Vitamins and Hormones最新文献

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is increasingly recognized as a spectrum disorder, ranging from subclinical to overt forms. Clinical manifestations include hypertension, often resistant, and may be accompanied by hypokalemia. Beyond BP elevation, PA is associated with a disproportionately high risk of cardiovascular and metabolic complications compared to essential hypertension, including coronary artery disease, arrhythmias, heart failure, left ventricular hypertrophy, stroke, metabolic syndrome and impaired glucose metabolism. The negative effects of aldosterone excess induce greater target organ damage than seen in primary hypertension, including arterial stiffness, cardiac remodeling, and renal dysfunction. Targeted treatments such as mineralocorticoid receptor (MR) antagonists and adrenalectomy have demonstrated efficacy in reducing these risks and improving patient outcomes. Therefore, early detection and management of PA are essential for preventing long-term cardiovascular and metabolic complications.

Mild autonomous cortisol co-secretion (MACS) in primary aldosteronism (PA)-referred to as Connshing syndrome, C-PA, or MACS-PA-has emerged as a clinically significant adrenal disorder that substantially influences the prognosis and management of PA. In this chapter, a comprehensive overview of current knowledge and recent advances in the pathophysiology, diagnosis, and clinical impact of Connshing syndrome is presented, highlighting its importance for personalized treatment strategies and improved patient outcomes.

Primary aldosteronism (PA) is the leading cause of secondary hypertension. In general, two principal subtypes are distinguished: A lateralized form in which aldosterone hypersecretion originates from a single adrenal gland, and a non-lateralized form characterized by bilateral adrenal involvement. In patients with lateralized PA, adrenalectomy yields more favorable clinical and biochemical outcomes than pharmacological therapy. Accurate subtype classification is therefore essential to guide the optimal treatment. Adrenal venous sampling (AVS) remains the gold standard for localizing aldosterone excess, though its technical difficulty and limited availability pose challenges. In addition, molecular imaging has emerged as a promising non-invasive alternative in recent years, with novel PET tracers showing potential to complement or replace AVS in selected patients. This chapter summarizes the indications, technical aspects, and interpretation of AVS, and reviews current molecular imaging approaches, emphasizing their potential role as complementary tools in the diagnostic work-up of PA.

The Renin-Angiotensin-Aldosterone System (RAAS) is a cornerstone of cardiovascular and electrolyte homeostasis, and its dysregulation is central to the pathophysiology of hypertension, heart failure, and chronic kidney disease. This chapter provides a comprehensive overview of the RAAS, from its classical and alternative signaling pathways to its clinical implications. We delve into the pathological consequences of both RAAS overactivation and its suppression. A significant focus is placed on the biochemical evaluation of the RAAS, tracing the chronological progression from early bioassays to modern automated immunoassays and high-resolution mass spectrometry for measuring renin and aldosterone. We critically examine the methodologies for determining plasma renin activity (PRA) and direct renin Concentration (DRC), and the nuances of plasma and urinary aldosterone quantification. The aldosterone-to-renin ratio (ARR) is highlighted as the essential screening tool for PA, with a detailed discussion of assay-specific cut-offs and the imperative of laboratory-specific validation. Furthermore, the chapter outlines the numerous preanalytical and analytical variables that profoundly influence RAAS component measurements, including patient posture, diet, and the significant confounding effects of various medications. Adherence to standardized protocols for sample collection, handling, and analysis is emphasized as critical for accurate diagnosis and management.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension, characterized by autonomous aldosterone production, unregulated by sodium balance or renin-angiotensin system activity. Once considered a rare, PA is now recognized as a spectrum that includes subclinical forms in normotensive individuals. Aldosterone synthesis, normally regulated by angiotensin II, extracellular potassium, and adrenocorticotropic hormone (ACTH), undergoes dysregulated in PA, often due to somatic or germline mutations affecting ion channels or intracellular signaling pathways. This disruption promotes morphological alteration in the adrenal cortex, including aldosterone-producing cell clusters (APCCs), micronodules, and aldosterone-producing adenomas (APAs). These lesions contribute to renin-independent aldosterone secretion and inappropriate ACTH sensitivity. Aldosterone acts through the mineralocorticoid receptor (MR), triggering both genomic and non-genomic effects. MR activation in multiple tissues promotes cardiovascular and metabolic damage, often independent of blood pressure. These insights support early detection and a broader clinical approach to PA, incorporating its genetic, structural, and molecular basis.

Low-renin hypertension (LRH) affects approximately 30 percent of patients with arterial hypertension and represents a spectrum of heterogeneous disorders characterized by low renin levels, increased sodium reabsorption, and expanded circulating volume. LRH includes monogenic and acquired secondary forms; however, the majority of the patients-particularly older individuals and those of African descent-present essential hypertension. Primary aldosteronism is the most frequent secondary cause, marked by excessive and autonomous aldosterone secretion. Other monogenic forms, such as Liddle syndrome, apparent mineralocorticoid excess and familial hyperkalaemic hypertension, are distinguished by specific biochemical and genetic profiles. Acquired causes of LRH include high dietary sodium intake, renal diseases, drugs inhibiting the renin-angiotensin-aldosterone system, and exogenous or endogenous factors like high consumption of mineralocorticoid-like substances (i.e. licorice) or cortisol excess. Careful clinical evaluation, including family history, and measurement of renin, aldosterone, and potassium levels are essential for accurate diagnosis and tailored treatment. Mineralocorticoid receptor activation and/or increased sodium reabsorption are a common mechanism in the pathogenesis of LRH, with a continuum between essential and secondary forms. Recognizing these subtypes has significant therapeutic implications, as targeted treatments can improve long-term outcomes and reduce cardiovascular events. This chapter describes the differential diagnosis and underlying mechanisms of the most common conditions presenting with a LRH phenotype, with a focus on diagnostic and therapeutic approaches.

