Transcriptomics, Epigenetics, and Metabolomics of Primary Aldosteronism

INTRODUCTION Primary aldosteronism (PA) is the most common cause of endocrine hypertension, mainly caused by aldosterone-producing adenomas or hyperplasia; understanding its pathophysiological background is important in order to provide ameliorative treatment strategies. Over the past several years, significant progress has been documented in this field, in particular in the clarification of the genetic and molecular mechanisms responsible for the pathogenesis of aldosterone-producing adenomas (APAs). METHODS Systematic searches of the PubMed and Cochrane databases were performed for all human studies applying transcriptomic, epigenetic or metabolomic analyses to PA subjects. Studies involving serial analysis of gene expression and microarray, epigenetic studies with methylome analyses and micro-RNA expression profiles, and metabolomic studies focused on improving understanding of the regulation of autonomous aldosterone production in PA were all included. RESULTS In this review we summarize the main findings in this area and analyze the interplay between primary aldosteronism and several signaling pathways with differential regulation of the RNA and protein expression of several factors involved in, among others, steroidogenesis, calcium signaling, and nuclear, membrane and G-coupled protein receptors. Distinct transcriptomic and metabolomic patterns are also presented herein, depending on the mutational status of APAs. In particular, two partially opposite transcriptional and steroidogenic profiles appear to distinguish APAs carrying a KCNJ5 mutation from all other APAs, which carry different mutations. CONCLUSIONS These findings can substantially contribute to the development of personalized treatment in patients with PA

PCOS remains a diagnosis of exclusion:a concise review of key endocrinopathies to exclude

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS

Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature.</p> <p>Case presentation</p> <p>A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease.</p> <p>Conclusions</p> <p>Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.</p

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy

International multicenter survey on screening and confirmatory testing in primary aldosteronism

Objective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. Design: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. Results: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. Conclusions: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.Metabolic health: pathophysiological trajectories and therap

The clinical significance of adrenal incidentalomas

Background The term adrenal incidentaloma (AI) indicates an adrenal mass lesion &gt;1cm in diameter discovered during testing for conditions unrelated to adrenal disease. The overall prevalence of these lesions ranges between 3% and 10%. Their incidence increases with age, and it is clinically important to identify AI associated with hormonal activity and/or malignant potential. Design A detailed Medline search of all English language articles related to AI was carried out, and the clinical implications related to their hormonal activity and malignant potential are discussed. Results The subclinical hypercortisolism observed in a significant percentage of patients with AI is associated with some of the detrimental effects of continuous autonomous cortisol secretion, including a higher prevalence of hypertension, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus and an increased risk for osteoporotic fractures. However, it remains to be proven whether treatment to reverse subtle glucocorticoid excess is beneficial. Clinically silent phaeochromocytomas and primary adrenal cancer are conditions associated with significantly high morbidity and mortality and require urgent treatment, while the prevalence and clinical significance of autonomous mineralocorticoid secretion are less clearly defined. Size and radiological features are the main predictors of malignant potential. Conclusions Patients harbouring AI should be evaluated for the possibility of malignancy and/or subclinical hypercortisolism which is associated with cardiovascular risk and bone loss. However, in the absence of prospective controlled studies correlating biochemical activity with end-organ complications, the long-term consequences of AI remain uncertain and their management remains largely pragmatic. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation

Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension

Primary hyperaldosteronism (PA) is a well-known cause of hypertension although its exact prevalence amongst patients with apparent essential hypertension has been a matter of debate. A number of recent studies have suggested that mild forms of PA may be relatively common taking into consideration factors that were previously either overestimated or ignored when developing diagnostic tests of PA and when applying these tests into normotensive individuals. The performance characteristics and diagnostic accuracy of such tests are substantially increased when the adrenocorticotrophin effect, inappropriate potassium levels and their application in carefully selected normotensive individuals are considered. In the present review, we critically analyze these issues and provide evidence that several, particularly mild, forms of PA can be effectively identified exhibiting potentially important clinical implications. © 2020 Georg Thieme Verlag. All rights reserved

Cardiac Remodeling in Hypertension: Clinical Impact on Brain, Heart, and Kidney Function

Hypertension is the most common causative factor of cardiac remodeling, which, in turn, has been associated with changes in brain and kidney function. Currently, the role of blood biomarkers as indices of cardiac remodeling remains unclear. In contrast, cardiac imaging, including echocardiography and cardiovascular magnetic resonance (CMR), has been a valuable noninvasive tool to assess cardiac remodeling. Cardiac remodeling during the course of systemic hypertension is not the sole effect of the latter. Remodeling of other vital organs, such as brain and kidney, also takes place. Therefore, it will be more accurate if we discuss about hypertensive remodeling involving the heart, the brain, and the kidneys, rather than isolated cardiac remodeling. This supports the idea of their simultaneous assessment to identify the early, silent lesions of total hypertensive remodeling. In this context, magnetic resonance imaging is the ideal modality to provide useful information about these organs in a noninvasive fashion and without radiation. For this purpose, we propose a combined protocol to employ MRI in the simultaneous assessment of the heart, brain and kidneys. This protocol should include all necessary indices for the evaluation of hypertensive remodeling in these 3 organs, and could be performed within a reasonable time, not exceeding one hour, so that it remains patient-friendly. Furthermore, a combined protocol may offer all in one examination and save time. Finally, the amount of contrast agent used will be limited granted that post-contrast evaluations of the three organs will be performed after 1 injection. © 2022 BMJ Publishing Group. All rights reserved

The clinical significance of adrenal incidentalomas.

BACKGROUND: The term adrenal incidentaloma (AI) indicates an adrenal mass lesion &gt; 1 cm in diameter discovered during testing for conditions unrelated to adrenal disease. The overall prevalence of these lesions ranges between 3% and 10%. Their incidence increases with age, and it is clinically important to identify AI associated with hormonal activity and/or malignant potential. DESIGN: A detailed Medline search of all English language articles related to AI was carried out, and the clinical implications related to their hormonal activity and malignant potential are discussed. RESULTS: The subclinical hypercortisolism observed in a significant percentage of patients with AI is associated with some of the detrimental effects of continuous autonomous cortisol secretion, including a higher prevalence of hypertension, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus and an increased risk for osteoporotic fractures. However, it remains to be proven whether treatment to reverse subtle glucocorticoid excess is beneficial. Clinically silent phaeochromocytomas and primary adrenal cancer are conditions associated with significantly high morbidity and mortality and require urgent treatment, while the prevalence and clinical significance of autonomous mineralocorticoid secretion are less clearly defined. Size and radiological features are the main predictors of malignant potential. CONCLUSIONS: Patients harbouring AI should be evaluated for the possibility of malignancy and/or subclinical hypercortisolism which is associated with cardiovascular risk and bone loss. However, in the absence of prospective controlled studies correlating biochemical activity with end-organ complications, the long-term consequences of AI remain uncertain and their management remains largely pragmatic