Adrenal Incidentalomas Patients Research Articles

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study

BackgroundThe aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors.MethodsThe clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation.ResultsIn the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma.ConclusionsNeuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

Sedmogodišnje praćenje bolesnika sa adrenalnim incidentalomom - iskustvo jednog centra

Introduction/Aim. Adrenal incidentalomas (AIs) are defined as tumours revealed during imaging procedures of abdomen or abdominal laparotomy, performed in patients without previous suspicion for adrenal disease. This study was conducted to evaluate morphological and functional features of AIs seven years after the initial diagnosis. Patients and methods. Thirty-eight AI patients were monitored for seven years, with CT scans used for morphological follow-up. Hormonal activity assessments included basal cortisol levels, adrenocorticotropic hormone, overnight Dexamethasone suppression test, plasma or urinary metanephrines, vanillymandelic acid, electrolytes, hematocrit, acid-base status, oral glucose tolerance test, and chromogranin A. Results. Functional activity was confirmed in six patients, with mild autonomous cortisol secretion (MACS) detected in two patients. Nine patients underwent adrenalectomy. Histopathological examination revealed hormonal activity in six cases, adrenocortical carcinoma was found in one patient, while secondary deposits from bronchial carcinoma were detected in one patient. Among the remaining 29 patients observed for the first year, tumor size remained stable. After seven years, two patients experienced tumor enlargement ≥ 1 cm, along with the development of MACS on endocrine evaluation. Adrenalectomy was recommended for one patient due to tumor size exceeding 4 cm. Conclusion. The initial adrenal incidentaloma (AI) evaluation must include comprehensive diagnostic procedures for surgical consideration. Subsequent follow-up should include CT imaging after 12 months to monitor the tumor growth. Although mild autonomous cortisol secretion does not tend to progress to overt Cushing's syndrome, it can develop in patients initially considered to have hormonally inactive tumor. Our findings suggest that even small adrenal masses (< 4 cm) can enlarge over seven years, potentially evolving into MACS. Therefore, regular long-term monitoring every 5 - 7 years is recommended.

Sedmogodišnje praćenje bolesnika sa adrenalnim incidentalomom - iskustvo jednog centra

Introduction/Aim. Adrenal incidentalomas (AIs) are defined as tumours revealed during imaging procedures of abdomen or abdominal laparotomy, performed in patients without previous suspicion for adrenal disease. This study was conducted to evaluate morphological and functional features of AIs seven years after the initial diagnosis. Patients and methods. Thirty-eight AI patients were monitored for seven years, with CT scans used for morphological follow-up. Hormonal activity assessments included basal cortisol levels, adrenocorticotropic hormone, overnight Dexamethasone suppression test, plasma or urinary metanephrines, vanillymandelic acid, electrolytes, hematocrit, acid-base status, oral glucose tolerance test, and chromogranin A. Results. Functional activity was confirmed in six patients, with mild autonomous cortisol secretion (MACS) detected in two patients. Nine patients underwent adrenalectomy. Histopathological examination revealed hormonal activity in six cases, adrenocortical carcinoma was found in one patient, while secondary deposits from bronchial carcinoma were detected in one patient. Among the remaining 29 patients observed for the first year, tumor size remained stable. After seven years, two patients experienced tumor enlargement ≥ 1 cm, along with the development of MACS on endocrine evaluation. Adrenalectomy was recommended for one patient due to tumor size exceeding 4 cm. Conclusion. The initial adrenal incidentaloma (AI) evaluation must include comprehensive diagnostic procedures for surgical consideration. Subsequent follow-up should include CT imaging after 12 months to monitor the tumor growth. Although mild autonomous cortisol secretion does not tend to progress to overt Cushing's syndrome, it can develop in patients initially considered to have hormonally inactive tumor. Our findings suggest that even small adrenal masses (< 4 cm) can enlarge over seven years, potentially evolving into MACS. Therefore, regular long-term monitoring every 5 - 7 years is recommended.

Hair cortisol and endocannabinoid measurement in patients with adrenal incidentalomas: a case-control study.

