Elevated Serum Aldosterone Levels Research Articles

Aldosterone-Regulated Sodium Transport and Blood Pressure.

Aldosterone is a major mineralocorticoid steroid hormone secreted by glomerulosa cells in the adrenal cortex. It regulates a variety of physiological responses including those to oxidative stress, inflammation, fluid disruption, and abnormal blood pressure through its actions on various tissues including the kidney, heart, and the central nervous system. Aldosterone synthesis is primarily regulated by angiotensin II, K+ concentration, and adrenocorticotrophic hormone. Elevated serum aldosterone levels increase blood pressure largely by increasing Na+ re-absorption in the kidney through regulating transcription and activity of the epithelial sodium channel (ENaC). This review focuses on the signaling pathways involved in aldosterone synthesis and its effects on Na+ reabsorption through ENaC.

Renin-aldosterone system evaluation over four decades in an extended family with autosomal dominant pseudohypoaldosteronism due to a deletion in the NR3C2 gene

Renal pseudohypoaldosteronism (PHA1) is a mild form of an aldosterone-resistance syndrome caused by mutations in the NR3C2 gene that codes for the mineralocorticoid receptor (MR). The disease is inherited as an autosomal dominant trait characterized by signs and symptoms of salt-losing in infancy. Disease manifestations could be severe in infancy but improve after the age of 1–3 years. Some affected members are asymptomatic and remain so life-long. In this study, we report the identification of a large deletion in the NR3C2 gene (c.1897+1_1898−1)_(c.*2955+?)del in renal PHA1 patients from an extended family spanning four generations. We prospectively evaluated the plasma renin activity and serum aldosterone profiles over four decades in symptomatic and asymptomatic affected family members. The benefits of early diagnosis on the clinical outcome were assessed as well. The long-term follow-up showed an age-dependent decrease in both plasma renin activity and serum aldosterone levels over the years. However, aldosterone levels remain high life-long. Thus, levels of aldosterone are a reliable marker to detect asymptomatic family members. The diagnosis of the proposita led to early diagnosis and therapy in other affected family members, significantly mitigating the clinical course. Despite the extremely elevated serum aldosterone levels during pregnancy, affected pregnant women did not experience any ill effects. However, this should be verified by observations in other adult patients.

Is primary aldosteronism a potential risk factor for aortic dissection? A case report and literature review

BackgroundPrimary aldosteronism (PA) increases the risk of cardiovascular morbidity, including stroke, coronary artery disease, atrial fibrillation, and heart failure. The relationship between primary aldosteronism and aortic dissection has rarely been reported. We report a case of aortic dissection caused by secondary hypertension from PA and review similar cases in the literature.Case presentationA 56-year-old woman with a history of surgery for aortic dissection presented for follow-up of hypertension and a left adrenal mass. She had been diagnosed with hypertension and hypokalemia in 2003. Blood pressure had been controlled by antihypertensive medications. In 2009, she presented with chest and back pain; she was diagnosed with aortic dissection by computed tomography (CT). She underwent placement of an endovascular aortic stent graft. CT at that time showed a left adrenal mass with a diameter of 1 cm. In 2017, CT reexamination revealed that the left adrenal mass had grown to 3 cm in diameter. Laboratory data showed blood potassium 2.4 mmol/L (reference range: 3.5–5.3 mmol/L). The plasma aldosterone/renin ratio was elevated because of suppressed plasma renin and elevated serum aldosterone levels. Plasma aldosterone levels were not suppressed after taking captopril. Positron emission tomography/CT showed that the left adrenal tumor radiographic uptake was slightly increased (maximum standardized uptake value of 2.2), and metastasis was not detected. Laparoscopic adrenalectomy was performed, and an adrenocortical adenoma was confirmed histopathologically. After surgery, blood pressure and laboratory findings were within their reference ranges without any pharmacological treatment.ConclusionsOur patient and the literature suggest that PA is a potential cause of aortic dissection. Diagnosing PA in the early stages of the disease and early treatment are important because affected patients may be at increased risk of aortic dissection.

