Non-functioning Adrenal Adenoma Research Articles

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 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 gm/cm2; 95% CI: -0.11, -0.03; p = 0.0004) and femoral neck (MD -0.05 gm/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 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 impact of adrenalectomy on kidney function in patients with NFA or MACS. Single-center cohort study of patients with NFA and MACS, 1999-2020. MACS was diagnosed based on post-dexamethasone cortisol (DST) ≥ 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 post-adrenalectomy 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/1.73m2, p < 0.001) 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, post adrenalectomy 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 pre-adrenalectomy eGFR and longer follow-up period. DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Both patients with 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.

Application of a Radiomics Machine Learning Model for Differentiating Aldosterone-Producing Adenoma from Non-Functioning Adrenal Adenoma.

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734-1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic-Radscore model had an AUC of 0.994 [95% CI, 0.978-1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma.

Impact of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512).

Epidemiology and Management of Hypertension and Diabetes Mellitus in Patients with Mild Autonomous Cortisol Secretion: A Review.

Mild autonomous cortisol secretion (MACS) is associated with a higher cardiometabolic risk than that observed in patients with nonfunctioning adrenal adenomas and in the general population. In patients with MACS, the excess of glucocorticoids affects various metabolic pathways, leading to different manifestations of metabolic syndrome and other comorbidities. Hypertension and diabetes mellitus are two of the most common cardiometabolic comorbidities associated with MACS, reaching a prevalence of up to 80% and up to 40%, respectively. In addition, they are the comorbidities that experienced a greater improvement after adrenalectomy in patients with MACS. Hypertension pathogenesis is multifactorial, including the coexistence of comorbidities such as obesity or diabetes and the role of the different polymorphisms of the glucocorticoid receptor gene, among others. Glucocorticoid-induced diabetes mellitus is mainly related to the detrimental effects of glucocorticoids on insulin-dependent glucose uptake in peripheral tissues, gluconeogenesis and insulin secretion. There are no specific recommendations for hypertension and diabetes treatment in patients with MACS. Thus, considering the similar underlying pathogenesis of hypertension and diabetes mellitus in overt and mild hypercortisolism, our recommendation is to follow this general stepwise approach: surgically remove the adrenal culprit lesion to induce remission from hypercortisolism; control hypercortisolism with steroidogenesis inhibitors; and treat elevated blood pressure or high glucose levels using carefully selected anti-hypertensives and glucose-lowering medications if blood pressure and glucose levels remain uncontrolled, respectively. In this review, we summarize the epidemiology, physiopathology and management of diabetes mellitus and hypertension in patients with MACS.

Cardiovascular Risk Markers in Adults With Adrenal Incidentaloma and Mild Autonomous Cortisol Secretion.

Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. Cross-sectional study. Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality.

FRI185 Post-adrenalectomy Improvement Of Kidney Function In Patients With Mild Autonomous Cortisol Secretion And Nonfunctioning Adrenal Adenoma

