Autonomous Cortisol Secretion Research Articles

In patients with mild autonomous cortisol secretion adrenalectomy improves the control of body weight, blood glucose levels and blood pressure : Results of a controlled randomized study

In patients with mild autonomous cortisol secretion adrenalectomy improves the control of body weight, blood glucose levels and blood pressure : Results of a controlled randomized study

Mild Autonomous Cortisol Secretion (MACS) - Related Osteoporosis.

Mild autonomous cortisol secretion (MACS) has thus far been associated with several comorbidities, among which osteoporosis and fractures appear to be highly prevalent. Recent guidelines for adrenal incidentalomas have updated the definition of MACS, currently formulated on serum cortisol after a 1-mg dexamethasone test above 1.8 µg/dL or 50 nmol/L. Previous studies on bone health in adrenal incidentalomas had adopted different definitions of MACS, which produced heterogenous results in terms of fracture prevalence. This review aims to summarize the clinical impact of MACS in relation to fractures, bone quantity and quality, by providing a thorough update on MACS-related osteoporosis (MACS-ROP). Room for research in this area is large, and management of this comorbidity still needs to be elucidated.

Are comorbidities of patients with adrenal incidentaloma tied to sex?

A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up. We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months. The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p<0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p<0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sex-related pattern was observed. Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.

Long term management of adult bilateral adrenal hyperplasia with mild autonomous cortisol secretion - data from a Romanian tertiary center

Long term management of adult bilateral adrenal hyperplasia with mild autonomous cortisol secretion - data from a Romanian tertiary center

Cognitive functions in patients with mild autonomous cortisol secretion: Is it related with the serum brain-derived neurotrophic factor level?

Cognitive functions in patients with mild autonomous cortisol secretion: Is it related with the serum brain-derived neurotrophic factor level?

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).

EXPLORATION OF SCREENING FOR PRIMARY ALDOSTERONISM BY IMMUNOHISTOCHEMISTRY IN PATIENTS WITH ADRENAL SURGERY IN CHINESE

Objective: Primary aldosteronism (PA) is common secondary hypertension, however, the screening rate for PA is not entirely satisfactory. This study aimed to use immunohistochemical staining for retrospective analysis of screening for PA in patients with adrenal surgery in Chinese to improve the screening rate of PA. Design and method: A total of 101 patients who were diagnosed with adrenal tumors and treated with adrenalectomy were collected. Immunohistochemical staining for anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies was performed on postoperative specimens. Analysis of staining results according to the expert consensus on the histopathology of PA. Results: Of the 101 patients included, 25 (24.75%) patients had completed secondary hypertension screening before surgery. Of the remaining 76 (75.25%) patients, immunohistochemical staining was identified in 13 patients (12.87%) with PA and 4 patients (3.96%) with autonomous secretion of cortisol. Only APM or MAPM was seen in 42 patients (41.58%). APM and MAPM were used as a potential diagnostic basis leading to PA, and functional lesions were observed in postoperative pathology in 83.17% of patients. Still, 16.83% of patients did not show clear functional histopathology on pathological staining. The overall incidence of APM and MAPM was 64.36%. Increased prevalence of APM and MAPM in patients older than or equal to 50 years old compared to patients younger than 50 years old (67.14% versus. 58.06%) and in female patients compared to males (77.78% versus. 42.11%). There without a significant difference between different ages (χ2 = 0.772, P = 0.380) but there was a significant difference between genders (χ2 = 13.149, P &lt; 0.001). Conclusions: The screening rate of PA before adrenalectomy was less than 1/4. More than 40% of patients had pathologically confirmed APM or MAPM without systematic PA screening. Meanwhile, 16.83% of patients undergoing adrenal surgery had no clear functional histopathological manifestations. The problem of inadequate screening for PA still exists. Immunohistochemistry by anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies is an important tool in the pathological diagnosis of PA and will help identify potential autonomous secretion of aldosterone and guide improved screening for PA.

Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches.

