OBJECTIVETo investigate the clinical features of adrenocortical adenoma's diagnosis and treatment in patients aged 60 years or above.

METHODSA retrospective study was performed with a total of 249 patients aged 60 years or above who suffered from adrenocortical adenoma and treated in Peking Union Medical College Hospital from January 2004 to January 2014.The clinical features, treatments and prognosis of the 249 patients aged 60 years or above were compared with another 249 patients which were randomly selected during the same period aged from 30 to 50 years.t-test or χ(2) test was used to analyze the data between the two groups.

RESULTSEndocrine examinations were performed in all 249 patients aged 60 years or above.There were 144 patients diagnosed as non-functional adrenocortical adenoma, 94 cases as aldosterone-producing adenoma and 11 cases as Cushing adenoma.For the patients aged 60 years or above, the rate of cardio-cerebral vascular incident in non-functional adrenocortical adenoma group was 26.4%(38/144), which was significantly lower than that of the aldosterone-producing adenoma and Cushing adenoma group(54.3%, 57/105)(χ(2)=20.027, P=0.000). There were 91.5%(65/71) of the patients aged 60 years or above who got a relief in low blood potassium symptoms after the operation.Forty-nine point one percent(53/108) of the non-functional adrenocortical adenoma patients aged 60 years or above had a better control of their blood pressure level, while functional adrenocortical adenoma group were 64.0%(48/75) which indicated that the functional adrenocortical adenoma patients have a better control of their blood pressure then the non-functional adrenocortical adenoma patients after the operation(χ(2)=3.987, P=0.046). There were 37.1% of the patients aged 60 years or above whose fasting blood-glucose was higher than 7.1 mmol/L, while the patients aged from 30 to 50 years was 14.1%(χ(2)=22.02, P=0.000). The differences in plasma aldosterone and blood potassium between the patients aged 60 years or above and the patients aged from 30 to 50 years had statistical significance(t=10.48, -2.58; P=0.00, 0.01).

CONCLUSIONSMost of the adrenocortical adenoma in patients aged 60 years or above is non-functional adrenocortical adenoma.Among who, patients with aldosterone-producing adenoma tend to have lower plasma aldosterone concentration and higher blood potassium level then the patients aged from 30 to 50 years.The patients aged 60 years or above with functional adrenocortical adenoma are tend to have severe cardio-cerebral vascular incidence.A few of non-functional adrenocortical adenoma patients who combine with hypertension can benefit for the operation.

Adrenocortical Adenoma ; diagnosis ; therapy ; Adult ; Aldosterone ; metabolism ; Blood Pressure ; Humans ; Hypertension ; Middle Aged ; Prognosis ; Retrospective Studies

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na⁺ by the epithelial Na⁺ channel (ENaC) located at the apical membrane of principal cells. When Na⁺ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K⁺ efflux, H⁺ efflux, and Cl^- influx are the 3 pathways that respond to Na⁺ influx, that is, all these 3 pathways are coupled to Na⁺ influx. In general, Na⁺ influx is equal to the sum of K⁺ efflux, H⁺ efflux, and Cl^- influx. Therefore, any alteration in Na⁺ influx, H⁺ efflux, or Cl^- influx can affect K⁺ efflux, thereby affecting the renal K⁺ excretion. Firstly, Na⁺ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na⁺ reabsorption, K⁺ excretion, as well as H⁺ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na⁺ and decreased excretion of both K⁺ and H⁺, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na⁺ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na⁺-K⁺-2Cl^- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na⁺-Cl^- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na⁺ by ENaC at the collecting duct, as well as increased excretion of K⁺ and H⁺, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl^- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H⁺ decreases. Both above conditions can lead to increased K⁺ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.
Humans ; Bartter Syndrome/metabolism* ; Pseudohypoaldosteronism/metabolism* ; Potassium/metabolism* ; Aldosterone/metabolism* ; Hypokalemia/metabolism* ; Gitelman Syndrome/metabolism* ; Hyperkalemia/metabolism* ; Clinical Relevance ; Epithelial Sodium Channels/metabolism* ; Kidney Tubules, Distal/metabolism* ; Sodium/metabolism* ; Hypertension ; Alkalosis/metabolism* ; Water/metabolism* ; Kidney/metabolism*

AIMTo investigate the effects of pravastatin on endothelin(ET) expression induced by aldosterone in cultured neonatal rat cardiac fibroblasts.

METHODSET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 (ppET-1) was detected and quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) method.

RESULTSThe cardiac fibroblasts, treated with aldosterone at 107 mol/L, significantly up-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release. Pravastatin (10(-5), 10(-4), 10(-3) mol/L) dose-dependently blocked these effects. In contrast, pravastatin-induced inhibitory effects were reversed in the presence of mevalonate.

