Primary Aldosteronism: State-of-the-Art Review.

We are witnessing a revolution in our understanding of primary aldosteronism (PA). In the past 2 decades, we have learned that PA is a highly prevalent syndrome that is largely attributable to pathogenic somatic mutations, that contributes to cardiovascular, metabolic, and kidney disease, and that when recognized, can be adequately treated with widely available mineralocorticoid receptor antagonists and/or surgical adrenalectomy. Unfortunately, PA is rarely diagnosed, or adequately treated, mainly because of a lack of awareness and education.

Cardiac Structure and Function Across the Spectrum of Aldosteronism: the Atherosclerosis Risk in Communities Study.

Background: Aldosterone production and mineralocorticoid receptor activation are implicated in myocardial fibrosis and cardiovascular events.

Methods: Cardiac structure and function were assessed in 4547 participants without prevalent heart failure (HF) in the ARIC study (Atherosclerosis Risk in Communities), with echocardiography, aldosterone, and plasma renin activity measurement (2011-2013). Subjects were characterized by plasma renin activity as suppressed (≤0.

Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions.

Context: Clinicians frequently rely on aldosterone thresholds derived from older immunoassays to diagnose primary aldosteronism. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly widespread and reported to yield lower aldosterone concentrations.

Objective: Given the health impact of incorrect interpretations of aldosterone levels, we compared measurements using LC-MS/MS and immunoassay across the full range of aldosterone physiology by evaluating distinct regulation by angiotensin II and adrenocorticotropin (ACTH).

Quality of Life and its Determinants in Patients With Adrenal Insufficiency: A Survey Study at 3 Centers in the United States.

Context: Current evidence on determinants of quality of life (QoL) in patients with adrenal insufficiency (AI) is limited.

Objective: This work aimed to identify the determinants of QoL in different subtypes of AI.

Methods: This multicenter cross-sectional survey study was conducted using a patient-centered questionnaire, the Short Form-36.

Discriminative Capacity of CT Volumetry to Identify Autonomous Cortisol Secretion in Incidental Adrenal Adenomas.

Context: Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas, given the association with increased cardiometabolic disease.

Objective: To evaluate the discriminatory capacity of 3-dimensional volumetry on computed tomography (CT) to identify ACS.

Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism.

Background: Normal-appearing adrenal glands on cross-sectional imaging may still be the source of aldosterone production in primary aldosteronism (PA).

Methods: We evaluated the prevalence of aldosterone production among morphologically normal-appearing adrenal glands and the impact of this phenomenon on interpretations of localization studies and treatment decisions. We performed a retrospective cohort study of PA patients with at least 1 normal adrenal gland and reanalyzed contemporary studies to assess interpretations of imaging and adrenal venous sampling (AVS) at the individual patient and adrenal levels.

Screening Rates for Primary Aldosteronism Among Individuals With Hypertension Plus Hypokalemia: A Population-Based Retrospective Cohort Study.

Primary aldosteronism is a common, yet highly underdiagnosed, cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Hypertension plus hypokalemia is a guideline-recommended indication to screen for primary aldosteronism, yet the uptake of this recommendation at the population level remains unknown. We performed a population-based retrospective cohort study of adults ≥18 years old in Ontario, Canada, with hypertension plus hypokalemia (potassium <3.

Glucocorticoids for therapeutic immunosuppression: Clinical pearls for the practicing neurologist.

Given widespread use of glucocorticoid therapy in neurologic disease, understanding glucocorticoid pharmacology and risk is paramount for the practicing neurologist. While dosing and tapering regimens vary depending on the neurological disease and indication being treated, there are important general principles of glucocorticoid prescribing and monitoring that can guide clinical decision-making. Glucocorticoid-related toxicities can occur across multiple organ systems, including hypertension; dyslipidemia; weight gain; hyperglycemia; osteoporosis and avascular necrosis; myopathy; gastrointestinal bleeding; infection; and neuropsychiatric effects with sleep, mood disturbance and cognition.

The Impact of the COVID-19 Pandemic on Self-Reported Outcomes in Patients With Adrenal Insufficiency.

Context: The COVID-19 pandemic has impacted healthcare environment.

Objective: To determine the impact of the pandemic on self-reported outcomes in patients with adrenal insufficiency (AI).

Design And Setting: Prospective longitudinal survey study at 2 tertiary centers.

Adrenocorticotropic Hormone-Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies.

[Figure: see text].

American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach.