MON-320 CONN’S SYNDROME MASQUERADING AS NORMOTENSIVE HYPOKALEMIC PARALYSIS, WITH SUBSEQUENT KALIOPENIC NEPHROPATHY

Hypokalemic paralysis even without hypertension, can herald a diagnosis of primary hyperaldosteronism (PHA). This patient presented with hypokalemic paralysis without evidence of hypertension during the initial 2 – 3 years. Following a diagnosis of adrenal carcinoma, he developed features of chronic tubulointerstitial nephritis denoting kaliopenic nephropathy due to prolonged hypokalemia. A 34-year-old male with a history of muscle cramps since 2 – 3 years, presented with flaccid lower limb weakness causing difficulty in walking over 3 days. His s. potassium was 1.6 meq/L. He was normotensive with alkalosis, increased TTKG and normal magnesium levels. Past records didn’t reveal any evidence of anorexia, laxative or diuretic abuse. Initial USS scan didn’t reveal any adrenal masses. Creatinine was normal. A working differential of Gitlemann’s syndrome was made despite normal magnesium levels and urine calcium excretion. He was treated with high dose KCL with prompt recovery of his weakness. His CPK was 9600 mg/dl denoting hypokalemia-induced rhabdomyolysis. During follow up his compliance was poor. After 2 years he presented with hypokalemic paralysis and blood pressure of 170/100mmHg. Investigations revealed elevated serum aldosterone levels >1650 pg/ml; with suppressed serum renin 0.4 ng/L. 24-hr urinary VMA, 9am s. cortisol, thyroid test, dexa.Sup.T., DHEA levels, parathyroid hormone, calcium and phosphate levels were normal. USS scan followed by CECT abdomen on this occasion revealed a left heterogeneous suprarenal mass, measuring 5.8 x 4.8 cm with poor contrast enhancement, favoring an adrenal carcinoma. He underwent open left adrenalectomy, which resolved his hypokalemia. Histological findings were consistent with an adrenal cortical adenoma. Subsequently, creatinine rose to 1.7mg/dl. Renal biopsy revealed primary tubular interstitial nephritis with isometric vacuolations in proximal tubules without evidence of hypertensive nephrosclerosis, conforming a diagnosis of kaliopenic nephropathy. He didn’t attend the clinic for 9 months, and he presented again with leg weakness due to severe hypokalemia. USS scan and CT scan reveled recurrence of adrenal carcinoma with metastases. He’s followed up with weekly radiotherapy for his cancer recurrence. Prevalence of PHA is 5 – 20 % of hypertensive patients in current literature (1) (2). Normotensive PHA is exceedingly rare, with only about 20 cases reported so far (3). Differential for normotensive hypokalemic patients usually does not ponder PHA, which led to an initial presumptive diagnosis of Gitelmann’s syndrome in our patient. Therefore lack of hypertension in hypokalemic patients should not exclude primary aldosteronism. Primary aldosteronism presenting as a paralytic myopathy, although rare is well established in literature (4) (5). Rhabdomyolysis can often be missed in patients presenting with non-spinal metabolic paralysis associated with hypertension, as symptoms overlap. Tubular vacuoles in kaliopenia of adrenal origin was first observed by Conn and Louis (6). Although literature reveals that early changes are potentially reversible with resurrection of potassium deficit, recovery of damages due to chronic kaliopenia is deemed impossible. This case highlights the importance of investigating for PHA even in patients with normotensive hypokalemia when no other apparent cause is found.

Serum Aldosterone as Predictor of Progression of Coronary Heart Disease in Patients Without Signs of Heart Failure After Acute Myocardial Infarction.