Introduction: Primary aldosteronism (PA) is a common yet underrecognized cause of secondary hypertension. Once identified as Conn's syndrome with hypokalemia and adrenal tumors, PA now includes broader forms with inappropriate aldosterone secretion and low renin. Despite its link to cardiovascular risk, under 15 percent of eligible patients are screened, leading to underestimated prevalence and missed treatment chances. Main Section: Improved assays and awareness reveal PA is more frequent than believed, often without hypokalemia and even in normotensive patients. Meta-analyses show PA prevalence of 6.8-10 percent in hypertensive groups, rising over 50 percent in resistant hypertension. Diagnostic and population differences cause varied detection, highlighting the need for standard screening. PA rates might increase in patients with higher reno-cardiometabolic compromise. Aldosterone excess promotes cardiovascular remodeling and arrhythmias, so early PA diagnosis in these groups can improve outcomes. Although current guidelines recommend broad screening for PA, particularly in high-risk patients, there is a growing trend toward universal screening in all individuals with hypertension. PA also occurs in mild or normotensive individuals (>10 percent prevalence), so many hypertensives qualify for screening. Adhering to guidelines supports screening nearly all hypertensives for timely diagnosis and treatment.

Conclusions: PA is a common, clinically important yet often missed cause of hypertension, affecting resistant, mild, and normotensive cases. It is prevalent among those patients with cardiovascular complications. Guidelines, though recommending targeted screening, effectively endorse broad testing to enhance detection. Expanding screening and standardizing diagnostics are crucial to optimize diagnosis, enable tailored therapy, reduce cardiovascular risk, and improve outcomes.

Aldosterone, the principal mineralocorticoid, is exclusively synthesized in the glomerular zone of the adrenal cortex. Its primary function is to maintain water and electrolyte balance and regulate blood pressure. The synthesis of aldosterone begins with the transport of cholesterol to the mitochondria, a process that is mediated by the StAR protein. This is followed by a sequence of reactions that are catalyzed by specific enzymes. CYP11A1, 3β-HSD2, CYP21A2, and finally CYP11B2. The regulation of its production is classified as acute, dependent on the rapid activation of StAR, and chronic, involving the sustained transcription of CYP11B2.The regulation of this process is influenced by three physiological stimuli: angiotensin II, which is produced through the renin-angiotensin system, increased extracellular potassium, and ACTH. Angiotensin II and potassium have been shown to activate intracellular signals that increase cytoplasmic calcium, thereby promoting both StAR activation and CYP11B2 expression. ACTH stimulates synthesis via the cAMP/PKA pathway, although its effect is brief.Other modulators of significance include natriuretic peptides, dopamine, serotonin, inflammatory cytokines, microRNAs, and sex hormones such as testosterone and progesterone. Comprehension of these mechanisms is imperative for the effective management of pathologies, including primary hyperaldosteronism, a condition that is associated with secondary hypertension and progressive organ damage.

The diagnosis of primary aldosteronism (PA) requires an Aldosterone-Renin-Ratio (ARR) to demonstrate a low or undetectable renin level and plasma aldosterone concentration that is inappropriately high for salt and volume status. The confirmatory tests are mandatory by the Endocrine Society Guideline for a definitive diagnosis of PA except if the patient presents spontaneous hypokalemia and Plasmatic Aldosterone Concentration (PAC) above 20 ng/dl plus Plasmatic Renin Activity (PRA) or Direct Renin Concentration (DRC) below assay detection limits. Then, the Endocrine Society Guideline recommends at least confirmatory test for confirmation or exclusion of the diagnosis of PA. Thanks to these confirmatory tests, the patients with negative confirmatory tests do not require unnecessarily invasive procedures such as adrenal vein sampling (AVS) or surgery. These tests are based on the premise that in PA the aldosterone secretion is at least partially autonomous from renin and therefore angiotensin release. Currently, there is no enough evidence to recommend one test over the others. The most employed suppression tests are saline infusion (intravenous infusion or orally), fludrocortisone (FST) or a captopril challenge (CCT) test. Several studies have compared the performance of these tests, but there is wide variability between them, the choice of confirmatory test and in threshold values between referral centers, because of differences in laboratory methodologies and patients' characteristics.

Primary aldosteronism (PA) is a prevalent yet underdiagnosed cause of hypertension, significantly contributing to cardiovascular morbidity. Despite established guidelines, the diagnostic pathway for PA remains complex, hindered by analytical and physiological variability in aldosterone and renin measurements, and limitations of the aldosterone-to-renin ratio (ARR) for the screening. These challenges often lead to delayed diagnosis and suboptimal patient outcomes. This chapter critically reviews emerging innovations designed to overcome these barriers, exploring advancements across several domains. We examine novel applications of traditional biomarkers, such as renin suppression and angiotensin II-based ratios, alongside the utility of non-invasive salivary as well as urinary aldosterone measurements. Furthermore, the integration of steroidomics, proteomics, and molecular profiling, including microRNAs and extracellular vesicles, is discussed to offer deeper biochemical insights. Finally, transformative potential of functional imaging techniques, particularly CXCR4-targeted PET, and the increasing role of machine learning in refining diagnostic algorithms and identifying novel biomarkers is explored. These advancements in novel biomarkers and work-up strategies promise to enhance the sensitivity, specificity, and practicality of PA diagnosis, facilitating earlier intervention and improving patient care.