Adrenal Disease Research Articles

Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease.

Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD. A total of 11 serum steroids in adrenal CS (n=13) and CD (n=15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with t-tests. The sensitivity and specificity of DHEA-S ratios<0.40 were 92.31% (95% CI 64.0%-99.8%) and 93.33% (95% CI 68.1%-99.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios<0.18 were 100% (95% CI 75.3%-100.0%) and 100% (95% CI 78.2%-100.0%), respectively, in identifying adrenal CS. Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.

The relation between vitamin D insufficiency and thyroid hormones in Iraqi women living in Al-Khalidiya, Anbar Province

Background: Vitamin D insufficiency is a worldwide issue in all age groups. It wasdiscovered that vitamin D insufficiency is linked to autoimmune disorders such as Irritablebowel illness, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, andrheumatoid arthritis. Vitamin D is also connected to the development of thyroid autoimmunedisease and plays an important role in endocrinopathies including type 1 and type 2 diabetes,adrenal diseases, and polycystic ovarian syndrome.Materials and methods: 100 samples were collected for women from Al-Khalidiya city inAnbar province (50 samples likely to have thyroid problems, 50 healthy samples). The levelsof vitamin D and thyroid hormones were measured using A Minividus system (whichcombines a two-step enzyme sands assay with an ELFA, or End Fluorescent DetectionMethod).Results: The current findings revealed that there are significant variations in vitamin D andT4 levels between patients and healthy controls ( P-value 0.05). There is also a positiveassociation between vitamin D levels and T4 (r = 0.378, P-value = 0.007), as well as anegative correlation between vitamin D levels and TSH (r = -0.373, P-value = 0.008).Conclusion: According to our result, Individuals with hypothyroidism in Alkhaldia have avitamin D3 deficiency. In addition, blood vitamin D levels show a positive correlation with T4and a negative correlation with TSH levels. To avoid developing osteoporosis ifhypothyroidism persists, all hypothyroid Iraqi patients should be checked for Vitamin Ddeficiency.

O159 Nonselective alpha blockade alone is associated with a significant decrease in ICU/CCU requirement following phaeochromocytoma resection

Abstract Introduction Preoperative treatment with alpha blockade is key to optimisation of patients with phaeochromocytoma. Beta blockers may be employed after optimal alpha blockade to prevent reflex tachycardia. The principle of treatment is to avoid severe intraoperative hypertension or hypotension, but the optimal perioperative regimen is unclear. Recent studies have suggested that dual blockade may increase the rate of intraoperative haemodynamic instability We hypothesized that nonselective alpha blockade alone, without addition of beta blockers, would reduce the need for postoperative ICU/CCU supportive care. Methods A retrospective study of all patients undergoing pheochromocytoma/paraganglioma resection between 1998 and 2022 was performed. Patients were categorized into two cohorts: Group 1 patients received alpha and beta blockers preoperatively while Group 2 patients received nonselective alpha blockade alone. The primary endpoint was the need for ICU/CCU support. Results Of 40 patients identified, adrenalectomy was performed in 36. Median age at resection was similar for both groups (63 v 56 years). Of 22 Group 1 patients 8 (36.4%) required ICU/CCU admission due to haemodynamic instability, (MLS 1.22 days) compared to 3 (21.4%) of the 14 Group 2 (MLS 0.21, p=0.035; one-tailed Two-Sample t-test assuming unequal variance). Median maximum diameter of lesions in Group 1 was 5.4cm, while Group 2 was 4.2cm. In Group 1 59% showed right adrenal disease (n=13), Group 2 43% (n=6). Conclusion Our study suggests that nonselective alpha blocker alone, without the addition of beta blockers, is associated with a significantly decreased requirement for post-operative support in the ICU or CCU following pheochromocytoma resection.

Co-existence of an adrenal mass and Cushing's disease: a diagnostic challenge

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A retrospective study of the range of cutaneous clinical and histological features of erythema multiforme in five ferrets (Mustela putorius furo).