Introduction: In patients with acute myocardial infarction (AMI) early risk assessment of development of complications is of great importance. It is proven that aldosterone level has a major role in progression of cardiovascular pathology. Aim: Determination of influence of aldosterone plasma level in the progression of heart disease in patients without signs of heart failure after AMI. Material and Methods: Research included 207 patients, hospitalized in the acute phase of myocardial infarction, and who were divided into two groups: 127 patients with no clinical signs of heart failure and 60 patients with heart failure. Results: The serum aldosterone concentration was 73.4% higher in the group of decompensated patients, 128 pg/mL (75.4-236 pg/mL) in decompensated and 73.7 pg/mL (42.7 -115.25 pg/mL) in compensated. In the group of compensated patients, changes in aldosterone levels showed a statistically significant effect on the incidence of post-infarction angina (p=0.0001) as well as reinfarction (p=0.009). There is a connection between changes in aldosterone plasma level and positive stress test (p=0.012). Conclusion: In patients with AMI, elevated serum aldosterone level can be prognostic factor of the progression of coronary heart disease, development of heart failure, as well of development of post-infarction angina, myocardial reinfarction and pathological finding on the stress test.

A Case of Near Total Occlusion of the Renal Artery after Endovascular Abdominal Aortic Aneurysm Repair

Endovascular abdominal aortic aneurysm repair is a safe, durable, and effective procedure. However, complications could occur with stent graft devices. When the renal ostia become obstructed by this device, renovascular hypertension may result. In general, renal artery occlusion secondary to stent graft impingement remains uncommon. We herein describe a patient with renal atrophy, new-onset hypertension, and elevated serum renin and aldosterone levels following endovascular aneurysm repair. Blood pressure and the levels of renin and aldosterone were normalized by renal artery stenting.

Renin Inhibition and AT1R blockade improve metabolic signaling, oxidant stress and myocardial tissue remodeling

ObjectiveStrategies that block angiotensin II actions on its angiotensin type 1 receptor or inhibit actions of aldosterone have been shown to reduce myocardial hypertrophy and interstitial fibrosis in states of insulin resistance. Thereby, we sought to determine if combination of direct renin inhibition with angiotensin type 1 receptor blockade in vivo, through greater reductions in systolic blood pressure (SBP) and aldosterone would attenuate left ventricular hypertrophy and interstitial fibrosis to a greater extent than either intervention alone. Materials/MethodsWe utilized the transgenic Ren2 rat which manifests increased tissue expression of murine renin which, in turn, results in increased renin–angiotensin system activity, aldosterone secretion and insulin resistance. Ren2 rats were treated with aliskiren, valsartan, the combination (aliskiren+valsartan), or vehicle for 21days. ResultsCompared to Sprague–Dawley controls, Ren2 rats displayed increased systolic blood pressure, elevated serum aldosterone levels, cardiac tissue hypertrophy, interstitial fibrosis and ultrastructural remodeling. These biochemical and functional alterations were accompanied by increases in the NADPH oxidase subunit Nox2 and 3-nitrotyrosine content along with increases in mammalian target of rapamycin and reductions in protein kinase B phosphorylation. Combination therapy contributed to greater reductions in systolic blood pressure and serum aldosterone but did not result in greater improvement in metabolic signaling or markers of oxidative stress, fibrosis or hypertrophy beyond either intervention alone. ConclusionsThereby, our data suggest that the greater impact of combination therapy on reductions in aldosterone does not translate into greater reductions in myocardial fibrosis or hypertrophy in this transgenic model of tissue renin overexpression.

