ABSTRACT
Primary aldosteronism is the most common form of secondary hypertension and patients with hyperaldosteronism are more prone to premature cardiovascular complications compared to essential hypertensives. The diagnostic flow-chart for the diagnosis of PA is performed in three steps: a) screening; b) confirmation; and c) subtype differentiation. Instead of proceeding directly to subtype classification, the recently published Endocrine Society Guidelines recommend that patients with a positive ARR should undergo a confirmatory test, in order to definitively confirm or exclude the diagnosis of PA. The Guidelines recognize four testing procedures: oral sodium loading, saline infusion, fludrocortisone suppression, and captopril challenge. Herein we discuss the diagnostic protocols for these confirmatory tests and highlight both the advantages and contraindications and we discuss studies in which these confirmatory tests have been compared.
Subject(s)
Diagnostic Techniques, Endocrine , Hyperaldosteronism/diagnosis , Validation Studies as Topic , Aldosterone/analysis , Algorithms , Diagnostic Techniques, Endocrine/standards , Fludrocortisone , Humans , Renin/analysis , Sodium, DietaryABSTRACT
BACKGROUND: Endothelin-1 (ET-1) may function as an aldosterone secretagogue and, in turn, aldosterone can upregulate ET-1 expression. Hence, the existence of a feedforward loop involving ETs and aldosterone has been speculated in primary aldosteronism (PA). In the present study, we sought to examine ET-1 secretion from the adrenal glands in patients with PA. DESIGN: We determined ET-1 levels in blood samples obtained during adrenal venous sampling of patients affected by PA (n=17). Furthermore, we examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n=9) and control normal adrenals (n=3). METHODS: Blood ET-1 levels were determined by RIA. Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays. RESULTS: ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Moreover, cortisol-normalized ET-1 levels did not show lateralized adrenal ET-1 secretion in APAs. Through gene expression profiling with microarray performed in a distinct set of APA individuals (n=9), we confirmed the adrenal expression of a complete ET system, but we did not detect a significant upregulation of ET components within the APA tissue compared with normal adrenals. CONCLUSIONS: The present data argue against the hypothesis of increased ET-1 secretion from APAs and do not support a general role for adrenal ET-1 in the vascular pathophysiology of PA.
Subject(s)
Adrenal Glands/metabolism , Aldosterone/metabolism , Endothelin-1/blood , Hyperaldosteronism/metabolism , Adenoma/metabolism , Adenoma/physiopathology , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/physiopathology , Aged , Aldosterone/blood , Aspartic Acid Endopeptidases/genetics , Endothelin-1/genetics , Endothelin-Converting Enzymes , Female , Humans , Hyperaldosteronism/physiopathology , Male , Metalloendopeptidases/genetics , Middle Aged , RNA, Messenger/metabolism , Receptor, Endothelin A/genetics , Receptor, Endothelin B/geneticsABSTRACT
Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.
Subject(s)
Cognition/physiology , Hypotension/physiopathology , Hypotension/psychology , Blood Pressure/physiology , Brain/blood supply , Cognition Disorders/epidemiology , Cognition Disorders/physiopathology , Dementia/epidemiology , Dementia/physiopathology , Humans , Regional Blood Flow/physiologyABSTRACT
The purpose of this review is to summarize the current knowledge regarding metabolic syndrome prevalence and features in primary aldosteronism. We will also discuss the link between aldosterone and the different metabolic changes typical of the metabolic syndrome. Hypertensive patients have a high prevalence of obesity, dyslipidemia and hyperglycaemia. These are risk factors for the metabolic syndrome, and are associated with an increased cardiovascular risk profile. In particular, insulin resistance seems to be the major alteration in patients affected by primary aldosteronism. We will then describe the experimental and clinical evidences of the role of aldosterone in the pathogenesis of insulin resistance. Higher rates of cardiovascular events have been recently reported in primary aldosteronism: they could be partly due to the increased prevalence of the metabolic syndrome in this disorder.
Subject(s)
Aldosterone/physiology , Metabolic Syndrome/etiology , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/etiology , Hyperaldosteronism/metabolism , Insulin Resistance , Metabolic Syndrome/metabolism , Obesity/complications , Obesity/metabolismABSTRACT
The chemotherapeutic effects of different doses of adriamycin in (C3H x 020)F1 mice bearing mammary carcinoma have been investigated and a model of the growth of neoplastic cells under the influence of treatment is described. An estimate of cell kill and of the fraction of cells surviving after treatment is given by the efficacy constant K, which is a function of the dose level of the drug. The therapeutic value of each treatment is, however, also related to the degree of toxicity which in our model is expressed by the probability of death for each dose level.