The role of endocannabinoids (ECs) in the regulation of the hypothalamic-pituitary-adrenocortical axis has already been studied; however, data are scarce in humans. The aim of our study was to analyze EC [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and cortisol (F) levels in hair samples of patients with adrenal incidentalomas (AIs) in comparison with those found in controls and assess their association with the hormone profile. Forty-four patients with AIs [32 with non-functioning AIs (NFAIs) and 12 with possible autonomous secretion (PACS)] and 44 controls were recruited. Basal and post-1mg overnight dexamethasone suppression test (ODST) F, adrenocorticotropic hormone, dehydroepiandrosterone sulfate, and 24-h urinary free cortisol were analyzed. After hair collection, EC and F levels were measured by liquid chromatography tandem-mass spectrometry. There was no difference between the groups regarding age, sex, and metabolic status. Significantly decreased hair AEA and 2-AG levels were found in patients with AIs compared to controls (p < 0.001 and p = 0.002, respectively) as well as between NFAI or PACS and controls (p < 0.001 or p = 0.002 and p = 0.038 or p = 0.02, respectively). Among the AI patients, EC levels tended to be lower in the PACS group. AEA hair levels were negatively correlated with F levels post-1mg ODST (rs = -0.257, p = 0.033). We found no significant difference comparing hair F between the groups. Our findings suggest that hair EC measurement could be a potential biomarker in the evaluation of patients with AIs, whereas hair F analysis is not a useful diagnostic test for mild hypercortisolemia.

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.

The utility of salivary cortisone in the overnight dexamethasone suppression test in adrenal incidentalomas.

Guidelines recommend the assessment of cortisol secretion in patients with adrenal incidentalomas (AI) using the overnight dexamethasone suppression test (ONDST). This requires attendance to a health care facility and venepuncture. Alternatively, the ONDST can be done by measuring salivary cortisol and cortisone which can be collected at home. We aimed to assess the utility of these measurements in patients with AI. A retrospective analysis of data from 173 patients with AI who underwent an ONDST and salivary cortisol/cortisone diurnal studies. Serum and salivary cortisol and salivary cortisone were collected at 09:00, late night and at 09:00 post dexamethasone. Dexamethasone levels were measured in the post dexamethasone samples. Serum and salivary samples were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Stata. We identified a strong correlation between salivary cortisone and serum cortisol post 1 mg dexamethasone (r = 0.95). Stepwise multivariate regression showed that post-dexamethasone salivary cortisone, baseline serum cortisol, salivary cortisone suppression (pre: post-dexamethasone ratio) and sex as the only significant or near significant independent variables. Performance of predictive indices using these four parameters (sensitivity = 88.5%, specificity = 91.2%; kappa 0.80) and post-dexamethasone salivary cortisone alone (sensitivity = 85.3%, specificity = 91.7%; kappa 0.77) were comparable when used to predict an ONDST serum cortisol of ≤50 nmol/L.No correlation was observed with any of the other measured parameters. In AI patients, post dexamethasone, salivary cortisone correlates very strongly with serum cortisol in the ONDST and could therefore be used as an alternative sampling method which does not require venepuncture or attendance to hospital.

Hypertension Resolution after Laparoscopic Adrenal Tumor Resection in Patients of Adrenal Incidentaloma with Normal Hormone Levels

Introduction: Postoperative hypertension resolution among patients with adrenal incidentalomas and normal hormone levels was unknown. Identifying the predictive factors was beneficial to the management of adrenal incidentalomas. Methods: We conducted a retrospective cohort study, recruiting patients undergoing laparoscopic adrenal tumor resection for adrenal incidentaloma with hypertension and normal hormone levels. Demographic, clinical, treatment, and laboratory data were collected and compared. We used univariable and multivariable logistic regression methods to identify the predictive factors of postoperative hypertension resolution. Results: Of the 171 patients in our study, 130 (76.0%) patients performed a resolution of hypertension, and 57 (33.3%) patients had a significant reduction. Multivariate logistic regression analysis showed that the male sex (odds ratio (OR) 0.305, 95% confidence interval (CI): 0.098–0.948, p = 0.040), body mass index (BMI) (OR 0.973, 95% CI: 0.670–0.938, p = 0.007), aldosterone and plasma renin activity ratio (APR) in erect position (OR 1.206, 95% CI: 1.042–1.397, p = 0.012), and preoperative systolic pressure (OR 1.044, 95% CI: 1.009–1.080, p = 0.014), were significantly associated with the outcomes of hypertension resolution. Discussion/Conclusion: Adrenal incidentalomas patients with hypertension and normal hormone levels would perform hypertension resolution after laparoscopic adrenal tumor resection, especially for females with low BMI, high preoperative systolic blood pressure, and high APR (erect position).