Autosomal Dominant Pseudohypoaldosteronism Type 1 in an Infant with Salt Wasting Crisis Associated with Urinary Tract Infection and Obstructive Uropathy

Type 1 pseudohypoaldosteronism (PHA1) is a salt wasting syndrome caused by renal resistance to aldosterone. Primary renal PHA1 or autosomal dominant PHA1 is caused by mutations in mineralocorticoids receptor gene (NR3C2), while secondary PHA1 is frequently associated with urinary tract infection (UTI) and/or urinary tract malformations (UTM). We report a 14-day-old male infant presenting with severe hyperkalemia, hyponatremic dehydration, metabolic acidosis, and markedly elevated serum aldosterone level, initially thought to have secondary PHA1 due to the associated UTI and posterior urethral valves. His serum aldosterone remained elevated at 5 months of age, despite resolution of salt wasting symptoms. Chromosomal microarray analysis revealed a deletion of exons 3–5 in NR3C2 in the patient and his asymptomatic mother who also had elevated serum aldosterone level, confirming that he had primary or autosomal dominant PHA1. Our case raises the possibility that some patients with secondary PHA1 attributed to UTI and/or UTM may instead have primary autosomal dominant PHA1, for which genetic testing should be considered to identify the cause, determine future recurrence risk, and possibly prevent the life-threatening salt wasting in a subsequent family member. Future clinical research is needed to investigate the potential overlapping between secondary PHA1 and primary autosomal dominant PHA1.

Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats

Background/AimsMagnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats.MethodsFifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks.ResultsSystolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats.ConclusionsConcurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.

A case of primary aldosteronism presenting as non-ST elevation myocardial infarction

A case of primary aldosteronism presenting as non-ST elevation myocardial infarction

Chronic Growth Hormone Excess Is Associated with Increased Aldosterone: A Study in Patients with Acromegaly and in Growth Hormone Transgenic Mice

Acromegaly is a disease characterized by chronic growth hormone (GH) excess. Since hypertension is a common finding in patients with acromegaly, interactions between GH and the renin-angiotensin-aldosterone system (RAAS) are under controversial debate. We examined GH, IGF-I, aldosterone, and renin in a well-defined group of acromegalic patients before and after cure by surgery. In addition, we analyzed the impact of chronic GH excess on the RAAS in mouse models over-expressing GH alone (G) or in combination with insulin-like growth factor-binding protein-2 (IGFBP-2; GB). Normalization of GH secretion after cure by surgery was accompanied by significant decreases of serum aldosterone in acromegalic patients (pre-op: 96.5 +/- 37.1 pg/mL, post-op: 41.3 +/- 28.2 pg/ mL; P < 0.001; n = 13), but renin concentrations were unaffected. In addition, aldosterone concentrations were positively correlated to GH levels (Spearman r = 0.39; P = 0.025; n = 26). To further study this association, we analysed two transgenic mouse models and found a similar relationship between GH and aldosterone in G mice, which showed about 3-fold elevated serum aldosterone levels in comparison to non-transgenic controls (males: 442 +/- 331 pg/mL vs. 151 +/- 84 pg/mL; P = 0.002; n > or = 12; females: 488 +/- 161 pg/mL vs. 108 +/- 125 pg/mL; P = 0.05; n > or = 4). Expression of aldosterone synthase was similar in adrenal glands of C and G mice. Aldosterone levels in G and GB mice of both genders were not different, indicating that the elevated aldosterone was due to GH excess and not caused by elevated IGF-I, which is known to be blocked by IGFBP-2 overexpression. Also in the mouse models, changes in aldosterone were independent from renin. In summary, we show that chronic GH excess is associated with increased aldosterone in humans and mice. GH-induced increases of aldosterone potentially contribute to the increased cardiovascular risk in acromegalic patients. The underlying mechanism is likely to be independent of renin, excess IGF-I, or adrenal aldosterone synthase expression.

Serum Aldosterone Response to Metoclopramide in Normal Subjects and Acromegalic Patients

The acute effects of metoclopramide on aldosterone and prolactin levels were studied in 11 normal subjects, 8 normotensive and 8 hypertensive acromegalics. Metoclopramide (10 mg i.v.) induced a similar serum aldosterone increase in normal subjects and normotensive acromegalics. Hypertensive acromegalics showed elevated basal serum aldosterone level and blunted aldosterone response to metoclopramide. The prolactin response to metoclopramide was blunted in acromegalics in comparison with normal subjects but the difference was statistically significant only in hypertensive patients. The blunted aldosterone and prolactin responses to metoclopramide in hypertensive acromegalics suggest that there is a dopamine deficiency at central and adrenal level in these patients.

