Adrenal Adenoma Research Articles

Adrenal Oncocytoma: A Rare Tumor with Conflicting Imaging Features.

Oncocytic adenomas are rare benign tumors that typically originate in organs such as the kidneys, thyroid, parathyroid, salivary glands, or pituitary gland. Oncocytic adenoma of the adrenal gland is extremely rare. It often shows heterogeneous, nonspecific features on anatomic imaging, as well as high 18F-FDG avidity despite its benign nature. The definitive diagnosis relies on histopathologic examination, including immunohistochemistry. We present an incidentally detected benign adrenal oncocytic adenoma with intense 18F-FDG uptake mimicking sinister pathologies.

Development and validation of a model predicting adrenal lipid-poor adenoma based on the minimum attenuation value from non-contrast CT: a dual-center retrospective study

ObjectiveThe early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas.Materials and methodsRetrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models.ResultsThe training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p < 0.05 for all). The AUC for the minAV and CTh models were 0.912 (95% confidence interval [CI]: 0.866–0.957) and 0.916 (95% CI: 0.873–0.958), respectively. Both models exhibited good calibration, with Brier scores of 0.141 and 0.136. In the validation set, the AUCs were 0.871 (95% CI: 0.792–0.951) and 0.878 (95% CI: 0.794–0.962), with Brier scores of 0.156 and 0.165, respectively. The Delong test revealed no statistically significant differences in AUC between the models (p > 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution.ConclusionThe XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.

Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.

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

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

The value of dehydroepiandrosterone sulfate in the differential diagnosis of primary bilateral adrenal macronodular hyperplasia

Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing's disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P<0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L,n=18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n=15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group(P<0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.

Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.

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

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

Prognostic value of fibrinogen change value in adrenocortical carcinoma patients

PurposeThe aim was to explore the preoperative and postoperative fibrinogen changes value (FCV) as a prognosis biomarker for in patients with adrenocortical carcinoma (ACC).MethodsWe identified 42 patients with ACC and 190 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2023. Preoperative fibrinogen, postoperative fibrinogen and follow-up information of the patients were recorded and analysed. The relationship between FCV and overall survival (OS)/ relapse-free survival (RFS) was evaluated.ResultsThe mean level of preoperative and postoperative fibrinogen for ACC were 4.00 ± 1.64 g/L and 2.75 ± 0.59 g/L, respectively (p < 0.001). The mean level of preoperative and postoperative fibrinogen for AA were 2.79 ± 0.59 g/L and 2.71 ± 0.58 g/L, respectively (p = 0.144). In ACC, the lower FCV (≤ 1.25 g/L) showed a significantly poorer RFS than the higher (> 1.25 g/L) (p = 0.007); however, the lower FCV (≤ 1.25 g/L) showed no poorer OS than the higher (> 1.25 g/L) (p = 0.243). On multivariate survival analyses, FCV remained a predictor of RFS (HR 3.138).ConclusionAccording to the data in this study, it can be said that FCV is correlated with prognosis of ACC. The FCV might be a new biomarker for predicting the RFS of ACC.

Before Low Serum Cortisol Can Be Attributed to SARS-Cov-2 Infection, Alternative Causes Must Be Ruled Out