Is there a role for the IGF system and epidermal growth factor (EGF) in the pathogenesis of adrenocortical adenomas? A preliminary case-control study.

Adrenal incidentalomas (AI) are very common and mostly they are non-functioning adenomas (NFA). NFAs are often associated with insulin resistance and metabolic syndrome. Several biomarkers, including certain growth factors, may participatein the pathogenesis ofmetabolic changes in patients with adrenal adenomas.Patients with NFA and age-matched control subjects were enrolled in the study. Data on age, gender, presence of metabolic syndrome or its components were obtained for each subject. Blood samples were obtained and glycemia, insulinemia, lipid profile, and selected growth factor levels were measured. Forty-three patients with NFA and 40 controls were included in the study. Differences were not found in the metabolic syndrome and its components prevalence or in the biochemical profile between patients and the control group. Significant differences were noticed in the levels of IGF1, IGF2, and IGFBP3 (p=0.016, p=0.005, p=0.004, respectively), but there were no differences in VEGF or EGF concentrations. In NFA patients, an association between glycemia and EGF levels was present (p=0.026). No significant correlations between tumor size and insulin or growth factor concentrations were present in AI patients. Significantly higher serum IGF1, IGF2, and IGFBP3 concentrations in NFA patients may support the role of the IGF axis in the pathogenesis of adrenocortical lesions.No correlation between IGFs or IGFBP3 and parameters of glucose or lipid metabolism was found. Present results may support the role of the growth hormone axis rather than hyperinsulinemia and insulin resistance in the pathogenesis of adrenocortical adenomas.

Defining Nonfunctioning Adrenal Adenomas on the Basis of the Occurrence of Hypocortisolism after Adrenalectomy.

BackgroundIn patients with adrenal incidentalomas (AIs), there is uncertainty on how to rule out hypercortisolism. The occurrence of postsurgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of presurgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after the 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC), and adrenocorticotropin (ACTH) to predict the absence of PSH in AI patients undergoing surgery.MethodsIn 60 patients who underwent AI excision, cortisol secretion was assessed by a low-dose corticotropin stimulation test or insulin tolerance test when needed. We searched for the lowest presurgical value of F-1mgDST, UFC, and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion.ResultsThe lowest values of F-1mgDST, UFC, and MSC and the highest value for ACTH in PSH patients were 1.2 µg/dL (33 nmol/L), 10.4 µg/24 hours (29 nmol/24 hours), 1.2 µg/dL (33 nmol/L), and 26.9 pg/mL (6 pmol/L), respectively, but only F-1mgDST <1.2 µg/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST <1.2 µg/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome, and these subjects tended to have a better metabolic profile than those with F-1mgDST ≥1.2 µg/dL (33 nmol/L)ConclusionIn AI patients a F-1mgDST <1.2 µg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients.

Cardiovascular and metabolic risk factors in patients with subclinical Cushing.

