Normotensive primary aldosteronism

A very unusual case of normotensive primary aldosteronism is described. A 25 year old woman first noticed numbness of both hands followed by a typical tetany attack. The blood pressure was within normal ranges. The results of other physical examinations were negative except for the findings of Trousseau's sign. Hypokalemia, increased potassium clearance, disturbed urine concentration and increased circulating plasma volume were noticeable. Diagnosis was established by (1) increased levels of plasma aldosterone, (2) low plasma renin activity, (3) normal adrenocortical function and (4) typical aldosterone-producing adenoma. After removal of the adenoma, the abnormalities subsided.The lack of hypertension in primary aldosteronism is a rare condition. Several possible causes of normotension must be considered, such as the early phase of primary aldosteronism, essential hypotension associated with primary aldosteronism and lack of concomitant secretion of other mineralocorticoids from the adenoma, but these were all negligible. As blood pressure response to the administration of angiotensin II was lower than is typical for primary aldosteronism, and the patient transiently suffered from frequent attacks of blackouts soon after the operation, the cause of normotension was thought to be due to the existence of a hypotensive mechanism which counteracts the increase in blood pressure in primary aldosteronism.     

Asymptomatic normotensive primary aldosteronism. Case report

We report a case of primary aldosteronism in a 30-year-old woman without hypertension or any other characteristic symptoms. The condition was first suspected by hypokalemia (2.6 mEq/liter), which was incidentally found by routine checkup. There was evidence of suppressed plasma renin activity (PRA) and elevated plasma aldosterone levels. However, the blood pressure never reached a hypertensive level, and the circulating blood volume was within a normal range. A functioning right adrenal tumor was diagnosed by adrenal scintigraphy, computerized x-ray tomography, and adrenal venography. Adrenal venous catheterization suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected, yet the blood pressure remained much the same. Hypertension is not necessarily a sign of primary aldosteronism.     

原发性醛固酮增多症的发病机制

原发性醛固酮增多症是继发性高血压最常见的原因之一,与具有相同危险程度的原发性高血压患者比较,原发性醛固酮增多症患者心、脑血管及肾脏等靶器官的损伤更为多见.近年来,随着对原发性醛固酮增多症的深入研究,发现其发病机制涉及融合基因的产生、醛固酮合成酶(CYP11β2)基因多态性的改变、肾上腺异位受体的表达及7p21-22基因...     

Treatment of primary aldosteronism

The prevalence of primary hyperaldosteronism approaches 10% of?all hypertensive patients, and besides efficient diagnostic procedures, effective treatment is of increasing importance to reverse increased morbidity and mortality. Aldosterone-producing adenoma and unilateral adrenal hyperplasia are amenable to cure?by endoscopic adrenalectomy. Bilateral adrenal hyperplasia (micro- or macronodular), which comprises two-thirds of primary hyperaldosteronism, is treated primarily by mineralocorticoid receptor antagonists (starting dose 12.5-25mg/day spironolactone with titration up to 100mg/day, alternatively 50-100mg/day eplerenone). If blood pressure is not normalised by this first-line treatment, additional treatment with potassium-sparing diuretics (amiloride or triamterene) or calcium channel antagonists is necessary. The start of medication should be closely monitored by serum electrolyte and creatinine controls.     

Genetics of primary aldosteronism

Over the last few years, much progress has been made in understanding the genetic basis of primary aldosteronism. This has led to the diagnosis of the familial forms and has aided the understanding of the basis of sporadic forms of the disease. Such information can be exploited to improve the therapeutic approaches used not only for patients with primary aldosteronism, but also with other forms of hypertension. Here, we review the genetic and the phenotypic features of the familial forms, the genetic variants that influence the sporadic forms and the structure and regulation of the CYP11B1 and CYP11B2 genes.     

Screening for primary aldosteronism

A serum potassium determination is usually recommended for new hypertensive patients as a screening test for primary aldosteronism and as a baseline for drug therapy. Since hypokalemia is not specific for aldosteronism, the authors assessed its use and limitations as a screening test in nine reported studies of 303 patients with aldosterone-producing adenomas (n=252) or adrenal hyperplasia (n=51). The optimal potassium cutoff level and the predictive ability of hypokalemia to detect aldosteronism were analyzed in a primary care setting with different diseases, test characteristics, and prevalences. Optimal screening for primary aldosteronism occurred at serum potassium <3.2 mEq/l in a primary care, low-prevalence population, and at higher potassium levels in higher-prevalence populations. Other screening tests, such as urinary aldoster-one levels and plasma renin activity, showed lower individual test performance characteristics, but when combined were similar in performance to serum potassium measurement. Received from the General Internal Medicine Division, Department of Medicine, Wright State University School of Medicine, Miami Valley Hospital, and Veteran’s Administration Medical Center, Dayton, Ohio. Dr. Snyder is presently a fellow in the Endocrinology Division, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. Presented in part at the Seventh Annual Meeting of the Society for Research and Education in Primary Care Internal Medicine, Microcomputer Users Group, Washington, D.C., May 3, 1984.     