Erythema multiforme (EM) is an uncommon cutaneous reaction pattern characterised by panepidermal keratinocyte apoptosis with lymphocytic satellitosis, and is reported in domestic animal species, livestock and rarely ferrets. The aim of this study was to analyse the spectrum of cutaneous clinical and histological features in ferrets with EM and to evaluate history and treatment outcomes. Five client-owned ferrets with biopsy-confirmed EM. Retrospective review of electronic medical records and histopathological reports from 2002 to 2021. Tissue blocks, haematoxylin and eosin re-cuts, and unstained slides were collected to review EM lesions and evaluate for infectious agents with special stains. Immunohistochemical staining was performed to assess cases for viral pathogens. Panepidermal cytotoxic dermatitis consistent with EM was identified in all cases and involved haired skin in four of five and mucous membranes in one of five ferrets. Skin lesions included variably pruritic alopecia, erythema, scaling, crusts and erosions/ulcerations. Histological features included primarily parakeratotic hyperkeratosis, panepidermal keratinocyte apoptosis, lymphocytic satellitosis and interface dermatitis. Superficial colonisation by bacteria, yeasts or by both was a common finding. Four of five ferrets had concurrent adrenal disease, one of which had resolution of skin lesions with deslorelin acetate treatment. Awareness of the distinct clinical and histological features is key to the diagnosis of EM in ferrets. Clinical resolution was observed with gonadotropin-releasing hormone agonists in two cases, suggesting that adrenal disease should be ruled out as a potential trigger of EM in ferrets.

Surgical approaches to the adrenal gland.

Review the literature on the surgical management of adrenal diseases, highlighting the various surgical approaches and their respective pros and cons. Minimally invasive adrenalectomy is commonly used for small and benign adrenal tumors, whereas open adrenalectomy is preferred for larger tumors and primary adrenal malignancy. Although minimally invasive adrenalectomy results in shorter recovery and fewer complications compared with open, the latter offers better oncologic outcomes in the setting of primary adrenal malignancy. Adrenalectomy is performed transabdominally or retroperitoneoscopically, both yielding equivalent results and recovery. Traditional laparoscopic or robotic equipment can be utilized for either minimally invasive approach. Subtotal adrenalectomy may be appropriate for patients with genetically associated pheochromocytoma to preserve cortical function and reduce the risk of adrenal insufficiency. However, the potential benefits of sparing adrenal function must be weighed against the risk of recurrence. Adrenalectomy is becoming increasingly common worldwide. For benign and small adrenal tumors, minimally invasive adrenalectomy is generally considered the standard approach, while open adrenalectomy is preferred for primary adrenal malignancy and larger tumors. Subtotal adrenalectomy may be appropriate for patients with bilateral adrenal pheochromocytoma, as it can reduce the need for lifelong glucocorticoid dependency.

A Case of Clinically Silent Giant Right Pheochromocytoma

Patients with pheochromocytoma are typically symptomatic. Hypertension is the most common sign of pheochromocytoma. Clinically silent giant pheochromocytoma is a rare adrenal disease; complete resection is the only curative treatment. Due to the serious surgical risk, successful resection is very difficult. We report a case of 70-year-old- female with giant pheochromocytoma, which was successfully resected. There were no intraoperative and postoperative complications. We analyze and report our experience.

Establishment and validation of a nomogram for predicting perioperative complications of retroperitoneal laparoscopic adrenalectomy.

While laparoscopic adrenalectomy (LA) represents a gold standard for treating most adrenal lesions, no effective visual model for the prediction of perioperative complications of retroperitoneal laparoscopic adrenalectomy (RLA) exists. A retrospective study was conducted involving all consecutive patients underwent unilateral RLA for adrenal disease from January 2012 to December 2021. The entire cohort was randomly divided into 2 subsets (70% of the data for training, 30% for validation). Subsequently, a Least Absolute Shrinkage Selection Operator (LASSO) regression was performed to select the predictor variables, which were further consolidated via random forest (RF) and Boruta algorithm. Then the nomogram was established using the bivariate logistic regression analysis. Eventually, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate discrimination, calibration and clinical usefulness of the model, respectively. A total of 610 patients underwent unilateral RLA for adrenal diseases were enrolled. After machine learning analyses, a weighted nomogram was established with 7 factors associated with complications including operative time, lesion laterality, intraoperative blood loss, pheochromocytoma, body mass index (BMI) and 2 preoperative comorbidities [respiratory diseases, cardiovascular diseases (CVD)]. The model displayed a fine calibration curve for perioperative complications evaluation in both the training dataset (P=0.847) and validation dataset (P=0.248). ROC with area under the curve (AUC) revealed excellent discrimination in the training dataset (0.817, 95% CI: 0.758-0.875) and validation dataset (0.794, 95% CI: 0.686-0.901). DCA curves showed that using this nomogram provided a more net benefit where threshold probabilities lay in the range of 0.1 to 0.9. An effective nomogram that incorporating 7 predictors was established in this study to identify patients at high risk of perioperative complications for RLA. It would contribute to the improvement of perioperative strategy due to its accuracy and convenience.

