Robustness of steroidomics-based machine learning for diagnosis of primary aldosteronism: a laboratory medicine perspective.

Objectives: Use of machine learning (ML) in diagnostics offers promise to optimise interpretation of laboratory data and guide clinical decision-making. For this, ML-based outputs should provide robustly reproducible results at least as good as the underlying laboratory data. The objective of this study was to assess robustness of ML-based steroid-probability-scores for diagnosis of primary aldosteronism (PA).

The saline infusion test with mass spectrometric measurements of aldosterone to confirm primary aldosteronism.

Objective: Confirmation of primary aldosteronism with the saline infusion test requires accurate measurements of plasma aldosterone, which is best achieved by mass spectrometry. Diagnostic performance, appropriate cut-offs and intra-patient variability of the test remain inadequately defined. The objective of this prospective multicenter cohort study was to address these limitations.

Long-Term Persistence of Glycemic Dysregulation in Patients With a History of Pheochromocytoma/Paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism.

Background: Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

Background: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR).

Methods: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate).

Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism.

Context: Clinical practice guidelines recommend the lateralization index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA).

Objective: Our goal was to identify the optimal LI cutoffs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure.

Methods: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1550 patients with PA who underwent AVS, with and/or without adrenocorticotropin (ACTH) stimulation.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

Background: Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA).

Methods: Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others.

Unawareness of Primary Aldosteronism as a Common Cause of Hypokalemia - Insights from the IPAHK+ Trial (Incidence of Primary Aldosteronism in Patients with Hypokalemia).

Hypokalemia plays an important role in the diagnosis and management of primary aldosteronism (PA). While the hypokalemic variant of the disease accounts for about one third of all cases, little is known about the incidence of PA in hypokalemic populations. The IPAHK+ study is an epidemiological, cross-sectional trial to provide evidence on the incidence of PA in hypokalemic patients from a university hospital outpatient population.

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.

Preanalytical Considerations and Outpatient Versus Inpatient Tests of Plasma Metanephrines to Diagnose Pheochromocytoma.

Context: Sampling of blood in the supine position for diagnosis of pheochromocytoma and paraganglioma (PPGL) results in lower rates of false positives for plasma normetanephrine than seated sampling. It is unclear how inpatient vs outpatient testing and other preanalytical factors impact false positives.

Objective: We aimed to identify preanalytical precautions to minimize false-positive results for plasma metanephrines.

The Saline Infusion Test for Primary Aldosteronism: Implications of Immunoassay Inaccuracy.

Context: Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results.

Objective: This study aimed to establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA.

Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics.

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHKstudy is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population.

Hypokalemia and the Prevalence of Primary Aldosteronism.

Hypokalemia is closely linked with the pathophysiology of primary aldosteronism (PA). Although hypokalemic PA is less common than the normokalemic course of the disease, hypokalemia is of particular importance for the manifestation and development of comorbidities. Specifically, a growing body of evidence demonstrates that hypokalemia in PA patients is associated with a more severe disease course regarding cardiovascular and metabolic morbidity and mortality.

Lack of the pH-sensing Receptor TDAG8 [GPR65] in Macrophages Plays a Detrimental Role in Murine Models of Inflammatory Bowel Disease.

Background: Tissue inflammation in inflammatory bowel diseases [IBD] is associated with local acidification. Genetic variants in the pH-sensing G protein-coupled receptor 65, also known as T cell death-associated gene 8 [TDAG8], have been implicated in IBD and other autoimmune diseases. Since the role of TDAG8 in intestinal inflammation remains unclear, we investigated the function of TDAG8 using murine colitis models.

The Proton-activated Receptor GPR4 Modulates Intestinal Inflammation.

Background And Aims: During active inflammation, intraluminal intestinal pH is decreased in patients with inflammatory bowel disease [IBD]. Acidic pH may play a role in IBD pathophysiology. Recently, proton-sensing G-protein coupled receptors were identified, including GPR4, OGR1 [GPR68], and TDAG8 [GPR65].

Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract?

Background: In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease.

Method: Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group).