Patients with Adrenal Incidentaloma – A Secondary Publication

Objective: To evaluate the epidemiological, demographic, clinical features, treatment approaches, and survival of patients followed up for adrenal incidentaloma. Methods: Data from 46 patients who were treated and followed up due to adrenal incidentaloma in the Endocrinology Department of Mersin University Health Research and Application Hospital between 2010 and 2014 were retrospectively analyzed. Results: Of the cases included in the study, 13 were male, 33 were female, and the mean age was 54.09 ± 10.7 years. The most common reason for admission was abdominal pain in 34.78% of the patients, the most commonly diagnosed radiological method was dynamic adrenal CT in 60.87%, and the most common location was the left adrenal gland. The mean lesion diameter was between 26.8 ± 16.5 mm. The frequency of hypertension was 50%, obesity 47.8%, type 2 diabetes 21.7%, osteoporosis 42.8%, and metabolic syndrome 41.3%. According to hormonal evaluation results, non-functional adrenal adenoma (NFAA) was found in 82.61%, subclinical Cushing’s syndrome (SCS) in 15.21%, and aldosteronoma in 2.1%. Myelolipoma, pheochromocytoma, and adrenocortical adenoma were diagnosed in 8 cases undergoing adrenalectomy. One patient died due to liver failure. No hormonal activation or growth in lesion size was detected during the follow-up of the patients. Conclusion: Due to the very different pathological and radiological appearances of adrenal incidentaloma, it is important to evaluate demographic, etiological, clinical, laboratory, and radiological data as a whole in the treatment and follow-up.

Adrenal Incidentaloma Prevalence and Clinical Management- A Retrospective Study

This study aims to investigate the characteristics and prevalence of adrenal incidentalomas and subsequent clinical practice among patients in Armed Forces Hospital Southern Region -Saudi Arabia, 2021. An observational retrospective study was conducted in Armed Forces Hospital Southern Region -Saudi Arabia on the medical records of 383 consecutive patients. Patients with incidental adrenal tumors who underwent abdominal CT scans with intravenous contrast during the period from January 2013 and December 2021. A total of 300 patients were included in this study. However, the data were analyzed using statistical tests. The results revealed that most patients with adrenal incidentalomas were above 60 (53.3%%). The gender distribution was nearly equal, with 50.3% females and 49.7% males. Most observed tumors were unilateral (96.0%), while a small percentage was bilateral (4.0%). In terms of size, the majority were less than 1 cm (59.0%), followed by sizes greater than 4 cm (31.0%) and 1-4 cm (10.0%). Further analysis indicated that 49.3% were found to have functioning tumors, while 50.7% had non-functioning tumors. The specific types of functioning tumors included non-functioning adrenal adenoma (50.7%), pheochromocytoma (16.9%), Cushing’s syndrome (5.8%), and other functional tumor types (28.0%). Most of these patients were not referred to endocrine clinics. Adrenal incidentalomas are prevalent in the above-60 age group, with most tumors being non-functional. Further research into adrenal incidentalomas associated with diabetes and hypertension is required.

O-05 A novel mutation of MEN1 gene in familial Multiple Endocrine Neoplasia Type 1 (MEN1): A report of two cases

Abstract Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare (1-9/100000) autosomal dominant disease. It is characterized by primary hyperparathyroidism (90%), enteropancreatic tumor (60-70%), non-functional adrenal adenomas (30%) and pituitary tumors (10-20%). Herein, we present two cases in the same family with MEN1 syndrome caused by a novel mutation. Clinical Case 1: 49-year-old male presented to our clinic with fasting hypoglycemia. Fasting serum glucose (FSG) was 51 mg/dl and serum cortisol was 18 ug/dl. During the hypoglycemia in prolonged fasting test, the serum levels of glucose, insulin and C-peptide were 37 mg/dl, 17.3 mu/l, 7.75 ng/ml respectively (Table 1). Abdominal MRI revealed mass lesions in the pancreas (Figure 1). Ultrasonography of the neck and MIBI scintigraphy performed because of the high levels of calcium and parathyroid hormone (PTH), were consistent with parathyroid adenoma (Table 2). Pituitary MRI showed a 12 mm macroadenoma. He underwent parathyroidectomy and distal pancreatectomy simultaneously. The resected specimens revealed a well-differentiated neuroendocrine tumor (NET) of the pancreas and parathyroid adenoma. The patient had no new hypoglycemic episodes after surgery and serum calcium remained within the normal range (Table 2). Central hypothyroidism and hypogonadotropic hypogonadism which was resulted from the pressure of the adenoma was managed medically. Genetic testing revealed a heterozygous mutation in NM_001370251.1:c.949del(HET). First degree relatives of the patient were screened for MEN. Clinical Case 2: The son of case 1, an 18-year-old male, presented with fasting hypoglycemia. He had a BMI of 37 kg/m2 and underwent gastric botox 3 months prior to his presentation. FPG was 52 mg/dl and serum cortisol was 20 ug/dl. Prolonged fasting test confirmed the diagnosis of insulinoma (Table 1). Abdominal MRI showed a pancreatic tail mass 37×22 mm in size. Gallium 68 PET/CT DOTATATE revealed increased uptake in multiple lesions in the pancreas. Ultrasonography and MIBI scintigraphy showed a parathyroid adenoma. A nonfunctional microadenoma was detected in pituitary MRI. The patient underwent distal pancreatectomy. Following pancreatectomy, right superior and left inferior parathyroidectomies were performed. Since his serum calcium levels started to increase in 48 hours after the operation, the patient has had second operation for left superior parathyroidectomy. After the operation, the serum calcium and parathyroid hormone levels were 9.2 mg/dl, 58 pg/ml respectively. Specimens revealed well-differentiated NET and atypical parathyroid adenoma. The patient was found to have the same genetic mutation with his father and during the follow up the serum glucose and calcium levels remained within the normal range (Table 2). Conclusion In the genetic examination the heterozygous mutation NM_001370251.1:c.949del(HET) in exon 7/11 of the MEN1 gene found in our patients represents a novel mutation.Figure 1.MRI showing pancreatic masses Table 1.Laboratory findings Table 2.Prolonged fasting test