A hyperaldosteronism subtypes predictive model using ensemble learning

This study aimed to develop a machine-learning algorithm to diagnose aldosterone-producing adenoma (APA) for predicting APA probabilities. A retrospective cross-sectional analysis of the Japan Rare/Intractable Adrenal Diseases Study dataset was performed using the nationwide PA registry in Japan comprised of 41 centers. Patients treated between January 2006 and December 2019 were included. Forty-six features at screening and 13 features at confirmatory test were used for model development to calculate APA probability. Seven machine-learning programs were combined to develop the ensemble-learning model (ELM), which was externally validated. The strongest predictive factors for APA were serum potassium (s-K) at first visit, s-K after medication, plasma aldosterone concentration, aldosterone-to-renin ratio, and potassium supplementation dose. The average performance of the screening model had an AUC of 0.899; the confirmatory test model had an AUC of 0.913. In the external validation, the AUC was 0.964 in the screening model using an APA probability of 0.17. The clinical findings at screening predicted the diagnosis of APA with high accuracy. This novel algorithm can support the PA practice in primary care settings and prevent potentially curable APA patients from falling outside the PA diagnostic flowchart.

Acupuncture for Hindlimb Lameness in a Ferret

A geriatric ferret with a complicated medical history (adrenal disease, kidney disease, hindlimb lameness/weakness, chronic diarrhea, urinary incontinence) was presented for traditional Chinese veterinary medicine (TCVM) evaluation. A thorough conventional medical work-up had been performed but financial resources were unavailable for specialty referral. The owner, however, still wanted her pet to have a good quality of life for as long as reasonably possible. The ferret was a good candidate for acupuncture given that TCVM theory explained many of the clinical abnormalities. The owner’s most significant concern was the patient’s mobility and pain; therefore, the TCVM Patterns of Kidney Qi Deficiency and local Qi Stagnation were the focus of the initial TCVM visits. Aside from the deslorelin implant, the owner elected to discontinue all traditional medications. Improvements noted in the patient’s quality of life correlated with the acupuncture therapy received. Over a 2-month period and 5 acupuncture sessions, the patient’s mobility and urinary incontinence improved and complete resolution of the diarrhea occurred. At the conclusion of care for this patient, a recommendation for continuing TCVM was made with acupuncture treatments every 1-2 months along with disease monitoring with conventional diagnostics. This case is an excellent example of the medical benefits of acupuncture in an exotic companion mammal.

Automated Adrenal Gland Disease Classes Using Patch-Based Center Symmetric Local Binary Pattern Technique with CT Images.

Incidental adrenal masses are seen in 5% of abdominal computed tomography (CT) examinations. Accurate discrimination of the possible differential diagnoses has important therapeutic and prognostic significance. A new handcrafted machine learning method has been developed for the automated and accurate classification of adrenal gland CT images. A new dataset comprising 759 adrenal gland CT image slices from 96 subjects were analyzed. Experts had labeled the collected images into four classes: normal, pheochromocytoma, lipid-poor adenoma, and metastasis. The images were preprocessed, resized, and the image features were extracted using the center symmetric local binary pattern (CS-LBP) method. CT images were next divided into 16 × 16 fixed-size patches, and further feature extraction using CS-LBP was performed on these patches. Next, extracted features were selected using neighborhood component analysis (NCA) to obtain the most meaningful ones for downstream classification. Finally, the selected features were classified using k-nearest neighbor (kNN), support vector machine (SVM), and neural network (NN) classifiers to obtain the optimum performing model. Our proposed method obtained an accuracy of 99.87%, 99.21%, and 98.81% with kNN, SVM, and NN classifiers, respectively. Hence, the kNN classifier yielded the highest classification results with no pathological image misclassified as normal. Our developed fixed patch CS-LBP-based automatic classification of adrenal gland pathologies on CT images is highly accurate and has low time complexity [Formula: see text]. It has the potential to be used for screening of adrenal gland disease classes with CT images.

