Updates on WHO 5th edition classification, molecular characteristics and tumor microenvironment of adrenocortical carcinomas.

Discerning malignancy in adrenocortical tumors is clinically pivotal in the management of patients but has also been one of the most difficult areas in both clinical and pathology settings. The recently published WHO 5th edition "Endocrine and Neuroendocrine Tumours" recommends a diagnostic algorithm employing not only one but several proposed histopathological criteria-including the Weiss criteria and its revision and the Helsinki criteria-in addition to the Reticulin algorithm, the Ki-67 proliferative index, and others depending upon their histopathological features. On the other hand, the risk classification proposed by ENSAT (European Network of Study for Adrenal Tumors) in 2018 was primarily based on the Ki-67 proliferative index of carcinoma cells, especially focusing on whether or not postoperative or adjuvant chemotherapy could be administered.

Cost-effectiveness analysis of segmental adrenal venous sampling with radiofrequency ablation for primary aldosteronism in Japan.

Purpose: The purpose of this study was to evaluate the cost-effectiveness of comprehensive treatment strategy, including segmental adrenal venous sampling (sAVS) and radiofrequency ablation (RFA), versus medication-only strategy for primary aldosteronism.

Materials And Methods: A Markov decision model was developed to compare the cost-effectiveness of a comprehensive treatment strategy and a medication-only strategy for 50-year-old men and women with stage I-III hypertension. The comprehensive treatment strategy included aldosterone/renin ratio measurement, two loading tests, computed tomography, sAVS, drugs, surgery, and RFA.

Screening Cutoff Values for the Detection of Aldosterone-Producing Adenoma by LC-MS/MS and a Novel Noncompetitive CLEIA.

Context: Detecting patients with surgically curable aldosterone-producing adenoma (APA) among hypertensive individuals is clinically pivotal. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method of measuring plasma aldosterone concentration (PAC) because of the inaccuracy of conventional chemiluminescent enzyme immunoassay (CLEIA). However, LC-MS/MS is expensive and requires expertise.

The Spectrum of Dysregulated Aldosterone Production: An International Human Physiology Study.

Context: Primary aldosteronism is a form of low-renin hypertension characterized by dysregulated aldosterone production.

Objective: To investigate the contributions of renin-independent aldosteronism and ACTH-mediated aldosteronism in individuals with a low-renin phenotype representing the entire continuum of blood pressure.

Design/participants: Human physiology study of 348 participants with a low-renin phenotype with severe and/or resistant hypertension, hypertension with hypokalemia, elevated blood pressure and stage I/II hypertension, and normal blood pressure.

Histopathological analysis of tumor microenvironment in adrenocortical carcinoma: Possible effects of in situ disorganized glucocorticoid production on tumor immunity.

Adrenocortical carcinoma (ACC) patients with glucocorticoid excess have been reported to be associated with decreased tumor-infiltrating immune cells, but the effects of in situ glucocorticoid production on tumor immunity have remained unknown. In addition, ACC was also known to harbor marked intra-tumoral heterogeneity of steroidogenesis or disorganized steroidogenesis. Therefore, in this study, we immune-profiled tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) and pivotal steroidogenic enzymes of glucocorticoid biosynthesis (CYP17A and CYP11B1) to explore the potential effects of in situ glucocorticoid production and intra-tumoral heterogeneity/disorganized steroidogenesis on tumor immunity of ACC.

Identifying primary aldosteronism patients who require adrenal venous sampling: a multi-center study.

Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited, efforts have been made to develop strategies to bypass it. However, it has so far proven unsuccessful in applying clinical practice, partly due to heterogeneity and missing values of the cohorts.

Transvenous Radiofrequency Catheter Ablation for an Aldosterone-Producing Tumor of the Left Adrenal Gland: A First in Human Case Report.

Purpose: To describe a novel technique of transvenous radiofrequency catheter ablation of an aldosterone-producing adenoma (APA) of the left adrenal gland using the GOS System (Japan Lifeline, Tokyo, Japan). Using the GOS system, a flexible radiofrequency tip catheter can be inserted into the adrenal central and tributary veins, the drainers for functional tumors.

Materials And Methods: An APA at the left adrenal gland, which was diagnosed by segmental adrenal venous sampling following administration of 0.

Utility of Carbon Dioxide Venography and Intraprocedural CT for Adrenal Venous Sampling in Patients with an Allergy to Iodinated Contrast Media.

Purpose: To assess the diagnostic performance of carbon dioxide (CO) and intraprocedural unenhanced computed tomography (CT) for adrenal venous sampling (AVS) (CO-intraprocedural unenhanced CT-AVS) in patients with primary aldosteronism (PA) and a history of iodine contrast medium allergy.

Materials And Methods: CO-intraprocedural unenhanced CT-AVS was performed in 18 patients with iodine contrast media allergies at the authors' hospital between December 2015 and January 2021. CT and noncontrast magnetic resonance angiography were used to evaluate the preoperative adrenal vein anatomy.

Impact of Adrenalectomy on Diastolic Cardiac Dysfunction in Patients with Primary Aldosteronism.

Poor prognostic cardiac function is known among some patients with primary aldosteronism (PA). However, studies with echocardiograms on whether the normalization of aldosterone after laparoscopic adrenalectomy (LADX) improves myocardial hypertrophy and diastolic cardiac dysfunction have been inadequate. Between August 2009 and December 2021, 147 patients with unilateral PA who underwent pre- and post-LADX echocardiography at a single center were enrolled in this retrospective study.