Objective: The aim of this Disease State Clinical Review is to provide a practical approach to patients with newly diagnosed adrenocortical carcinoma, as well as to follow-up and management of patients with persistent or recurrent disease.

Methods: This is a case-based clinical review. The provided recommendations are based on evidence available from randomized prospective clinical studies, cohort studies, cross-sectional and case-based studies, and expert opinions.

Assessment of mild autonomous cortisol secretion among incidentally discovered adrenal masses.

Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. Therefore, it is advised that all patients with an incidentally discovered adrenal mass be tested for MACS.

Intraindividual Variability of Aldosterone Concentrations in Primary Aldosteronism: Implications for Case Detection.

Primary aldosteronism is an underdiagnosed cause of hypertension. Although inadequate screening is one reason for underdiagnosis, another important contributor is that clinicians may inappropriately exclude the diagnosis when screening aldosterone concentrations fall below traditionally established thresholds. We evaluated the intraindividual variability in screening aldosterone concentrations and aldosterone-to-renin ratios, and how this variability could impact case detection, among 51 patients with confirmed primary aldosteronism who had 2 or more screening measurements of renin and aldosterone on different days.

Variability of Aldosterone Measurements During Adrenal Venous Sampling for Primary Aldosteronism.

Background: Variability of aldosterone concentrations has been described in patients with primary aldosteronism.

Methods: We performed a retrospective cohort study of 340 patients with primary aldosteronism who underwent adrenal venous sampling (AVS) at a tertiary referral center, 116 of whom also had a peripheral venous aldosterone measured hours before the procedure. AVS was performed by the same interventional radiologist using bilateral, simultaneous sampling, under unstimulated and then stimulated conditions, and each sample was obtained in triplicate.

MANAGEMENT OF ENDOCRINE DISEASE: The role of surgical adrenalectomy in primary aldosteronism.

Primary aldosteronism is common and contributes to adverse cardiovascular, kidney, and metabolic outcomes. When instituted early and effectively, targeted therapies can mitigate these adverse outcomes. Surgical adrenalectomy is among the most effective treatments because it has the potential to cure, or attenuate the severity of, pathologic aldosterone excess, resulting in a host of biochemical and clinical changes that improve health outcomes.

Determinants of Self-reported Health Outcomes in Adrenal Insufficiency: A Multisite Survey Study.

Context: Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes.

Objective: To determine predictors of adverse outcomes in different subtypes of AI.

Design And Setting: Cross-sectional survey study at 2 tertiary centers.

Evolution of the Primary Aldosteronism Syndrome: Updating the Approach.

Context: New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that primary aldosteronism is a prevalent syndrome that is mostly unrecognized, and present a pragmatic and pathophysiology-based approach to improve diagnosis and treatment.

Methods: Evidence was gathered from published guidelines and studies identified from PubMed by searching for primary aldosteronism, aldosterone, renin, and hypertension.

The Prevalence of Primary Aldosteronism and Evolving Approaches for Treatment.

Over six decades since primary aldosteronism was first described, much has been learned about its prevalence and optimal treatment. Estimates of the prevalence of primary aldosteronism have increased considerably over the years, even exceeding 20% in some populations of resistant hypertension. Even in patients with normal blood pressures, the prevalence of overt primary aldosteronism and dysregulated aldosterone production may be more common than appreciated.

Primary aldosteronism.

Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identify patients who might benefit from effective and targeted treatment modalities.

Treatment of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. ACC is capable of secreting excess adrenocortical hormones, which can compound morbidity and compromise clinical outcomes. By the time most ACCs are diagnosed, there is usually locoregional or metastatic disease.

Primary Aldosteronism Diagnosis and Management: A Clinical Approach.

Primary aldosteronism used to be considered a rare cause of secondary hypertension. However, accruing evidence indicates that primary aldosteronism is more common than previously recognized. The implications of this increased prevalence are important to public health because autonomous aldosterone production contributes to cardiovascular disease and can be treated in a targeted manner.

Primary adrenal insufficiency in the United States: diagnostic error and patient satisfaction with treatment.

Background The objective of the study was to assess the diagnostic process, access to care and treatment adequacy for primary adrenal insufficiency (PAI) patients from a US-based online registry. Methods The National Adrenal Diseases Foundation (NADF) patient registry from 2015 to 2016 was used for a cross-sectional assessment of PAI patients. Five hundred and forty-one adults met the study inclusion criteria (US residents, age >20, self-reported physician diagnosis of PAI and replacement dosing for cortisol).

Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population.