The use of ultrasonographic adrenal dimensions and the adrenal dimension-to-aorta ratio in the diagnosis of benign and malignant adrenal diseases in dogs.

Ultrasound (US) is a useful tool for detecting adrenal abnormalities. However, a definite reference range differentiating normal and diseased adrenal glands in dogs of varying body sizes is still lacking. The organ dimension-to-aorta (Ao) ratio of the dogs is correlated with their body weight (BW). Therefore, this study aimed to investigate the adrenal dimensions, including adrenal pole thickness and adrenal length, as well as the adrenal dimension-to-Ao ratio, to differentiate between dogs with normal, benign lesions such as pituitary-dependent hyperadrenocorticism (PDH) and malignant invasive adrenal tumors. The medical records and US images of 39 dogs that were either normal (normal) (n = 15) or affected by PDH (n = 15) or malignant invasive adrenal tumors (tumor) (n = 9) were retrieved in this study. All the dogs had a transabdominal US on the sagittal plane. The adrenal dimensions and luminal Ao diameter at the peak of the systolic phase were recorded. The average adrenal dimensions, including the adrenal dimension-to-Ao ratio, were compared among the groups. Most of the dogs in each group were small-breed dogs with comparable ages, BW, and Ao values. Both adrenal dimensions and the adrenal dimension-to-Ao ratio were significantly lower in the normal group than in the PDH and tumor groups. To differentiate the PDH group from the tumor group, adrenal dimensions of pole thickness and length were more appropriate than the adrenal dimension-to-Ao ratio. Adrenal dimensions and the adrenal dimension-to-Ao ratio can be used to diagnose adrenal diseases. However, in small-breed dogs, adrenal dimensions are suitable for differentiating PDH from tumor groups. Further research is required with a larger sample size and a wider range of canine body sizes.

Adrenal Dysfunction in Mitochondrial Diseases.

Cortisol is central to several homeostatic mechanisms including the stress and immune response. Adrenal insufficiency and impaired cortisol production leads to severe, potentially fatal disorders. Several fundamental stages of steroidogenesis occur within the mitochondria. These dynamic organelles not only contribute ATP for steroidogenesis, but also detoxify harmful by-products generated during cortisol synthesis (reactive oxygen species). Mutations in nuclear or mitochondrial DNA that impair mitochondrial function lead to debilitating multi-system diseases. Recently, genetic variants that impair mitochondrial function have been identified in people with isolated cortisol insufficiency. This review aimed to clarify the association between mitochondrial diseases and adrenal insufficiency to produce cortisol. Mitochondrial diseases are rare and mitochondrial diseases that feature adrenal insufficiency are even rarer. We identified only 14 cases of adrenal insufficiency in people with confirmed mitochondrial diseases globally. In line with previous reviews, adrenal dysfunction was most prevalent in mitochondrial deletion syndromes (particularly Pearson syndrome and Kearns-Sayre syndrome) and with point mutations that compromised oxidative phosphorylation. Although adrenal insufficiency has been reported with mitochondrial diseases, the incidence reflects that expected in the general population. Thus, it is unlikely that mitochondrial mutations alone are responsible for an insufficiency to produce cortisol. More research is needed into the pathogenesis of adrenal disease in these individuals.