We read with interest Banu et al.,’s article about a cross-sectional study of adrenal function using blood levels of cortisol and adrenocorticotropic hormone (ACTH) in 91 patients with acute SARS-CoV-2 infection. It was found that 27% of patients with severe COVID-19, 26% with mild COVID-19 and 4% with moderate COVID-19 had adrenal insufficiency. Decreased cortisol reserve was found in 6.6% of all patients. It was concluded that the adrenocortical response was impaired in a significant number of non-critically ill COVID-19 patients, with the percentage being highest in patients with severe COVID-19 disease.1 The study is impressive, but some points should be discussed. The major limitation of the study is that imaging of the pituitary gland and hypothalamus was not performed. To rule out pituitary adenoma, hypophysitis, pituitary apoplexy, pituitary abscess, sellar tuberculoma, or hypothalamic stroke or bleeding, magnetic resonance imaging (MRI) of the pituitary gland and the hypothalamus with contrast agent must be performed. Like any other infection, SARS-CoV-2 infection can trigger the appearance of symptoms of a pituitary pathology.2 A second limitation is that imaging of the suprarenal glands was not performed. To assess whether there was adrenal atrophy, adenoma, ischemia, bleeding, or carcinoma, adrenal imaging is mandatory. 3 A third limitation is that current medication was not reported. Several medications are known to affect serum cortisol levels, making it imperative to know all medications regularly taken by the included patients. Ketoconazole, isilodrostat, vitamin D and omega-3 fatty acids in particular are known to be able to reduce cortisol levels in the blood.4 A fourth limitation is that no ACTH stimulation test was performed to determine whether primary or secondary suprarenal insufficiency was present. Determining cortisol levels alone without ACTH stimulation testing is not reliable with regard to cortical adrenal function. A fifth limitation is that serum dehydroepiandrosterone (DHEA) levels were not measured. Since DHEA is the antagonist of cortisol and decreases with age, it is conceivable that high levels of DHEA promoted the reduction of serum cortisol.5 Since low thyroxine levels may be associated with low cortisol levels,6 it would also be desirable to know whether thyroid function was normal or abnormal in the included patients. In summary, the excellent study has limitations that should be addressed before drawing final conclusions. Clarifying the weaknesses would strengthen the conclusions and could improve the study. Serum cortisol levels may be low not only due to SARS-CoV-2 infection but also due to several other causes. Before adrenal insufficiency can be attributed solely to inadequate cortical cortisol production, the entire hypothalamic-pituitary-adrenal axis must be thoroughly examined.

Impact of different peak tube voltage settings on adrenal adenomas attenuation at unenhanced CT.

To assess the influence of peak tube voltage peak setting on adrenal adenomas (AA) attenuation on unenhanced abdominal CT. IRB-approved retrospective observational cohort study. We included 89 patients with imaging-defined AAs with shortest diameter > 6 mm who underwent two or more unenhanced abdominal CTs using at least two different peak tube voltage settings. Two readers independently measured adenoma attenuation on different CT acquisitions by drawing a round ROI on 3 mm thick axial MPR reconstructions encompassing at least 2/3 of the lesion's surface. The mean of the values measured by the two readers was used for further analysis. Interobserver variability was assessed (Intraclass Correlation Coefficient). Attenuation values measured on 100, 110 and 140 kVp acquisitions were compared with standard 120 kVp ones (Bland-Altman analysis). We included 275 unenhanced abdominal CTs (3.1 ± 0.9/patient) in image analysis; 131 acquired at 120 kVp, 65 at 100 kVp, 59 at 110 kVp, and 20 at 140 kVp. 107 lesions were detected in 89 patients (1-4/patient), with a mean maximum diameter of 17 ± 6 mm. Interobserver agreement in attenuation measurement was excellent (ICC: 0.95, CI (92-97)). Median adenoma attenuation was significantly lower on 100 kVp images than on 120 kVp ones (-1 HU, IQR (-5 to 3.6), vs, 2.5 HU, IQR (-1.5 to 8.5); p < 0.001) whereas we didn't find statistically significant differences in adenoma attenuation between 110 kVp or 140 kVp and 120 kVp ones. AA attenuation is significantly lower on unenhanced CT scans acquired at 100 kVp than on those acquired at "standard" 120 kVp. AA attenuation is significantly lower at 100 kVp in comparison to 120 kVp. This might be exploited to increase unenhanced CT sensitivity in adenoma characterisation, but further studies including non-adenoma lesions are mandatory to confirm this hypothesis. CT scans are often acquired using peak tube voltage settings different from the "standard" 120 kVp. AA attenuation varies if CT scans are acquired using different tube peak voltage settings. At 100 kVp AAs show a significantly lower attenuation than at 120 kVp.

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing's Syndrome.