The majority of incidentally discovered adrenal tumours are benign adrenocortical adenomas and the prevalence of adrenocortical adenomas is around 1-7% on cross-sectional abdominal imaging. These can be non-functioning adrenal tumours or they can be associated with autonomous cortisol secretion on a spectrum that ranges from rare clinically overt adrenal Cushing syndrome to the much more prevalent mild autonomous cortisol secretion (MACS) without signs of Cushing syndrome. MACS is diagnosed (based on an abnormal overnight dexamethasone suppression test) in 20-50% of patients with adrenal adenomas. MACS is associated with cardiovascular morbidity, frailty, fragility fractures, decreased quality of life and increased mortality. Management of MACS should be individualized based on patient characteristics and includes adrenalectomy or conservative follow-up with treatment of associated comorbidities. Identifying patients with MACS who are most likely to benefit from adrenalectomy is challenging, as adrenalectomy results in improvement of cardiovascular morbidity in some, but not all, patients with MACS. Of note, diagnosis and management of patients with bilateral MACS is especially challenging. Current gaps in MACS clinical practice include a lack of specific biomarkers diagnostic of MACS-related health outcomes and a paucity of clinical trials demonstrating the efficacy of adrenalectomy on comorbidities associated with MACS. In addition, little evidence exists to demonstrate the efficacy and safety of long-term medical therapy in patients with MACS.

Subtyping of Cushing's syndrome: a step ahead.

Cushing's Syndrome (CS) is a rare disease due to chronic endogenous cortisol secretion. In the last years, new acquisitions enlarged the spectrum of differential diagnosis, historically divided into ACTH-dependent and ACTH-independent forms. Moreover, the increased awareness of the detrimental cortisol effects on cardiometabolic health and the risk of cardiovascular events lead to increased diagnosis of mild forms, especially in the context of adrenal incidentalomas. We provide and up-to-date narrative review of the most recent literature regarding the challenges of CS diagnosis. After the description of the diagnostic tools available, we describe the characterization of functional non-neoplastic hypercortisolism (formerly known as pseudo-Cushing state), then we report the subtyping of the different conditions of hypercortisolism: the differential diagnosis of ACTH-dependent forms and the management of adrenal hypercortisolism, with peculiar attention to the new genetic classification of adrenal CS, mild autonomous cortisol secretion and bilateral adrenal adenomas.

Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas

ObjectiveTo assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. MethodsThe plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. ResultsSeventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11β-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. ConclusionsWe have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802). Referent subjects included participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) study (n=5241). GlycA, BCAA, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes mellitus and statin therapy. In age-and sex-adjusted comparison to referent subjects, increased GlycA was noted in all patient categories, increased BCAA in NFA, MACS, CS, PA and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of subjects with diabetes and cardiovascular disease. Patients with functioning and non-functioning adrenal masses demonstrated increased GlycA and BCAA, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms

Introduction/ObjectivesMutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. Methods, Results and ConclusionsWe present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms

Introduction/ObjectivesMutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. Methods, Results and ConclusionsWe present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

An Overlooked Disease: Minimal Autonomous Cortisol Secretion (MACS). A Narrative Review.

A far more common disease than Cushing's syndrome is subclinical hypercortisolism or mild autonomous cortisol secretion (MACS), with an overall prevalence of 0.2-2%. This review aims to shed light on the prevalence, screening and diagnostic criteria, comorbidities, and management of Mild Autonomous Cortisol Secretion (MACS). Studies eligible targeted MACS regarding prevalence, screening, comorbidities, management, and clinical outcome. This is a mini-review. IRB approval was not needed. The 1 mg Dexamethasone suppression test (DST) remains the first screening test. MACS is associated with adverse cardiometabolic and renal outcomes, osteoporosis and osteopenia, immunodeficiency, depression, coagulopathy, and sarcopenia. Surgery is the gold standard treatment. Medical therapy is recommended when surgery is contraindicated or not feasible. Clinically silent hypercortisolism is a frequent entity that necessitates early detection and treatment. The production of cortisol should be looked at as a spectrum where subtle, undetectable levels can still be produced. They know its association with adverse health outcomes. MACS is no longer considered an asymptomatic disorder; repeated hormonal and functional tests are crucial to prevent multiorgan damage.

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.

Adrenalectomy Improves Body Weight, Glucose, and Blood Pressure Control in Patients With Mild Autonomous Cortisol Secretion: Results of an Randomized Controlled Trial by the Co-work of Adrenal Research (COAR) Study.