Mineralcorticoid Receptor (MR) Antagonism Attenuates Glomerular Filtration Barrier Remodeling in the Transgenic Ren2 Rat

Renin‐angiotensin‐aldosterone system (RAAS) activation is associated with glomerular filtration barrier/podocyte injury &amp; accompanying proteinuria. To explore potential MR mediated renal effects, Ren2 transgenic rats, which manifest increased tissue RAAS activity with elevated serum aldosterone levels, were used. Six week old Ren2 and Sprague‐Dawley rats were treated with a low dose of the MR antagonist spironolactone (SP)(0.24 mg/day) or vehicle for 21 days. Ren2 rats exhibited albuminuria, loss of podocyte‐specific proteins and podocyte foot‐process effacement on ultrastructural analysis, along with reduced expression of mediators of insulin metabolic signaling. Ren2 kidneys also manifested increased NADPH oxidase/ROS and redox‐sensitive Rho kinase activation in conjunction with enhanced renal tissue levels of MR, angiotensin type 1 receptor, angiotensin II and angiotensin‐(1‐12). SP treatment reduced albuminuria and tissue RAAS expression and improved podocyte structural and protein integrity along with improvements in insulin metabolic signaling. MR blockade directly provides protection in this model of renal RAAS activation, in part, through reductions in redox‐sensitive ROK impairment of insulin metabolic signaling and glomerular remodeling.Supported by NIH R01 HL73101‐01A1 (JRS) &amp; HL‐51952 (CMF), VA Merit (JRS), VA VISN 15 (AWC), &amp; Missouri Kidney Program (AWC).

Mineralocorticoid receptor antagonism attenuates glomerular filtration barrier remodeling in the transgenic Ren2 rat

Recent evidence suggests that mineralocorticoid receptor (MR) antagonism has beneficial effects on tissue oxidative stress and insulin metabolic signaling as well as reducing proteinuria. However, the mechanisms by which MR antagonism corrects both renin-angiotensin-aldosterone system (RAAS) impairments in renal insulin metabolic signaling and filtration barrier/podocyte injury remain unknown. To explore this potential beneficial interactive effect of MR antagonism we used young transgenic (mRen2)27 (Ren2) rats with increased tissue RAAS activity and elevated serum aldosterone levels. Ren2 and age-matched Sprague-Dawley (SD) control rats (age 6-7 wk) were implanted with a low dose of the MR antagonist spironolactone (0.24 mg/day) or vehicle, both delivered over 21 days. Albuminuria, podocyte-specific proteins (synaptopodin, nephrin, and podocin), and ultrastructural analysis of the glomerular filtration barrier were measured in relation to RAAS activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, reactive oxygen species (ROS), and the redox-sensitive Rho kinase (ROK). Insulin metabolic signaling was determined via measurement of insulin receptor substrate-1 (IRS-1) phosphorylation, IRS-1 ubiquitin/proteasomal degradation, and phosphorylation of Akt. Ren2 rats exhibited albuminuria, loss of podocyte-specific proteins, and podocyte foot process effacement contemporaneous with reduced renal IRS-1 and protein kinase B/Akt phosphorylation compared with SD control rats (each P < 0.05). Ren2 kidneys also manifested increased NADPH oxidase/ROS/ROK in conjunction with enhanced renal tissue levels of angiotensin II (ANG II), ANG-(1-12), and angiotensin type 1 receptor. Low-dose spironolactone treatment reduced albuminuria and tissue RAAS activity and improved podocyte structural and protein integrity with improvements in IRS-1/Akt phosphorylation. Thus, in this model of RAAS activation, MR antagonism attenuates glomerular/podocyte remodeling and albuminuria, in part through reductions in redox-mediated impairment of insulin metabolic signaling.