CONCLUSIONPravastatin down-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.

Aldosterone ; metabolism ; Animals ; Cells, Cultured ; Endothelins ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Myoblasts, Cardiac ; drug effects ; metabolism ; Pravastatin ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect and related mechanisms of aldosterone (ALD) on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production in aortic adventitia.

METHODSAortic adventitias from SD rats were incubated for 6 hours with various protocols: buffer alone (control), ALD (10(-8) mol/L - 10(-6) mol/L), ALD + spironolactone (10(-5) mol/L, ALD + SP), ALD + RU486 (10(-5) mol/L), LPS 10 ng/ml (LPS), ALD + LPS (10 ng/ml), ALD + LPS + SP (10(-5) mol/L), and ALD + LPS + RU486. Nitrate/nitrite (NOx), an index of NO production, was measured by Greiss Reaction. iNOS activity was determined by isotope-labeled L-arginine convertion rate.

RESULTS(1) NOx production and iNOS activity were similar between ALD and control groups (P > 0.05). NOx production was significantly reduced while iNOS activity remained unchanged in the ALD (10(-6) mol/L) + SP group compared to ALD (10(-6) mol/L) group. NOx production by 10(-7) mol/L and 10(-6) mol/L ALD increased by 50.0% and 58.7% respectively (P < 0.01) and iNOS activity was also significantly increased (P < 0.01) in ALD + RU486 group than that in ALD group. (2) LPS significantly increased the NOx production and iNOS activity (P < 0.01) and these effects were not augmented by adding ALD to LPS (P > 0.05) and SP significantly blocked and RU486 significantly enhanced the effects by LSP and ALD on NOx production and iNOS activity (P < 0.05).

CONCLUSIONAldosterone has a dual effect on iNOS/NO through mineralocorticoid receptor and glucocorticoid receptor pathway.

Aldosterone ; pharmacology ; Animals ; Aorta, Thoracic ; metabolism ; Cells, Cultured ; Connective Tissue ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley

Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy (LVH) and its possible mechanism--inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRs were used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stained with HE method and VanGieson method. Collagen volume fraction was determined in the left ventricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measured by radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited higher SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P < 0.05). After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, and aldosterone concentration in SHR were decreased as compared with control group (P < 0.05) except SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ventricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. The mechanism was probably related with the inhibition of the cardiac aldosterone action.
Aldosterone ; metabolism ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hypertension ; metabolism ; physiopathology ; Hypertrophy, Left Ventricular ; metabolism ; prevention & control ; Male ; Myocardium ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Salvia miltiorrhiza

Patients suffering from idiopathic or self-induced edema are uniformly characterized by chronic use of furosemide, which leads to vicious cycle of edema. Among chronic furosemide users who don't have any other specific edema forming diseases, 9 patients from the outpatient clinic(OC) and 6 patients examined at the emergency room(ER) used it mainly for weight reduction and for cyclical edema, respectively. All of the ER group patients were presented with severe hypokalemia(2.04+/-0.2mEq/L; range 1.3 to 2.7 mEq/L) and alkalosis(748+/-0.01; range 7.44 to 7.51) but none from the OC group showed such results. Other baseline parameters including Plasma renin activity(PRA) and aldosterone level on recumbency, and FEn(2)were similar in both groups. In contrast, daily working hours(6.1+/-0.5 vs 10+/-0.6hr, p<0.01), average body weight gain between AM and PM(0.4+/-0.1 vs 0.9+/-0.lkg, p<0.01), peak weight gain interval(9+/-0.8 vs 5+/-0.1day, p<0.05), PRA(7.6+/-1.5 vs 23.5+/-7.2ng/ml/h, p<0.05) and aldosterone level(22.1+/-4.2 vs 64.8+/-10.4 ng/dl, p<0.01) on ambulation, and FEk. on normokalemia(ll+/-2A vs 36+/-7.7%, p<0.01) were statistically different between the two groups. In comparison to the OC group, both the amout of urine(617+/-39 vs 358+/-26ml, p<0.01) and the percent change of PRA(-14+/-4 vs -3+/-2%, p<0.05) and al-dosterone level(-17+/-5 vs -4+/-3%, p<0.05) after saline loading(lL over 1hr, IV) following ambulation were smaller in the Elt group. Moat of the ER group patients(5/6) required aldosterone antagonist (spironolactone) added to K+ supplement, but all of the OC group patients were managed to maintain an edema-free status with conservative treatment. In conclusion, patients with idiopathic edema seem to have more fluid transudation out of intravascular space during orthostasis with a prominent degree of deranged renin-aldosterone axis and K+ metabolism than those with self-induced edema.
Aldosterone ; Axis, Cervical Vertebra ; Body Weight ; Dizziness ; Edema* ; Emergencies ; Furosemide* ; Humans ; Metabolism ; Outpatients ; Plasma ; Renin ; Walking ; Weight Gain ; Weight Loss