Abstract Disclosure: L. Rahimi: None. A. Kittithaworn: None. R. Gregg Garcia: None. J. Saini: None. P. Dogra: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Objective: Patients with mild autonomous cortisol secretion (MACS) have been reported to have a higher prevalence of chronic kidney disease (CKD), possibly due to the direct effect of hypercortisolism on kidney function and indirect effect of MACS-associated cardiovascular comorbidities, such as diabetes, hypertension, obesity, and dyslipidemia. Limited studies suggest improvement of kidney function following adrenalectomy in patients with MACS. In this study, we aimed to assess the factors associated and the degree and timing of change in kidney function post adrenalectomy in patients with MACS or nonfunctioning adrenal adenoma (NFA). Methods: We conducted a retrospective single-center study and included adult patients with MACS or NFA diagnosed based on a post-dexamethasone cortisol cutoff of 1.8 mcg/dL, who underwent adrenalectomy between 1999-2022. The change in estimated glomerular filtration rate (eGFR) before and up to 3.5 years after adrenalectomy was defined as the primary outcome. Demographics and comorbidities were included in univariable and multivariable analyses. Results: We included 155 (76.0%) patients with MACS and 49 (24.0%) patients with NFA treated with adrenalectomy. The proportion of women was high in both MACS and NFA (71.6% vs 69.4%, p=0.77), however, patients with MACS were older (median age 59.2 vs 54.6 years in NFA, p=0.05). The prevalence of hypertension was higher in MACS vs NFA (71.0% vs 53.1%, p=0.02), while the prevalence of diabetes (25.2% vs 28.6%, p=0.89), dyslipidemia (47.7% vs 46.9%, p=0.92), smoking (74.2% vs 68.9%, p=0.49) and obesity (median BMI 30.4 vs 31.8 kg/m2, p=0.35) was similar between the two groups. Prior to adrenalectomy, patients with MACS had lower eGFR (median 84.4 vs 89.2 ml/min/1.73m2, p=0.09) and a higher prevalence of CKD stage ≥ 3 (16.1% vs 8.2%, p= 0.16). In patients with MACS, after an initial decline of eGFR within 6 months post adrenalectomy (mean decrease 5.3 ml/min/1.73m2), eGFR increased by a mean of 4.9 points at 18-30 months, and by a mean of 8.1 points at 30-42 months post-adrenalectomy (p&amp;lt;0.01). Patients with NFA followed a similar eGFR change trend (p=NS). When comparing post-adrenalectomy delta eGFR in patients with MACS vs NFA, no significant differences were found. After adjusting for age, sex, pre-adrenalectomy eGFR, patient group, hypertension, antihypertensive therapy, and diabetes, there were still significant changes in eGFR over time. In a multivariable analysis, younger age (est -031, p&amp;lt;0.001) and lower pre-adrenalectomy eGFR (est-0.27, p=0.001) were associated with kidney function improvement post-adrenalectomy. Conclusion: Patients with MACS and NFA demonstrate improvement of eGFR over the 3.5 years of follow up post-adrenalectomy. The factors that are associated with improvement of eGFR are lower eGFR before surgery, younger age at time of adrenalectomy and longer follow up post adrenalectomy. Presentation: Friday, June 16, 2023

FRI184 Impact Of Adrenalectomy On Cognition In Patients With Mild Autonomous Cortisol Secretion

Abstract Disclosure: J. Saini: None. R. Nathani: None. C. Zhang: None. M. Suresh: None. K. Thangamuthu: None. S. Singh: None. V. Fell: None. E.J. Atkinson: None. S. Achenbach: None. N.H. Stricker: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have impaired cognition compared to patients with non-functioning adrenal adenomas. However, the impact of adrenalectomy on cognitive function in patients with MACS is unclear. Objective: To determine the impact of adrenalectomy on cognitive function in patients with MACS. Methods: Single-center prospective longitudinal study of adults with MACS. MACS was defined as serum cortisol &amp;gt;1.8 mcg/dL after the 1 mg dexamethasone suppression test (DST) in patients with adrenal adenomas without any overt features of hypercortisolism. Patients underwent cognitive evaluation using the standardized National Institute of Health (NIH) Toolbox Cognition Battery (7 tests of attention, episodic and working memory, language, executive function, cognitive flexibility, and processing speed) prior to adrenalectomy and at follow-up at least 10 months post-surgery. Fully corrected T-scores for age, sex, education, and race were compared using a paired t-test before and after adrenalectomy. A T-score of 50 is average performance (SD of 10). Total cognition is composite of fluid cognition (executive function, episodic memory, cognitive flexibility, working memory and processing speed) and crystallized cognition (language and vocabulary). Results: A total of 27 patients with MACS (median age 59.7 years, IQR 51.4-66.9, 17, 63% women) underwent cognitive evaluation prior to and at a median of 1.5 years (IQR, 1.1- 2.0) after adrenalectomy. Before surgery, median post-DST cortisol was 3.8 mcg/dL (IQR, 2.7-6.4) mcg/dL. Of the 27 patients, 21 (78%) patients developed post-operative adrenal insufficiency with 6 (21%) patients still requiring still requiring glucocorticoid replacement at the time of the last follow-up. At baseline, the mean total composite T-score was 50.7 (9.3), with fluid composite T-score of 49.9 (9.4) and crystallized composite T-score of 51.3 (8.7). Following adrenalectomy, all three composite T-scores improved compared to baseline. The crystallized composite T-score (composed of language and vocabulary) increased by a mean of 3.7 (5.5), P=0.001, the fluid composite T-score (composed of episodic, executive, working memory, cognitive flexibility, and processing speed) increased by a mean of 3.1 (8.3), P=0.068, and the total composite T-score improved by a mean of 3.9 (6.2), P=0.004. Conclusion: We showed that adrenalectomy in patients with MACS is associated with improvement in cognition. However, as test results may improve with practice (i.e., improvement due to taking the test the second time), to determine whether the improvements observed represent a reliable change in cognition, the next step is to evaluate for cognition score changes in referent subjects. Presentation: Friday, June 16, 2023