Silencing of the Mineralocorticoid Receptor by Ribonucleic Acid Interference in Transgenic Rats Disrupts Endocrine Homeostasis

Currently, gene disruption by homologous recombination in embryonic stem cells is only feasible in mice. To circumvent this problem, we silenced mineralocorticoid receptor (MR) expression by RNA interference in knockdown rats generated through lentiviral transgenesis. Analysis of the F1 progeny at 3 wk of age revealed strongly decreased MR levels. This was specific for the targeted gene and related to the abundance of the short interfering RNA. Reminiscent of MR knockout mice, the transgenic rats showed a reduced body weight, elevated serum aldosterone levels, increased plasma renin activity, and altered expression of MR target genes. Some of these effects correlated with the degree to which MR mRNA expression was reduced. Whereas disruption of the MR by gene targeting in mice leads to postnatal death, our strategy also allowed obtaining adult knockdown rats with defects in hormone and electrolyte homeostasis resembling pseudohypoaldosteronism. In conclusion, this is the first example of a human disease model based on RNA interference in rats.

Furosemide and the progression of left ventricular dysfunction in experimental heart failure

We tested the hypothesis that furosemide accelerates the progression of left ventricular systolic dysfunction in a tachycardia-induced porcine model of heart failure. Furosemide activates the renin-angiotensin-aldosterone system in patients with congestive heart failure (CHF). Such activation may contribute to CHF progression, but prospective data are lacking. Thirty-two Yorkshire pigs were randomized to furosemide (1 mg/kg intramuscularly daily, mean 16.1 +/- 0.9 mg) or placebo. Thereafter, a pacing model of heart failure was utilized to produce systolic dysfunction in both sets of animals (fractional shortening <0.16 by echocardiogram). The goal was to determine if furosemide would accelerate the progression of left ventricular dysfunction in the "treated" group. After sacrifice, sodium-calcium exchanger currents and their responsiveness to isoproterenol were measured during voltage clamp. All investigators were blinded to treatment assignment. Furosemide shortened the time to left ventricular dysfunction (35.1 +/- 5.1 days in placebo versus 21.4 +/- 3.2 days for furosemide animals; p = 0.038, log-rank test). By day 14, aldosterone levels were significantly higher in furosemide animals (43.0 +/- 11.8 ng/dl vs. 17.6 +/- 4.5 ng/dl; p < 0.05). Serum sodium was reduced (133.0 +/- 0.9 mmol/l furosemide vs. 135.7 +/- 0.8 mmol/l placebo; p < 0.05), but no difference in norepinephrine, potassium, magnesium, creatinine, or urea nitrogen was present. Basal sodium-calcium exchanger currents were significantly increased and isoproterenol responsiveness depressed by furosemide. Tachycardic pigs given furosemide had significant acceleration of both contractile and metabolic features of CHF, including left ventricular systolic dysfunction, elevated serum aldosterone levels, and altered calcium handling in a controlled experimental model of heart failure.

Unilateral adrenal hyperplasia causing primary aldosteronism: limitations of I-131 norcholesterol scanning

Primary aldosteronism is a disorder that is commonly considered in patients referred to the hypertension clinic. The ease of measuring the random aldosterone-to-renin ratio in conjunction with an elevated serum aldosterone level has led to an increased screening for this disorder. Typically, patients undergo a confirmatory test after a positive screening test. However, once primary aldosteronism is confirmed, subtype delineation is critical to decide on the optimal treatment. We report a patient with resistant hypertension and primary aldosteronism with a normal computed tomographic scan of the adrenal glands, a left-sided uptake on adrenal scintigraphy, and a right-sided lateralization of aldosterone after adrenal vein sampling. A repeat adrenal vein sampling confirmed the aldosterone lateralization to the right adrenal gland, which was then removed laparoscopically. The patient had a good clinical and biochemical response, and unilateral adrenal hyperplasia was discovered at histology. Excessive reliance on adrenal scintigraphy without adrenal vein sampling may lead to serious errors in patient management.

Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure

ObjectivesWe sought to compare the neurohormonal responses and clinical effects of long-term, high-dose versus low-dose enalapril in patients with chronic heart failure (CHF). BackgroundExamination of neurohormonal and clinical responses in patients receiving different doses of angiotensin-converting enzyme (ACE) inhibitors may provide insight into the potential for additional suppression with angiotensin II (AT-II) or aldosterone antagonists. MethodsSeventy-five patients with CHF were randomized to receive either high-dose (40 mg/day, n = 37) or low-dose (5 mg/day, n = 38) enalapril over six months. The results from exercise testing, echocardiography, tissue-specific ACE activity and monthly pre- and post-enalapril neurohormonal levels were compared. ResultsDespite greater intra-group improvements in plasma renin activity and serum aldosterone levels in the high-dose group, no statistically significant differences were observed between the two groups in all variables, except for serum ACE activity at the end of study. Elevated serum aldosterone and plasma AT-II levels were observed in 35% and 85% of patients, respectively, at 34 weeks, an inter-group difference that was not statistically significant. A trend toward higher levels of tissue-specific ACE activity in the high-dose group compared with the low-dose group at the end of study was observed (p = 0.054). A predefined composite end point of clinical events had a trend toward better improvement in the high-dose group. ConclusionsThis study could not demonstrate a difference between high- and low-dose enalapril in terms of serum aldosterone and plasma AT-II suppression, despite a dose-dependent reduction in serum ACE activity. Even at maximal doses of enalapril, elevated serum aldosterone and plasma AT-II levels were frequently observed.

Disordered Meibomian Gland Function in Pseudohypoaldosteronism

Several diseases cause a salt-wasting state during infancy, notably with severe diarrhea, endocrine abnormalities (such as congenital adrenal hyperplasia), renal disease, and cystic fibrosis. 1 However, none are associated with a specific eye abnormality. Pseudohypoaldosteronism (PHA) is characterized by salt wasting with hyponatremia and hyperkalemia in the presence of elevated serum aldosterone levels. 2 We report a unique eyelid abnormality resulting from PHA, which may be a valuable clue to the presence of a life-threatening disease, the diagnosis of which can only be made following complex biochemical investigation. Report of a Case. A full-term, 5-day-old male neonate was admitted to the special care baby unit with a white discharge from the eyes and vesicular rash on the scalp and trunk. A row of 0.5-mm white toothlike projections were noted on the margin of all 4 eyelids ( Figure 1 ), consisting of solid columns of white material that were visible within and

Selected mechanisms of diuretic-induced electrolyte changes

Thiazide diuretic therapy has been associated with several biochemical electrolyte imbalances including potassium loss. The onset, duration and magnitude of potassium excretion can influence decisions concerning drug therapy, particularly in hypertensive patients at risk if they develop diuretic-induced hypokalemia. The potassium depletion seen during the course of antihypertensive therapy with thiazides is brought about by 2 primary mechanisms: the increased delivery of sodium to the distal tubules for sodium-potassium exchange, and the development of secondary hyperaldosteronism, which causes resorption of sodium with a loss of potassium into the urine. The diuresis caused by thiazides is maximal between 8 and 12 hours. However, resultant volume contraction stimulates elevated serum aldosterone levels, which can be present for 24 hours or longer. Therefore, potassium loss may exceed the period of diuresis. Diuretics are effective antihypertensive therapy in many patients with mild hypertension. Potassium-sparing agents can offset potassium imbalance that often occurs with diuretics, and thus, these agents have become an important addition to the physician's treatment armamentarium for appropriate patients.