Screening for primary aldosteronism

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.     

Genetic alterations in patients with primary aldosteronism.

The syndrome of primary aldosteronism is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. The most common clinical subtypes of primary aldosteronism are aldosterone-producing adrenocortical adenoma (APA) and bilateral adrenal cortical hyperplasia (idiopathic hyperaldosteronism, or IHA). It has been reported that renin suppression and aldosterone levels are lower and hypokalemia milder in patients with IHA than in patients with APA. In the present study, we investigated the genetic analysis of aldosterone synthase gene, CYP11B2 in patients with primary aldosteronism and review the recent studies. The chimeric CYP11B1/CYP11B2 gene, which is a candidate gene for glucocorticoid-remediable hyperaldosteronism, was not found in either the DNA from aldosteronoma or in the genomic DNA from patients with APA or IHA. Mutations in the CYP21 or CYP11B1 gene were not present in patients with APA. No mutations in the coding region of the CYP11B2 gene were found in patients with IHA or APA. The level of CYP11B2 messenger RNA (mRNA) was much higher in the aldosteronoma portion than in nonadenomatous portion. The overexpression of CYP11B2 mRNA seen in the mononuclear leukocytes of patients with IHA suggests that unidentified aldosterone-stimulating factors or abnormalities of the CYP11B2 promoter region may cause the overproduction of aldosterone characteristic of IHA. The variants of the CYP11B2 gene may also contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.     

Diagnosis of primary aldosteronism: from screening to subtype differentiation.

Numerous studies conducted in recent years have reported an increase in the prevalence of primary aldosteronism (PA). This increase has arisen because of changes in our screening methods used to detect PA, notably the widespread use of the ratio of plasma aldosterone concentration to plasma renin activity. A positive screening result, however, is not diagnostic and requires a confirmatory test. Strategies for screening and confirmation of PA and the techniques to identify the two main subtypes of PA--aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH)--are particularly important because hypertension in APA can be cured by adrenalectomy, whereas individuals affected with BAH can receive targeted medical treatment with mineralocorticoid receptor antagonists.     

原发性醛固酮增多症的诊断与治疗

原发性醛固酮增多症(原醛症)是继发性高血压最常见的病因之一,以往通常只对低血钾的高血压患者进行原醛相关筛查.近期研究表明原醛症患者中仅25％可见低血钾表现,目前新发高血压患者中原醛症患者的发生率可达10％ ～ 15％.本文就原醛症的诊断与治疗做一综述.     

原发性醛固酮增多症的诊断与治疗

原发性醛固酮增多症(primary aldosteronism,PA)是一组由于醛固酮不恰当的高分泌,部分是由于肾素-血管紧张素系统(renin-angiotensin system,RAS)的自主性分泌而引起的疾病。过多的醛固酮导致高血压、心血管损害、肾素抑制、     

Diagnosis and treatment of primary aldosteronism

Primary aldosteronism involves more than 11% of hypertensive patients who are referred to specialized centers for the diagnosis and treatment of hypertension. If not diagnosed early it causes an excess damage to the heart, vessels and kidney, which translates into an cardiovascular events. Since these ominous consequences can be corrected with a timely diagnosis and an appropriate therapy, physicians should exercise a high degree of alert concerning the possibility that primary aldosteronism is present in hypertensive patients. The purpose of this review is to provide up-dated information on the strategy for case detection, the subtype differentiation and the management of primary aldosteronism.     

Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism

The clinical presentations of the patient with pheochromocytoma—a rare endocrine neoplasm—include adrenal incidentaloma, hypertensive paroxysms, sustained apparent polygenic hypertension, hypertension in pregnancy, and hypertensive crisis induced by anesthesia. Although when undiagnosed a pheochromocytoma can be lethal, it can usually be cured with surgery. Biochemical documentation with measurements of fractionated metanephrines and catecholamines should precede imaging studies. Abdomen and pelvis computed imaging is usually the first imaging test. Careful preoperative pharmacologic preparation is important for a successful surgical outcome. Adrenal pheochromocytomas can usually be removed laparoscopically, whereas, catecholamine-secreting paragangliomas typically require an open approach. All first degree relatives of pheochromocytoma patients should have biochemical testing. In addition, molecular genetic testing for germline mutations should be considered in most patients with adrenal pheochromocytoma and in all patients with paraganglioma. Primary aldosteronism is a relatively common form of secondary hypertension—affecting 5 to 10% of all patients with hypertension. A plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio should be obtained in patients with hypertension and hypokalemia, resistant hypertension, adrenal incidentaloma and hypertension, onset of hypertension at a young age (e.g., < 20 years of age), severe hypertension (e.g., ≥160 mm Hg systolic or ≥100 mm Hg diastolic), or whenever the clinician is considering other forms of secondary hypertension. The PAC/PRA ratio is a case finding test and a positive result should be confirmed with aldosterone suppression testing with either oral or intravenous sodium loading. The treatment goals for patients with primary aldosteronism are to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage. Both the subtype of primary aldosteronism and patient preference should dictate the treatment approach.