To assess the metabolic effects of adrenalectomy in patients with mild autonomous cortisol secretion (MACS). Despite retrospective studies showing the association of adrenalectomy for MACS with beneficial metabolic effects, there have been only 2 randomized prospective studies with some limitations to date. A prospective, multicenter study randomized 132 patients with adrenal incidentaloma without any features of Cushing syndrome but with serum cortisol >50 nmol/L after a 1 mg overnight dexamethasone suppression test into an adrenalectomy group (n = 66) or control group (n = 66). The primary outcomes were changes in body weight, glucose, and blood pressure (BP). Among the 118 participants who completed the study with a median follow-up duration of 48 months (range: 3-66), the adrenalectomy group (n = 46) exhibited a significantly higher frequency of improved weight control, glucose control, and BP control (32.6%, 45.7%, and 45.7%, respectively) compared with the control group (n = 46; 6.5%, P = 0.002; 15.2%, P = 0.002; and 23.9%, P = 0.029, respectively) after matching for age and sex. Adrenalectomy [odds ratio (OR) = 10.38, 95% CI = 2.09-51.52, P = 0.004], body mass index (OR = 1.39, 95% CI = 1.08-1.79, P = 0.010), and cortisol after a 1 mg overnight dexamethasone suppression test levels (OR = 92.21, 95% CI = 5.30-1604.07, P = 0.002) were identified as independent factors associated with improved weight control. Adrenalectomy (OR = 5.30, 95% CI = 1.63-17.25, P = 0.006) and diabetes (OR = 8.05, 95% CI = 2.34-27.65, P = 0.001) were independently associated with improved glucose control. Adrenalectomy (OR = 2.27, 95% CI = 0.87-5.94, P = 0.095) and hypertension (OR = 10.77, 95% CI = 3.65-31.81, P < 0.001) demonstrated associations with improved BP control. adrenalectomy improved weight, glucose, and BP control in patients with MACS.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients

ObjectiveDue to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DesignA retrospective, observational cohort study. MethodsWe included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. ResultsA total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71–80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. ConclusionPrevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

The value of plasma metanephrine measurements during adrenal vein sampling.

The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS. This is a diagnostic accuracy study in a tertiary referral endocrinology department. Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS. There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet-PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet-AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%). Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy. Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

Bone density in patients with nonfunctional adrenal incidentaloma

Aims: Adrenal incidentalomas (AI) are adrenal masses that are detected incidentally in imaging studies performed for different reasons in people who do not have any complaints suggestive of adrenal gland disease. The overall prevalence, approximately just over 4%, increases with age. AI is detected in approximately 10% of people over the age of 70. In this context, we thought that CT imaging, which is already used in the diagnosis and follow-up of AI, can contribute to the evaluation of muscle and bone mass without creating additional costs. Methods: In this retrospective study, 39 patients who were followed up with NFAI by the endocrinology department and 30 healthy individuals with normal adrenal imaging in the abdominal CT examination as the control group were included. Patients with chronic diseases or drug use that may affect bone and muscle mass, and individuals in the postmenopausal period were excluded in this study. Endocrine tests performed to exclude autonomous cortisol secretion, pheochromocytoma and primary hyperaldosteronism; VMA and fractionated metanephrines in 24-hour urine, cortisol values after 1 mg dexamethasone suppression test, baseline serum dehydroepiandrosterone sulfate (DHEAS) levels and plasma aldosterone (ng/dl)/renin (ng/ml/hour) ratio were measured. Autonomous cortisol production was excluded in patients with serum cortisol below 1.8 mcg/dl after 1 mg dexamethasone suppression. Results: 39 patients with NFAI and 30 healthy volunteers participated in the study. In the NFAI group, 69.2% (n= 27) were female and 30.8% (n=12) were male. In the healthy control group 63.3% (n=19) of the people were female and 37.7% (n=11) were male. There was no statistically significant difference between the two groups in terms of gender (p=061). The mean age of the NFAI group is 43 and the mean age of the control group is 49, and there was no statistically significant difference in age between the two groups (p=0.06) Conclusion: No decrease was found in BMD and paravertebral muscle mass values in the measurements made at L1-3 vertebral level with CT in NAFI patients. Further studies are needed in a larger patient population where the results are evaluated together with the femur and vertebral BMD measurements by DXA method, and muscle strength and performance are evaluated in addition to muscle mass in terms of sarcopenia.