Epigenetic alterations of 11beta-hydroxysteroid dehydrogenase 1 gene in the adipose tissue of patients with primary aldosteronism.

11Beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) is a key enzyme involved in metabolic syndrome. Transcript-specific epigenetic regulation of the gene encoding 11β-HSD1 (HSD11B1) has been reported. We examined the mRNA level and methylation status of the HSD11B1 promoter region in the adipose tissue of patients with primary aldosteronism (PA). We compared 10 tissue specimens from patients with PA caused by aldosterone-producing adenoma (APA) with 8 adipose tissue specimens from patients with subclinical Cushing's syndrome (SCS) caused by cortisol-producing adenomas, 4 tissue specimens from patients with Cushing's adenoma (Cu), or 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). PA, SCS, and Cu were diagnosed according to the guideline of the Japan Endocrine Society. The mRNA level of HSD11B1 was quantified using real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific to the human HSD11B1 promoter region. The glycohemoglobin level was significantly higher in patients with APA, SCS, or Cu than in those with NFA (p < 0.05). Blood pressure was significantly higher in patients with APA than in those with SCS, Cu, or NFA (p < 0.01). The HSD11B1 mRNA level was significantly increased in the adipose tissues of APA or SCS patients compared with Cu or NFA patients (p < 0.05). The methylation ratio was significantly lower in SCS patients than in APA, Cu, or NFA patients (p < 0.05). HSD11B1 expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological role of epigenetic regulation of HSD11B1 expression in adipose tissue requires further study.

Kidney Function in Patients With Adrenal Adenomas: A Single-Center Retrospective Cohort Study.

Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P < .001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy.

Can MDCT Enhancement Patterns Be Helpful in Differentiating Secretory from Non-Functional Adrenal Adenoma?

Background and Objectives: Primary adrenal tumors (AT) are a heterogeneous group of neoplasms due to their functional heterogeneity, which results in the diverse clinical presentation of these tumors. The purpose of this study was to examine cross-sectional imaging characteristics using multi-detector computed tomography (MDCT) to provide insight into the lesion characterization and functional status of these tumors. The radionuclide imaging using Technetium-99m radiolabeled hydrazinonicotinylacid-d-phenylalanyl1-tyrosine3-octreotide (99mTc-HYNIC-TOC), was also used in the diagnostic evaluation of these tumors. Materials and Methods: This cross-sectional study included 50 patients with confirmed diagnoses of AT (21 hormone-secreting and 29 non-functional) at the University Clinical Center, Kragujevac, Serbia, during the 2019-2022 year period. The morphological and dynamic characteristics using MDCT were performed, using qualitative, semi-quantitative, and quantitative analysis. Absolute washout (APW) and relative washout (RPW) values were also calculated. A semi-quantitative analysis of all visual findings with 99mTc-HYNIC-TOC was performed to compare the tumor to non-tumor tracer uptake. Results: A statistically significant difference was found in the MDCT values in the native phase (p < 0.05), the venous phase (p < 0.05), and the delayed phase (p < 0.001) to detect the existence of adrenal tumors. Most of these functional adrenocortical lesions (n = 44) can be differentiated using the delayed phase (p < 0.05), absolute percentage washout (APW) (p < 0.05), and relative percentage washout (RPW) (p < 0.001). Furthermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumor existence (p < 0.001). There is a positive correlation between radionuclide imaging scan and APW to detect all AT (p < 0.01) and adrenocortical adenomas as well (p < 0.01). Conclusions: The results can be very helpful in a diagnostic algorithm to quickly and precisely diagnose the expansive processes of the adrenal glands, as well as to learn about the advantages and limitations of the mentioned imaging modalities.