Adrenal incidentalomas (AI) are discovered after work-up unrelated to adrenal gland diseases; up to 30% of AI show subclinical endogenous cortisol excess (SH), frequently associated to hypertension, obesity, metabolic disorders and increased incidence of cardiovascular events (CVEs). We analysed 628 AI patients divided into two groups: 471 non-functional adrenal adenoma (NFA) and 157 SH. All patients underwent complete examinations, 24-h ambulatory blood pressure monitoring, biohumoral parameters and vascular damage markers, such as c-IMT and ankle brachial index. After long-term follow-up, we registered newly onset of CVEs such as myocardial infarction (MI), percutaneous stenting and surgical bypass (PTA/CABG), stroke, overall/cardiovascular mortality. Moreover, SH patients underwent to surgical (SSH) or pharmacological treatment (MSH). SH patients showed higher prevalence of metabolic syndrome, diabetes mellitus, and previous CVEs respect NFA at baseline. After follow-up MSH group showed higher recurrence of major CV events compared with NFA and SSH (RR 2.27 MSH vs NFA for MI; RR 2.30 MSH vs NFA for PTA/CABG; RR 2.41 MSH vs NFA for stroke). In SSH there was a significant reduction of the number of antihypertensive medications needed to reach target blood pressure levels (2.3 ± 1.0 to 1.5 ± 0.4 drugs). None differences were found in SH patients, distinguished in relation to cortisol plasma levels after dexamethasone suppression test (1.8-5 µg/dL, above 5 µg/dL). SH is linked to relevant cardiovascular and metabolic alterations, leading to worsen clinical outcomes. In eligible patients, adrenalectomy is valid and safe option to treat SH, reducing cardiometabolic abnormalities.

Three-year follow up of adrenal incidentalomas in a New Zealand centre.

The international guidelines for management of adrenal incidentalomas (AI) are becoming more conservative. These changes are based on the growing body of evidence suggesting that non-functioning adenomas have a low likelihood of becoming functional or malignant over time. To follow up at least 100 patients for 3 years who were originally found to have benign adrenal adenomas which were non-functional or had subclinical Cushing syndrome (SCS). This study prospectively evaluated consecutive patients aged 18 years or older with benign adrenal incidentalomas (AI), not treated with adrenalectomy, which were non-functioning or had SCS. The initial and follow-up evaluation, including clinical assessment, hormonal investigations and imaging were coordinated via a standardised nurse-led AI clinic. Of 233 patients referred to the AI clinic, 101 patients met the inclusion criteria and completed 3-year follow up. Most of those excluded were due to incomplete initial or follow-up evaluation or were not true AI. Most AI either remained stable or decreased in size on repeat imaging, while 5% of patients had AI enlargement of >5 mm diameter. No patient developed features suggesting adrenal carcinoma. Ninety-two patients had an initial diagnosis of non-functioning adenoma and nine patients had SCS. After 3 years (range 2.9-4.7 years), five of the nine patients with SCS showed normalisation of cortisol parameters (44%), and five of the 92 non-functional AI patients developed SCS (5%). After 3 years of follow up, approximately half of patients with SCS normalised, while 5% of patients with initially non-functioning adenomas developed biochemical evidence of SCS. This study found a low likelihood of progressive hormonal excess with no evidence of malignancy developing on follow-up evaluation, providing support for the shift towards the more conservative approach to management of AI recommended in recent guidelines.

SAT-365 Prevalence and Clinical Features of Adrenal Incidentalomas: A Prospective Study in an Unselected Population