BACKGROUND: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. METHODS: Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=−0.366, P=0.068 and β=−0.252, P=0.070, respectively). CONCLUSION: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.
Adenoma ; Aldosterone ; Calcium* ; Heart Diseases ; Homeostasis ; Humans ; Hyperaldosteronism* ; Hypercalciuria ; Hyperplasia ; Hypocalcemia ; Metabolism* ; Parathyroid Hormone ; Plasma ; Prevalence ; Renin ; Veins

BACKGROUNDHypertension often persists after adrenalectomy for primary aldosteronism (PA). Many studies have analyzed the outcomes of adrenalectomy for aldosterone-producing adenomas (APA) to identify predictive factors for persistent hypertension. However, differentially expressed genes in persistent postoperative hypertension remain unknown. Our aim was to describe gene expression profile of persistent postoperative hypertension patients with APA.

METHODSIn this study, we described and compared gene expression profiles in persistent postoperative hypertension and postoperative normotension in Chinese patients with APA using microarray analysis. Confirmation was performed with quantitative real time-polymerase chain reaction analysis. Bioinformatic analysis (gene ontology analysis, pathway analysis and network analysis) was used for further research.

RESULTSMicroarray analysis identified a total of 99 differentially expressed genes, including 18 up-regulated and 81 down-regulated genes. Among the dysregulated genes were fat atypical cadherin 1 as well as fatty acid binding protein 4 and other genes that have not been previously studied in persistent postoperative hypertension with APA. Bioinformatics analysis indicated that differentially expressed genes were associated with lipid metabolic process, metal ion binding, and cell differentiation. Pathway analysis determined that five pathways corresponded to the dysregulated transcripts. The mRNAs-ncRNAs co-expression network was composed of 49 network nodes and 72 connections between 18 coding genes and 31 noncoding genes.

CONCLUSIONSThis study revealed differentially expressed genes in persistent postoperative hypertension with APA and provided a resource of candidate genes for exploration of possible drug targets and prognostic markers.

Adenoma ; metabolism ; physiopathology ; surgery ; Adrenalectomy ; Aldosterone ; metabolism ; Blood Pressure ; physiology ; Gene Expression Profiling ; methods ; Humans ; Hyperaldosteronism ; metabolism ; physiopathology ; surgery ; Postoperative Complications ; Retrospective Studies

Chronic stable diabetic patients (n = 6) were compared with healthy control subjects (n = 5) after acute oral intake of 50 mEq of potassium chloride (KCl) to investigate for possible derangements of homeostatic responses for acute term (3 hrs) to acute potassium load. Plasma renin activity (PRA), plasma aldosterone (PA), and transtubular potassium concentration gradient (TTKG) known as a useful semiquantative index of distal nephron potassium secretion were measured. All the baseline parameters were comparable between diabetic and non-diabetic subjects except for significantly reduced creatinine clearance in diabetics (mean +/- SEM, 105 +/- 4 vs. 85 +/- 5 ml/min, p < 0.05). Following acute oral KCl load, the peak increases of serum potassium changes from basal levels were noted at 2 hours in both groups, but were higher in diabetic subjects (mean +/- SEM, 0.42 +/- 0.06 vs. 0.62 +/- 0.09 mEq/L). Also, 4 out of 6 diabetic subjects but none of the control subjects at 2 hours after oral KCl load became hyperkalemic ( > 5.0 mEq/L). PRA did not show any significant changes, whereas PA was increased simultaneously with increments in serum potassium in both groups, with blunted increases in the diabetics. However, TTKG was increased prominently in control subjects (8.18 from 4.98), but only slightly in diabetic subjects (4.55 from 4.18), with statistical difference between the two groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Aldosterone/blood ; Diabetes Mellitus, Type 2/*metabolism ; *Homeostasis ; Humans ; Kidney Tubules/metabolism ; Male ; Middle Aged ; Potassium/*metabolism ; Renin/blood

No abstract available.
Adrenal Cortex Neoplasms/diagnosis/*metabolism/surgery ; Adrenalectomy ; Adrenocortical Adenoma/diagnosis/*metabolism/surgery ; Adult ; Aldosterone/*biosynthesis ; Cushing Syndrome/diagnosis ; Female ; Humans ; Hydrocortisone/*biosynthesis ; Hyperaldosteronism/metabolism