Do Non-Functional Adrenal Adenomas Affect Metabolic Profile and Carotid Intima-Media Thickness? A Single Centre Study from Poland.

Background: Compared to the general population, among people with adrenal incidentalomas (AIs) the diagnosis of obesity, hypertension, impaired carbohydrate and lipid metabolism is more common. The aformentioned disorders represent typical cardiovascular remodeling risk factors. The study was designed to assess the association between NFAIs, metabolic profile and carotid intima-media thickness (CIMT) as the predictive factor of atherosclerosis. Material: The study included 48 patients with NFAI (16 men, 32 women, mean age 58.6 +/- 9 years) and 44 control participants (15 men, 29 women, mean age 57 +/- 7 years). Both groups were matched for age, gender and BMI. Subjects with history of myocardial infarction, stroke or diabetes mellitus (DM) were excluded. Participants underwent adrenal imaging, biochemical evaluation, and measurement of CIMT. Hormonal evaluation was conducted in AI patients. Results: The NFAI group had significantly higher waist circumference (p < 0.01), higher systolic (p < 0.01) and diastolic blood pressure (p < 0.01), fasting insulin (p = 0.03) and glucose in the 2 h OGTT (p = 0.04) as well as higher CIMT (p < 0.01). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in this group as well. There was a positive correlation between CIMT and cortisol levels in 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). Conclusions: Patients diagnosed with NFAIs, despite normal cortisol inhibition in the 1 mg dexamethasone test, still presented a number of metabolic abnormalities. The assessment of IMT may proove valuable in indicate the presence of early vascular remodelling in asymptomatic patients. The underlying mechanisms of these findings are still unknown, hence further studies are required.

Mortality in Patients With Nonfunctional Adrenal Tumors

It is unclear if nonfunctional adrenal adenomas (NFAAs) are associated with increased mortality. To analyze mortality and causes of death in patients with NFAA. A national retrospective register-based case-control study was conducted and included 17 726 patients with a diagnosis of adrenal adenoma in Sweden from 2005 to 2019 who were identified and followed up until death or 2020 as well as 124 366 controls without adrenal adenoma. Individuals with diagnoses indicating adrenal hormonal excess or cancer were excluded. Follow-up started after 3 months of cancer-free survival following the date of the NFAA diagnosis. Sensitivity analyses were performed in subgroups of individuals for whom it was assumed that controls would also have undergone computed tomography: those with acute appendicitis (for whom it was assumed that there was no concern of cancer) and in patients with a combination of gallbladder, biliary tract, and pancreas disorders and 6-month and 12-month cancer-free survival following the date of the NFAA diagnosis. The data were analyzed in 2022. Diagnosis of NFAA. The primary outcome was all-cause mortality among patients with NFAA after adjustment for comorbidities and socioeconomic factors. Secondary outcomes were mortality due to cardiovascular diseases and cancer. Among 17 726 cases, 10 777 (60.8%) were women, and the median (IQR) age was 65 (57-73) years; among 124 366 controls, 69 514 (55.9%) were women, and the median (IQR) age was 66 (58-73) years. Among cases, overall mortality during the follow-up period (median, 6.2 years [IQR, 3.3-9.6 years]) was higher compared with controls (hazard ratio [HR] 1.43; 95 CI, 1.38-1.48; adjusted HR [aHR], 1.21; 95% CI, 1.16-1.26). The relative association of NFAA with overall mortality was similar in women and men (aHR, 1.22 [95% CI, 1.15-1.28] vs 1.19 [95% CI, 1.11-1.26]; P < .001 in both groups). In contrast, NFAA was associated with a larger increase in mortality among individuals younger than 65 years (aHR, 1.44; 95% CI, 1.31-1.58) than in older individuals (aHR, 1.15; 95% CI, 1.10-1.20; P < .001 for interaction). Mortality due to cardiovascular diseases was increased (aHR, 1.21; 95% CI, 1.13-1.29), as was mortality due to cancer (aHR, 1.54; 95% CI, 1.42-1.67). The association between NFAA and mortality remained significant and of similar magnitude in all sensitivity analyses. The results of this case-control study suggest that NFAA was associated with an increased overall mortality and mortality of cardiovascular disease and cancer. The increase was more pronounced among younger individuals.

