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 >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

The clinical significance of adrenal incidentalomas.

BACKGROUND: The term adrenal incidentaloma (AI) indicates an adrenal mass lesion > 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

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

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

Current status and controversies in adrenal incidentalomas

Adrenal incidentalomas (AI) are serendipitously discovered lesions during abdominal imaging studies that need to be investigated for evidence of hormonal hypersecretion and/or malignancy. Because imaging modalities can reliably identify lesions that carry a high risk of malignancy, we focus on the identification of hypersecretory lesions and those with subclinical activity, particularly Cushing syndrome. Because diverse diagnostic tests and cut-offs are employed, the prevalence of hypersecretory AI varies widely, and there is controversy regarding their long-term sequelae. In this article we provide information regarding current radiological means to define the nature of AI, and the most appropriate biochemical tests for delineating hypersecretory states. We also discuss the duration and intensity of AI follow-up as well as the identification of AI that require specific therapeutic intervention. © 2012 Elsevier Ltd

Progress in aldosteronism: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin-angiotensin system accounts for w10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalaemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Moreover, recent evidence has shown that serum aldosterone correlates with increased blood pressure (BP) in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in BP control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an ACTH effect or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in w50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyse the current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension. © 2015 European Society of Endocrinology

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Impact and duration effect of telemonitoring on HbA1c, BMI and cost in insulin-treated diabetes mellitus patients with inadequate glycemic control: A randomized controlled study

OBJECTIVE: To monitor and control the blood glucose levels in inefficiently insulin-treated patients with type 1 and 2 diabetes mellitus (DM) using a telemonitoring system and determine whether the improvement of HbA1c has a lasting effect following its discontinuation. DESIGN: Seventy inefficiently controlled insulin-treated DM patients using telemonitoring (telemonitoring group-TG) [HbA1c 9.9±2.3% (85±24.9mmol/mol)] and 35 age-, body mass index (BMI)- and Hba1c-matched insulin-treated patients receiving outpatient care (control group-CG) [HbA1c 9.7±2.1% (82±23.4mmol/mol)] were enrolled. Data of TG were transmitted from the glucose-meters to our computers via modem. Communication was achieved via e-mails and mobile phone text-messages through integrated software. HbA1c and BMI were evaluated at enrollment, 3 and 6 months, and 6 months after telemonitoring discontinuation. Frequency of hypo- and hyperglycemias and cost were also analyzed. RESULTS: Significant reduction in HbA1c was observed in TG both at 3 [7.1±1.0% (54±10.5mmol/mol) p<0.001] and 6 months [6.9±0.9% (52±9.5mmol/mol) p<0.001], compared to the CG group at the same timepoints. Significant reduction was also observed in the TG subgroups with HbA1c≥10% and 10>HbA1c≥7.5% at 3 and 6 months, compared to CG. No statistically significant differences in BMI were observed between TG and CG. Six months after telemonitoring discontinuation, HbA1c in TG was slightly increased [7.3±1.0% (56±10.4mol/mol)]. Attenuation was also observed in both TG subgroups. Compared to CG, the number of monthly hypo- and hyperglycemias was reduced in TG. The intervention had a financial benefit for patients living more than 100 km from the health care provider. CONCLUSIONS: Telemonitoring can result in reduction of HbA1c and frequency of hypo- and hyperglycemias. This beneficial effect is slightly attenuated 6 months after terminating telemonitoring. © 2015, Hellenic Endocrine Society. All Right reserved

Vitamin D and aspects of female fertility

The role of vitamin D in female reproduction has been intensively examined over the last few decades. A large body of evidence suggests that vitamin D might have beneficial effects on metabolic/hormonal parameters of PCOS and endometriosis, while it appears to be associated with IVF outcomes. However, due to the heterogeneity among observational and interventional studies, no cause-effect relationship has yet been established. The aim of this review is to analyze recent in vitro animal and human studies which examined the association of vitamin D with disease entities affecting female fertility potential. Recent research data strongly imply that vitamin D is implicated in female reproduction and might represent a beneficial and inexpensive therapeutic approach, in combination with first-line medical treatments, to female infertility. © 2017, Hellenic Endocrine Society. All rights reserved