S-13-2: PATHOLOGY UPDATE OF CUSHING'S SYNDROME AND PRIMARY ALDOSTERONISM ACCORDING TO WHO 2022

New pathology classification of endocrine and neuroendocrine tumours is currently being updated as one of WHO classification of tumours version 5. Not only pathologists but also clinicians involved in the clinical management of those patients should be familiar with novel classification including their new concepts. Therefore in this presentation, we will introduce newly updated concepts of adrenocortical diseases associated with Cushing's syndrome and primary aldosteronism. In Cushing's syndrome, primary bilateral nodular adrenal cortical disease has turned out to harbor multiple independent clonal proliferations and the term hyperplasia should not be used in these adrenocortical disorders. Hyperplasia should be only reserved for those associated with ACTH overproduction from pituitary or others. Various somatic and/or genomic mutations of the genes involved in intracellular signaling pathways have been reported in almost all bilateral micronodular adrenal cortical disease and the great majority of bilateral macronodular adrenal cortical disease associated with Cushing's syndrome. For instance, bilateral micronodular adrenocortical disease harbors pathogenic germline mutations resulting in the activation of the protein kinase A or PKA pathway including PRKAR1A, PRKAR1A, PRKACA, PDE11A, PDE8B and 2p16 CNC2 locus alterations. On the other hand, bilateral macronodular adrenal cortical disease has been linked to several germline alterations including ARMC5, MEN1, FH, APC and others.Clinical significance of those genetic abnormalities above including potential therapeutic manipulation is being studied at this juncture. In primary aldosteronism, the introduction of CYP11B2 has enormously contributed to the establishment of new concept of adrenocortical pathology. Primary aldosteronism can be generally classified into two categories. The one in which aldosterone production diffusely occurs in the hyperplastic zona glomerulosa and the other harboring localized aldosterone production. The former is generally bilateral and the latter unilateral or bilateral. The latter category also includes both nodule and adenoma, which could be differentiated according to the status of intra-lesional distribution of CYP11B2. CYP11B2 positive localized proliferation of the zona glomerulosa cells is frequently detected in non hypertensive subject and should be termed aldosterone producing nodules (APN) rather than aldosterone producing cell clusters (APCC). The potential cascade from these aldosterone producing nodules in normal subject to those associated with clinically overt primary aldosteronism is being investigated including the possible concept of pre- or subclinical primary aldosteronism.

Laboratory Diagnosis of Thyroid and Adrenal Disease.

Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward, hypothyroidism and naturally occurring Cushing's syndrome (NOCS) are more complicated. In a patient with compatible clinical signs, a single increased tT4 is enough to confirm hyperthyroidism, but a low tT4 alone is never enough to confirm hypothyroidism. A flatline result (post-stimulation cortisol <2 ug/dL) on an ACTH stimulation test (ACTHst) confirms hypoadrenocorticism, but not all dogs with NOCS have increased ACTHst results. This article explains which diagnostics should be pursued for these endocrinopathies, and how to interpret them.

Prospects for development of laparoscopic surgery in the Central Federal District of the Russian Federation

To analyze the achievements of laparoscopic surgery in the Central Federal District of Russia and outline perspective trends for further application. The study included adult patients with abdominal surgical diseases hospitalized in general surgical departments of the Central Federal District between 2014 and 2021. We analyzed the prevalence of elective and emergency laparoscopic surgeries. Incidence and results of laparoscopic interventions between 2018 and 2021 were estimated considering primary statistical data presented in the annual collections of the Chief Surgeon of the Ministry of Health of Russia «Surgical care in the Russian Federation». The absolute number of laparoscopic surgeries in the Central Federal District increased from 23.686 to 80.489 (by 3.4 times) between 2014 and 2021. The annual number of elective laparoscopic surgeries exceeded the number of emergency ones up to 2019. In 2020-2021, this situation changed in favor of emergency abdominal procedures. Laparoscopic surgeries are the most common for in acute cholecystitis (71.06-81.10% of all laparoscopic interventions annually) and acute appendicitis (46.85-55.60%). In 2020 and 2021, the absolute number of laparoscopic appendectomies exceeded the number of laparoscopic cholecystectomies. These values are lower for perforated ulcers (15.44-20.39%) and acute pancreatitis (32.40-36.71%). Laparoscopic operations are rare for acute intestinal obstruction, strangulated hernia and ulcerative gastroduodenal bleeding. In elective surgery, high availability of laparoscopic surgeries was noted in patients with cholelithiasis (89.40-93.78%), hiatal hernia (62.12-77.27%) and adrenal gland diseases (64.23-87.25%). The most intensive increment of availability (by 2.4 times) was noted for inguinal hernia from minimum level (10.98%) in 2018 to 26.00% in 2021. Mortality after some laparoscopic operations decreased in comparison with laparotomy by 12-45 times (2018-2021). However, this aspect and results of laparoscopic surgeries in case of delayed hospitalization require additional study. Analysis of laparoscopic surgery showed the timeliness of beginning and development of this direction In Russia. The prospect of further development of laparoscopic surgery for abdominal diseases is determined by modern trends. These are increase in the number of laparoscopic operations for acute appendicitis, acute cholecystitis and perforated ulcers, as well as higher number of early (after admission) operations.