Many Faces of Adrenal Lesions in a Large Patient Cohort: What Has Changed Over the Last Two Decades?

To review the presentation characteristics, clinical and hormonal evaluations, and histopathological results of patients with adrenal lesions over a 21-year period and evaluate the changes across the two decades. This single-center, retrospective study included 1003 patients with adrenal lesions who presented to our department between 2000 and 2021. Clinical, metabolic, hormonal, radiological, and pathological data of the patients were collected. Forty-seven percent of the lesions were non-functioning adrenal adenomas. Possible autonomous and autonomous cortisol secretion were detected in 22.2% of the patients. The percentages of the patients diagnosed with pheochromocytoma, primary hyperaldosteronism, adrenal Cushing syndrome, adrenocortical carcinoma, and adrenal metastasis were 7.4%, 4.8%, 4.7%, 0.9%, and 5.6%, respectively. Adrenalectomy was performed in 31.3% of the patients. Functional adrenal lesions were the leading cause of surgery (46.5%), followed by large size and/or suspicious imaging features (38.6%). Among the patients referred to surgery due to large size (≥6 cm), the diagnosis in 19% was metastasis, and in 12.1%, it was primary adrenocortical carcinoma. In patients with adrenal lesions with a size of 4-6 cm and suspicious imaging properties, the rates of metastasis and primary adrenocortical carcinoma were 44.4% and 4.8%, respectively. From the first to the second decade, major differences in presentation characteristics were increased detection of bilateral lesions and increased prevalence of possible autonomous and autonomous cortisol secretion. Adrenal lesions are common in the adult population, and while it is important to avoid overtreatment, hormone secretion, and malignancy should not be overlooked.

Mortality Not Increased in Patients With Nonfunctional Adrenal Adenomas: A Matched Cohort Study.

Mild autonomous cortisol secretion (MACS) is associated with increased mortality in patients with adrenal incidentalomas, but little is known regarding the potential risk associated with nonfunctional adrenal adenomas (NFAA), which constitute the majority of adrenal incidentalomas. Compare mortality risk in patients with NFAA, and different levels of MACS, to matched controls. This was a retrospective matched cohort study. All patients referred to 2 endocrine centers in southern Sweden because of an adrenal incidentaloma between 2005 and 2015 were enrolled. Controls (3:1) matched for sex, age, and residency were included. Primary endpoint was all-cause mortality. Outcome data were obtained from the Cause of Death Register. Patients were grouped according to cortisol level post 1-mg dexamethasone suppression test (cortisolDST) (<50 (NFAA), 50-82, 83-137, and ≥138 nmol/L). 1154 patients and 3462 matched controls were included. During a median follow-up of 6.6 years, 210 patients and 505 controls died. There were no statistically significant differences in mortality between patients with NFAA and their controls (HR 1.13 [0.87-1.46]) whereas mortality was increased compared to controls in patients with cortisolDST 83-137 (HR 1.99 [1.38-2.88]) and ≥138 nmol/L (HR 4.09 [2.41-6.93]). Likewise, the mortality risk was increased in patients younger than 65 years with cortisolDST 50-82 nmol/L compared with controls (HR 2.33 [1.30-4.17]). NFAA does not seem to pose a clinically relevant risk for increased mortality in patients with adrenal incidentalomas while patients with MACS, and especially younger patients and those with cortisolDST ≥83 nmol/L, have significantly increased mortality risk compared with matched controls.