Context. The widespread use of cross-sectional imaging in medical practice has increased detection of adrenal tumors, which are most frequently unexpected prior to their discovery (adrenal incidentalomas). Most adrenal incidentalomas (AI) are benign and frequently cause low-grade cortisol excess that may portend adverse clinical consequences. However, this association is subject to confounding by indication since more diagnostic tests are done in diseased patients. Objective. To assess prospectively the prevalence of AI in an unselected adult population performing abdominal CT in our catchment area, and to evaluate the demographic, laboratory and clinical features of AI patients. Design and setting. Monocentric, prospective study. Patients. A consecutive series of 601 unselected patients undergoing abdominal CT as part of their management. Patients with any known adrenal disorder or malignancy were excluded. Results. Of the 601 patients, aged 63.5 ± 14.4 years, 55.4% had hypertension, 15.1% diabetes, 16.8% dyslipidemia and 16% previous CV events. These characteristics are overall comparable to the background general population. We found serendipitously 44 adrenal tumors (7.3%), 43 with radiological features of benign cortical adenoma (density <10 HU) and 1 with indeterminate features, which was a pheochromocytoma. Mass size ranged between 1-5 cm (median 2 cm) and tumors were bilateral in 29.5%. Patients with AI compared to patients without were more frequently suffering from diabetes (31.8% vs 14.2%; p=0.004), showing higher BMI (27.6 ± 6.2 vs. 25.6 ± 4.8; p=0.009) and larger waist (101.2 ± 13.9 cm vs. 95.3 ± 13.9 cm; p=0.007). No differences were found in frequency of hypertension, dyslipidemia or history of CV events. Forty patients underwent a 1-mg overnight dexamethasone test (DST) and 20 (50%) did not suppress cortisol below 1.8 μg/dL (4 had post-DST cortisol >5.0 μg/dL). Post-DST cortisol levels were not different between diabetic and non-diabetic AI patients (3.5 ± 4.0 µg/dL vs. 2.4 ± 2.5 µg/dL). In multivariate analysis, diabetes was significantly associated with AI (p=0.003). Conclusions. We confirm in a prospective study the high prevalence of previously unsuspected adrenal tumors, most of which are benign adenomas. Moreover, we found a significant association between adrenal incidentalomas and diabetes. Since our patients were recruited at the radiology department, this finding is not confounded by selection bias.

Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship?

A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)-dependent adrenal pathologies are well documented in patients with LH-responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis. The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1mg overnight dexamethasone test (1mg DST); and ATS and 1mg DST cortisol in AI patients. This was a case-control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age-, BMI-, LH- and menopause duration-matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA-IR). Luteinizing hormone and ATS are in a significant positive correlation with HOMA-IR and 1mg DST cortisol in menopausal patients with AI and (P)ACS. Our data point to a possible cause-effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.

Surgery versus conservative management for subclinical Cushing's syndrome in adrenal incidentalomas

Objective: To determine the effect of the surgical and conservative approaches on the metabolic profiles in patients with subclinical Cushing's syndrome (SCS) in adrenal incidentalomas (AI). Methods: A hundred and thirty AI patients with SCS in Department of Endocrinology, PLA General Hospital between January 2008 and December 2016 were studied, surgery was performed in 88 patients (surgical group), and the rest received conservative approach (conservative group). The improvement/worsening of blood pressure, blood glucose, lipid profiles and body weight after a duration of >18 months follow-up were analyzed, respectively. Results: Baseline demographics, clinical characteristics were similar between surgical and conservative groups. In the surgical group, blood pressure, blood glucose, lipid profiles and body weight improved more frequently than that in conservative group (29.69% vs 3.12%, P=0.003; 10.94% vs 3.12%, P=0.262; 7.81% vs 3.12%, P=0.660; 39.06% vs 9.38%, P=0.004, respectively). In conservative group, blood pressure, blood glucose, lipid profiles and body weight worsened more frequently than that in surgical group (28.13% vs 0, P<0.001; 25.0% vs 0, P<0.001; 18.75% vs 0, P=0.003; 40.62% vs 20.31%, P=0.051, respectively). Logistic regression analysis indicated surgical treatment was associated with improvement of blood pressure (OR=10.687, 95%CI: 1.279-89.299) and weight loss (OR=5.541, 95%CI: 1.404-21.872) independently of gender, age, duration of follow-up, serum cortisol level after 1 mg-dexamethasone suppression test and the mass size. Conclusion: In AI patients with SCS, surgery was beneficial in the aspect of metabolic profiles.

Comparison of echocardiographic findings in patients with nonfunctioning adrenal incidentalomas