Food-dependent Cushing's syndrome (FDCS) is a rare presentation of hypercortisolism from adrenal origin, mostly observed in primary bilateral macronodular adrenal hyperplasia (PBMAH) but also in some cases of unilateral adrenocortical adenoma. FDCS is mediated by the aberrant expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in adrenocortical cells. GIP, secreted by duodenal K cells after food intake, binds to its ectopic adrenal receptor, and stimulates cortisol synthesis following meals. FDCS was first described more than 35 years ago, and its genetic cause in PBMAH has been recently elucidated: KDM1A inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the KDM1A locus. This causes biallelic inactivation of KDM1A, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the KDM1A genetic screening to all PBMAH patients with signs of FDCS (low fasting cortisol that increases after a mixed meal or oral glucose load) and to all first-degree relatives of KDM1A variant carriers. Given that KDM1A is a tumor suppressor gene that has also been associated with monoclonal gammopathy of uncertain significance and multiple myeloma, the investigation of FDCS in the diagnostic management of patients with PBMAH and further genetic testing and screening for malignancies should be encouraged.

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

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

Pregnancies complicated with functioning adrenal adenomas causing severe obstetric outcomes: a 20-year experience at a tertiary center

BackgroundFunctioning adrenal adenoma during pregnancy is rare, and the diagnosis is challenging owing to unspecific symptoms and restricted investigations. The obstetric outcomes of patients who undergo surgery during pregnancy or who receive only medical treatment are poorly described.ObjectiveThe aim was to investigate the associations between functioning adrenal adenomas and obstetric outcomes.MethodsA retrospective study was performed in a tertiary center over 20 years. The clinical characteristics, management and obstetric outcomes of the diagnosed pregnant women were reviewed.ResultsA total of 12 women were diagnosed with functioning adrenal adenomas during pregnancy from January 2002 to September 2022. Eight women had cortisol-secreting adrenal adenomas, two had excessive catecholamine secretion, and two had primary aldosteronism. The initial symptoms of adrenal adenoma during pregnancy included hypertension or preeclampsia, gestational diabetes mellitus or prepregnancy diabetes mellitus, hypokalemia and ecchymosis. Four women underwent adrenalectomy during pregnancy, while 8 women received only medical therapy. Preterm birth occurred in all patients who received medicine, whereas 1 patient who underwent surgery experienced preterm birth. Among the 8 women in the medical treatment group, 3 had neonates who died.ConclusionsOnce hypertension, hyperglycemia and hypokalemia occur during the 1st or 2nd trimester, pregnant women with adrenal adenomas should be evaluated via laboratory and imaging examinations. The maternal and fetal outcomes were unpredictable owing to the severity of adrenal adenoma, particularly in patients who received only medical treatment. Adrenalectomy should be recommended during pregnancy.

Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review

BackgroundSomatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy.Case presentationA patient with primary aldosteronism (PA) associated with severe Cushing’s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings.ConclusionSomatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

From Adenoma to Carcinoma: the Unexpected Evolution of an Apparently Stable Adrenal Lesion.

There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma. The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease. Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern.

Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and bothmalignancy and steroid secretion patterns. All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1mg-dexamethasone suppression test (1mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1mg-DST cortisol levels and age, but not with tumour size. ConsideringtheACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

Improving adrenalectomies: Safe outcomes of partial adrenalectomies and suitable characteristics