Bipolar Radiofrequency Ablation of the Adrenal Gland: In Vivo and Ex Vivo Experiments.

Laparoscopic adrenalectomy is currently the standard treatment modality for unilateral aldosterone-producing adenoma (APA); however, a less-invasive treatment is needed for its treatment. A new bipolar ablation system that poses a lower risk of complications has been recently developed. This study aimed to evaluate the safety and performance of a novel bipolar radiofrequency ablation (RFA) system for the treatment of APAs.

Marked reduction of proteinuria after removal of a growth hormone-producing pituitary adenoma in a patient with focal segmental glomerulosclerosis: a case report and literature review.

Focal segmental glomerulosclerosis is a rare complication of acromegaly. A 74-year-old man was found to have acromegaly features such as enlargement of the forehead, nose, and hands. Laboratory tests showed a urine protein/creatinine ratio of 3.

Safety and feasibility of radiofrequency ablation using bipolar electrodes for aldosterone-producing adenoma: a multicentric prospective clinical study.

Evaluation of feasibility and safety of percutaneous radiofrequency ablation using bipolar radiofrequency devices in a prospective multicenter cohort of patients with benign aldosterone-producing adenoma. A total of five institutions participated. CT-guided percutaneous RFA was performed for patients diagnosed as APA.

Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism.

Aldosterone-producing adenoma (APA) is histologically composed of clear and compact tumor cells. KCNJ5- mutated APAs were reported to be associated with higher plasma aldosterone concentration and more abundant clear tumor cells containing lipid droplets than non-KCNJ5- mutated APAs. However, the association among cholesterol uptake and/or synthesis, cellular morphology and genotypes has remained unknown.

The Association of Cholesterol Uptake and Synthesis with Histology and Genotype in Cortisol-Producing Adenoma (CPA).

Cortisol-producing adenoma (CPA) is composed of clear and compact cells. Clear cells are lipid abundant, and compact ones lipid poor but associated with higher production of steroid hormones. mutation ( mt) in CPA patients was reported to be associated with more pronounced clinical manifestation of Cushing's syndrome.

Visualization of calcium channel blockers in human adrenal tissues and their possible effects on steroidogenesis in the patients with primary aldosteronism (PA).

Voltage-gated L-type calcium channel (CaV) isoforms are well known to play pivotal tissue-specific roles not only in vasoconstriction but also in adrenocortical steroidogenesis including aldosterone biosynthesis. Alpha-1C subunit calcium channel (CC) (CaV1.2) is the specific target of anti-hypertensive CC blockers (CCBs) and its Alpha-1D subunit (CaV1.

Laparoscopic Adrenalectomy Is Beneficial for the Health-Related Quality of Life of Older Patients with Primary Aldosteronism.

Objective: Laparoscopic adrenalectomy (LADX) improves hypertension in patients with primary aldosteronism (PA). However, the antihypertensive impact of LADX appears restricted in older patients with PA. In this study, we evaluated the impact of LADX in older patients focusing on the health-related quality of life (HRQoL).

Renal Injuries in Primary Aldosteronism: Quantitative Histopathological Analysis of 19 Patients With Primary Adosteronism.

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Cellular Senescence in Human Aldosterone-Producing Adrenocortical Cells and Related Disorders.

In situ cortisol excess was previously reported to promote cellular senescence, a cell response to stress, in cortisol-producing adenomas (CPA). The aim of this study was to explore senescence pathways in aldosterone-producing cells and related disorders, and the influence of aldosterone overproduction on in situ senescence. We analyzed 30 surgical cases of aldosterone-producing adenoma (APA), 10 idiopathic hyperaldosteronism (IHA) and 19 normal adrenals (NA).

Pathology of Aldosterone Biosynthesis and its Action.

Aldosterone plays pivotal roles in renin-angiotensin-aldosterone system in order to maintain the equilibrium of liquid volume and electrolyte metabolism. Aldosterone action is mediated by both mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Its excessive actions directly induced tissue injuries in its target organs such as myocardial and vascular fibrosis in addition to chronic kidney diseases.

The Genotype-Based Morphology of Aldosterone-Producing Adrenocortical Disorders and Their Association with Aging.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with an increased incidence of cardiovascular events. PA itself is clinically classified into the following two types: unilateral PA, mostly composed of aldosteroneproducing adenoma (APA); and bilateral hyperaldosteronism, consisting of multiple aldosterone-producing micronodules (APMs) and aldosterone-producing diffuse hyperplasia. Histopathologically, those disorders above are all composed of compact and clear cells.

The Potential of Computed Tomography Volumetry for the Surgical Treatment in Bilateral Macronodular Adrenal Hyperplasia: A Case Report.

Although adrenal resection is a major option to control hypercortisolemia in patients with bilateral macronodular adrenal hyperplasia, a predictive method for postoperative cortisol production has not been established. A 53-year-old man with ulcerative colitis was referred to our hospital for bilateral multiple adrenal nodules and hypertension. Physical and endocrinological examination revealed inappropriate cortisol production and suppressed secretion of adrenocorticotropic hormone with no typical signs of Cushing's syndrome.

Gender differences in human adrenal cortex and its disorders.

The adrenal cortex plays pivotal roles in the maintenance of blood volume, responsiveness to stress and the development of gender characteristics. Gender differences of human adrenal cortex have been recently reported and attracted increasing interests. Gender differences occur from the developing stage of the adrenal, in which female subjects had more activated stem cells with higher renewal capacity resulting in gender-associated divergent structures and functions of cortical zonations of human adrenal.