PS-C21-5: EFFICACY OF SWITCHING FROM EPLERENONE TO ESAXERENONE FOR THE TREATMENT OF PRIMARY ALDOSTERONISM

Background: Mineralocorticoid receptor (MR) antagonist is the first choice for medical therapy for primary aldosteronism (PA) due to bilateral adrenal disease. However, there are many cases of PA in which blood pressure control are inadequate and/or suppression of renin are insufficiently released even under the maximum dose of eplerenone (EPL) approved in Japan. In this study, we investigated the effect of switching to the novel MR antagonist Esaxerenone (ESX) in PA patients whose renin suppression was not released even under the maximum dose of EPL. Methods: Twenty-seven patients (age; 53 ± 10 years, male/female; 14/13) who were diagnosed with PA at our hospital and showed plasma renin activity (PRA) &lt; 1.0 ng/mL/hr even under EPL 100 mg/day were switched to ESX. We investigated changes in blood pressure, PRA, plasma aldosterone concentration (PAC), blood biochemical findings, and concomitant antihypertensive agents in these patients for 12 months. Results: Systolic and diastolic blood pressure decreased significantly from 1 month (133 ± 12/84 ± 8 mmHg) to 12 months (127 ± 10/80 ± 9 mmHg) compared to before switching to ESX (140 ± 16/88 ± 11 mmHg), whereas the rate of concomitant use of other antihypertensive agents did not change (44.4% ¡ú 45.0%). PRA (0.5 ± 0.4 ng/mL/hr) increased significantly from 6 months (0.6 ± 0.4 ng/mL/hr) to 12 months (0.8 ± 0.6 ng/mL/hr). PAC (191 ± 83 ¡ú 188 ± 110 pg/mL), serum potassium (4.3 ± 0.3 ¡ú 4.4 ± 0.4 mEq/L), AST (20 ± 6 ¡ú 22 ± 4 U/L), ALT (21 ± 11 ¡ú 21 ± 5 U/L) and γGTP (34 ± 41 ¡ú 38 ± 34 U/L) did not change. Estimated GFR (78 ± 14 ¡ú 70 ± 15 mL/min/1.73m2) gradually decreased. Conclusions: These results suggest that ESX is a more potent antagonist of MR with equivalent safety to EPL in the management of PA.

Establishment and validation of a nomogram for predicting the surgical difficulty of lateral retroperitoneal laparoscopic adrenalectomy.

Lateral retroperitoneal laparoscopic adrenalectomy (LRLA) is widely performed for the resection of adrenal disorders, but when larger and more malignant lesions are involved, the difficulty of LRLA increases. We aimed to develop and evaluate a predictive model for the surgical difficulty of LRLA. A retrospective, observational, single-center study was performed involving all consecutive cases of unilateral RLA for adrenal disease from 2012.01 to 2021.12. Cases were randomly divided into training and validation cohorts (split ratio =7:3), then the least absolute shrinkage and selection operator (LASSO) regression was applied to reduce data dimension and select predictors. Multivariate logistic regression followed to develop the prediction nomogram for the surgical difficulty of LRLA. Finally, receiver operating characteristic (ROC) curve, calibration curve plot and decision curve analysis (DCA) were used to evaluate the nomogram's discrimination, calibration, and clinical usefulness, respectively. A total of 621 cases were enrolled with a median age of 53 years and a median tumor diameter of 1.7 cm. After LASSO regression analysis, surgeon's experience, tumor diameter, resection procedure, histological type, patient's sex and body mass index (BMI) were identified to establish the nomogram. The model displayed good discrimination with area under the curve (AUC) in both the training cohort (0.754, 95% CI: 0.701-0.806) and validation cohort (0.742, 95% CI: 0.646-0.838). Additionally, excellent calibration curves were revealed for surgical difficulty evaluation in both the training cohort (P=0.999) and validation cohort (P=0.444). DCA results indicated the prediction model was clinically useful. Our novel and effective predictive model can be used to assess the individual surgical difficulty of LRLA. By stratifying patients at risk of having a difficult LRLA for adrenal disease, the model could contribute to improvements in perioperative strategy and therapy.

An adrenal incidentaloma that had appeared to produce dehydroepiandrosterone-sulfate in excess before immunohistochemical study of the tumor.

Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110-120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 μg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060-4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3β-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11β-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 μg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.