BackgroundPartial adrenalectomy (PA) is increasingly used to treat benign tumors to lower the probability of adrenal insufficiency and reduce need for lifetime hormone replacement therapy. Currently, two major concerns are increased bleeding and non-functioning adrenal remnants. This paper examines these concerns and compares surgical approaches with novel findings. MethodsBetween 1993 and 2023, 72 patients underwent PA for primary adrenal disorders. Demographic, clinicopathologic and outcome data were analyzed for summary statistics, confidence intervals, and heteroscedastic t-test statistics. ResultsThe patients were 17–76 years-old and were 59.7 % female. The PA was on the left 54.2 % and bilaterally 4.2 %. The indications were adrenal adenoma, pheochromocytoma, cyst, hyperplasia, and other. The mean tumor diameter was 2.7 cm (range 0.7-10 cm). 23 were performed open, 43 laparoscopically, and 6 with an intended robotic approach. Median follow-up was 9.3 years.Robotic had the shortest length of stay (LOS) (p-value 0.01), then laparoscopic (p-value 0.00004), then open. The estimated blood loss (EBL) ranged from 5 to 500 mL (median 50 mL). The median LOS was two days.Intra-operative complication rate was 1.4 % and readmission within 30 days occurred in 2.8 %. Out of 72 patients, 6.8 % needed hormone replacement; of the 14 patients with contralateral adrenalectomy, 28.6 % needed replacement. ConclusionPA appears to be safe with both laparoscopic and robotic-assisted techniques with superior perioperative outcomes. The functional results of PA prevent most patients from requiring ongoing steroid replacement treatment and recurrence rates were low. PA should be advised for more frequent use as the preferred treatment method of choice. Key messagePartial adrenalectomies' perioperative and long-term outcomes over a median 9.3 year follow-up emphasized its safety and efficacy with 95 % CI of (2.7 cm, 3.6 cm) for masses with adrenal sufficiency post-resection. Additionally, as healthcare institutions decide whether to invest in surgical robots, robotic approach's outperformance of laparoscopic and open on LOS may be counterbalanced by laparoscopic's strong performance in low EBL.

Adrenal Volume Quantitative Visualization Tool by Multiple Parameters and an nnU-Net Deep Learning Automatic Segmentation Model.

Abnormalities in adrenal gland size may be associated with various diseases. Monitoring the volume of adrenal gland can provide a quantitative imaging indicator for such conditions as adrenal hyperplasia, adrenal adenoma, and adrenal cortical adenocarcinoma. However, current adrenal gland segmentation models have notable limitations in sample selection and imaging parameters, particularly the need for more training on low-dose imaging parameters, which limits the generalization ability of the models, restricting their widespread application in routine clinical practice. We developed a fully automated adrenal gland volume quantification and visualization tool based on the no new U-Net (nnU-Net) for the automatic segmentation of deep learning models to address these issues. We established this tool by using a large dataset with multiple parameters, machine types, radiation doses, slice thicknesses, scanning modes, phases, and adrenal gland morphologies to achieve high accuracy and broad adaptability. The tool can meet clinical needs such as screening, monitoring, and preoperative visualization assistance for adrenal gland diseases. Experimental results demonstrate that our model achieves an overall dice coefficient of 0.88 on all images and 0.87 on low-dose CT scans. Compared to other deep learning models and nnU-Net model tools, our model exhibits higher accuracy and broader adaptability in adrenal gland segmentation.

Amenorrhea as a presentation of Cushing's syndrome.

Menstrual cycle abnormalities are common in premenopausal females with Cushing's syndrome, although the underlying mechanism is poorly understood. Signs and symptoms found in Cushing's syndrome overlap with polycystic ovarian syndrome (PCOS). The patient is a 33-year-old female previously diagnosed by a gynecologist with PCOS and treated with oral contraceptive pills (OCPs) for 2 years. She then discontinued her OCPs without consulting a clinician, resulting in amenorrhea for 6 months, for which she presented. She also had symptoms of depression and anxiety but had no other signs and symptoms of Cushing's syndrome, except a plethoric face. Initial lab work showed evidence of central hypogonadism (low luteinizing hormone, follicle-stimulating hormone, and estrogen), so a complete anterior pituitary hormone workup was done. Her thyroid-stimulating hormone was also low with a low free T4 level. Prolactin level was normal, but surprisingly, her AM cortisol level was high. The Cushing's syndrome workup revealed non-suppressed cortisol after a 1 mg dexamethasone suppression test and positive 24-h urine cortisol with suppressed adrenocorticotrophic hormone. A CT scan of her adrenal glands revealed a left adrenal adenoma. She underwent a left adrenalectomy, after which her menstrual cycles became regular again, and pituitary function has recovered. In Cushing's syndrome, female patients can have menstrual abnormalities due to the high cortisol levels, which can affect gonadotrophin levels. We encourage clinicians to include Cushing's syndrome in the differential diagnosis of patients with central hypogonadism.

Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). This is a single-center cohort study. Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P = .002). Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.