Adrenal incidentalomas (AIs) are usually discovered incidentally after imaging unrelated to adrenal glands. We aimed to evaluate standard risk factors for systemic atherosclerosis and echocardiographic changes in patients with nonfunctioning AIs and compare them with normal subjects. We evaluated 70 patients diagnosed with AIs and 51 healthy controls. Mean levels were determined for HbA1c, LDL, uric acid, fasting plasma insulin, HOMA, and neutrophil-to-lymphocyte ratio (NLR), and these values were found to be significantly higher in the patients than the controls. The mean left atrial diameter, interventricular septum thickness, posterior wall thickness, left ventricular mass, E-wave deceleration time, isovolumetric relaxation time, and the median ratio of the early transmittal flow velocity to the early diastolic tissue velocity (E/Em) were higher in patients with AIs compared to controls. The mitral annular early diastolic velocity was lower in patients with AIs. The mean aortic diastolic diameter, stiffness index (SI), and aortic strain were higher, and aortic distensibility was lower in the patients. The mean right ventricular diameter, right atrial major-axis diameter, and right atrial minor-axis diameter were statistically higher in the patient group than the controls. A negative correlation was found between the NLR and aortic strain and aortic distensibility, while a positive correction was found between the NLR and SI. We found altered left ventricular (LV) and right ventricular (RV) echocardiographic findings in patients with AIs without known cardiovascular disease. Aortic stiffness was also increased. These changes may be related to an increase in cardiovascular risk factors in AI patients.

Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. Prospective study in a tertiary hospital. Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54±1·7years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1±0·8 to 2·3±0·8cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency Presenting as Adrenal Incidentaloma: A Systematic Review and Meta-Analysis

Adrenal incidentalomas (AIs) may be due to congenital adrenal hyperplasia (CAH) due to homozygous CYP21A2 mutations, or perhaps from heterozygous carrier status. It is unclear if genetic or biochemical testing of CYP21A2 status in AI is justified, despite its potential for avoiding adrenal crises in those referred for adrenalectomy. We systematically searched PubMed/MEDLINE for articles published up to October 19, 2015 containing all terms associated with adrenal tumors and CAH. Meta-analyses were used to estimate the CAH or carrier prevalence in AI and assess clinical factors that may guide testing. Thirty-six publications were included. Of AI patients biochemically screened for CAH, 58/990 (5.9%) were diagnosed with CAH. Genetic screening of all AIs revealed only 2/252 (0.8%) with clear CAH. The carrier prevalence was 10.2% (36/352). The rate of 0.8% (8/1,000) genetically confirmed CAH is higher than the 1/15,000 affected by classic CAH or 1/1,000 by nonclassic CAH in the Caucasian population. The rate of heterozygous CYP21A2 mutation frequency is similar to those in reported in population studies. Levels of both basal and stimulated 17-hydroxyprogesterone positively correlated with AI diameter. Although bilateral incidentalomata were frequent in CAH, their presence did not predict CYP21A2 status. The presence of an AI does not increase the probability of detection of CAH or CYP21A2 carrier status to the extent routine genetic testing is justified. Screening with 17-hydroxyprogesterone levels appears to lack specificity in the setting of an AI. CYP21A2 mutation analysis is probably the only reliable method for CAH diagnosis in AIs. ACC = adrenocortical carcinoma ACTH = adrenocorticotropic hormone AI = adrenal incidentaloma CAH = congenital adrenal hyperplasia NCAH = nonclassic congenital adrenal hyperplasia 17OHP = 17-hydroxyprogesterone SV = simple virilizing.

Prediction of Vertebral Fractures in Patients With Monolateral Adrenal Incidentalomas.

Subtle hypercortisolism is associated with an increased risk of vertebral fracture (VFx). The objective was to determine the best parameters of cortisol secretion for detecting the VFx risk in patients with adrenal incidentalomas (AI). This was a retrospective (cross-sectional arm) and prospective (longitudinal arm) design. In the cross-sectional arm, we assessed the accuracy of the cortisol secretion indexes in identifying the patients with VFx (prevalent VFx). In the longitudinal arm, we tested the cortisol secretion parameters, which were able to identify the prevalent VFx, for the prediction of the occurrence of a new VFx (incident VFx) in AI patients followed-up for at least 2 years. Four referral Italian endocrinology units participated in this study. A total of 444 and 126 AI patients without symptoms of hypercortisolism enrolled in the cross-sectional arm and longitudinal arm, respectively. Serum cortisol after a 1-mg dexamethasone suppression test (1 mg DST), urinary free cortisol, ACTH, bone mineral density at lumbar spine and femoral neck (by dual-energy x-ray absorptiometry), and the VFx presence (by x-ray). The cortisol levels after 1 mg DST that were greater than 2.0 μg/dl (55 nmol/liter) were the best criteria for detecting patients with both prevalent (73.6% sensitivity, 70.5% specificity) and incident VFx (80% sensitivity, 68.8% specificity) and were associated with a 10-fold increased risk of a new VFx (odds ratio,10.27; 95% confidence interval, 3.39-31.12; P < .0001), regardless of age, gender, bone mineral density at lumbar spine, and prevalent VFx. In AI patients without symptoms of overt hypercortisolism, the cortisol levels after 1 mg DST greater than 2.0 μg/dl (55 nmol/liter) represent the best criterion for detecting prevalent and incident VFx.