PS-C21-4: EPIGENETIC ALTERATION OF 11B;-HYDROXYSTEROID DEHYDROGENASE 1 IN THE ADIPOSE TISSUE OF PATIENTS WITH ENDOCRINE HYPERTENSION

Objective: 11Beta-hydroxysteroid dehydrogenase 1 (11β;-HSD1) is a key enzyme involved in metabolic syndrome. The epigenetic control of 11β;-HSD1 is unclear. We examined the 11β;-HSD1 mRNA level and methylation status of the promoter region of the 11β;-HSD1 gene in the adipose tissue of patients with endocrine hypertension. Methods: We evaluated 8 adipose tissue specimens from patients with subclinical Cushing syndrome (SCS) due to cortisol-producing adenomas, 10 tissue specimens from patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). SCS and primary aldosteronism were diagnosed according to the guideline of the Japanese Endocrine Society. The mRNA level of 11β;-HSD1 was quantified using a real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific for the human 11β;-HSD1 promoter region. Results: The glycohemoglobin level was significantly higher in patients with SCS or APA compared with those with NFA (p &lt; 0.05). Blood pressure was significantly elevated in patients with APA compared with those with SCS or NFA (p &lt; 0.01). The 11β;-HSD1 mRNA level was significantly increased in the adipose tissues of SCS and APA compared with NFA patients (p &lt; 0.05). The methylation ratio was significantly lower in SCS compared with APA or NFA patients (p &lt; 0.05). Conclusion: 11β;-HSD1 gene expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological roles of epigenetic control of 11β;-HSD1 gene expression in adipose tissue requires further study.

Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and 10-year cardiovascular mortality based on the SCORE algorithm? A study from a single centre in Poland.

Adrenal incidentaloma (AI) secreting small amounts of glucocorticoids may cause morphological and functional changes in the blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with AI. But it is unclear whether the nonfunctional adrenal incidentalomas (NFAI) may also be a risk factor for cardiovascular diseases. The aim of this study was to determine the relationship between NFAI, carotid intima-media thickness (CIMT), and cardiovascular risk (CVR) based on Systematic Coronary Risk Evaluation (SCORE) prediction models for Europe. This study from a single centre in Poland included 48 NFAI patients and 44 individuals in the control group matched for age, sex, and body mass index (BMI). All participants underwent adrenal imaging, biochemical evaluation, measurement of CIMT, and assessment of the 10-year risk of cardiovascular mortality based on the SCORE algorithm. Hormonal evaluation was conducted in AI patients. The NFAI group showed significantly higher sodium (p = 0.02) and glucose levels in the 2-h oral glucose tolerance test (OGTT) (p = 0.04), a higher CIMT (p < 0.01), and a higher CVR calculated according to the SCORE algorithm (p = 0.03). The estimated glomerular filtration rate (eGFR) was higher in the NFAI group (p = 0.015). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in the NFAI group. Statistically significant positive correlations were found between CIMT and age (r = 0.373, p = 0.003), waist circumference (r = 0.316, p = 0.029), diastolic blood pressure (r = 0.338, p = 0.019), and CVR based on the SCORE algorithm (r = 0.43, p = 0.004). There was a statistically significant positive correlation between CIMT and serum cortisol levels after 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). Non-functional adrenal adenomas are associated with increased CIMT and CVR. Early stages of cardiovascular remodelling can be observed in asymptomatic NFAI patients.