Abnormal Responsiveness to Dexamethasone-Suppressed CRH Test in Patients With Bilateral Adrenal Incidentalomas.

The bilateral formation of nodules indicates that the pathogenesis of bilateral adrenal incidentalomas (AI) may differ from that of unilateral AI. A possible role of hypothalamo-pituitary-adrenal (HPA) axis dysregulation in their formation has not been investigated. The objective of the study was to evaluate the presence of altered feedback regulation of HPA axis in patients with bilateral AI. The dexamethasone (DEX) suppression-CRH test was used to assess ACTH and cortisol responses in controls and patients with unilateral and bilateral AI. The study was conducted at endocrine departments of two tertiary centers. We studied 24 controls and 39 patients with unilateral and 46 with bilateral AI. All subjects underwent standard low-dose dexamethasone suppression followed by iv bolus administration of human CRH (100 μg). Bilateral AI had higher levels of ACTH and cortisol after the DEX-CRH challenge compared with both controls (P < .01 for ACTH and P < .001 for cortisol) and unilateral AI (P < .01 for ACTH and cortisol). A positive response, defined as peak ACTH greater than 10 pg/mL at 15 and/or 30 minutes followed by a significant rise in cortisol levels, was noted in 41.3% of bilateral vs 2.6% in unilateral AI (P < .001). Bilateral responders did not differ from nonresponders in demographic or hormonal characteristics, but they had larger total adrenal size compared with nonresponders. A significant proportion of patients with bilateral AI demonstrate positive responses to the DEX-CRH test compared with unilateral AI, providing ground for potential involvement of HPA axis dysregulation in the pathogenesis, in at least a subgroup, of bilateral AI patients.

Long-Term Follow-Up in Adrenal Incidentalomas: An Italian Multicenter Study

The long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AIs) are unknown. In this retrospective multicentric study, 206 AI patients with a ≥5-year follow-up (median, 72.3 mo; range, 60-186 mo) were enrolled. Adrenocortical function, adenoma size, metabolic changes, and incident cardiovascular events (CVEs) were assessed. We diagnosed SH in 11.6% of patients in the presence of cortisol after a 1 mg-dexamethasone suppression test >5 μg/dL (138 nmol/L) or at least two of the following: low ACTH, increased urinary free cortisol, and 1 mg-dexamethasone suppression test >3 μg/dL (83 nmol/L). At baseline, age and the prevalence of CVEs and type 2 diabetes mellitus were higher in patients with SH than in patients without SH (62.2 ± 11 y vs 58.5 ± 10 y; 20.5 vs 6%; and 33.3 vs 16.8%, respectively; P < .05). SH and type 2 diabetes mellitus were associated with prevalent CVEs (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0; and OR, 2.0; 95% CI, 1.2-3.3, respectively), regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients who were without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (sensitivity, 73.3%; specificity, 60.5%; P = .014). Weight, glycemic, lipidic, and blood pressure control worsened in 26, 25, 13, and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of at least two metabolic parameters (OR, 3.32; 95% CI, 1.6-6.9) and with incident CVEs (OR, 2.7; 95% CI, 1.0-7.1), regardless of age and follow-up. SH is associated with the risk of incident CVEs. Besides the clinical follow-up, in patients with an AI >2.4 cm, a long-term biochemical follow-up is also required because of the risk of SH development.