Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: a review

Aldosterone hypersecretion in primary aldosteronism is unilateral (aldosterone producing adenoma and primary unilateral hyperplasia) or bilateral (idiopathic adrenal hyperplasia). Laparoscopic adrenalectomy is nowadays the preferred approach to treat patients with unilateral primary aldosteronism. We review the outcomes of this intervention in recently published series. Laparoscopic adrenalectomy has a morbidity of 5-14%, mortality below 1%, and a mean hospital stay around 3 days. It generally results in the normalization of aldosterone secretion and in a large decrease of blood pressure and antihypertensive medication, but normotension without treatment is only achieved in 42% of all cases. Normotension following adrenalectomy is more likely in young and lean women with recent low grade hypertension than in obese men with long-standing high grade hypertension or a family history of hypertension. However, individual prediction of the blood pressure outcome is not accurate and predictors of hypertension cure should not be used to select patients for surgery. Age, associated health conditions and preferences of the patient are more relevant to this end.     

Twenty-Four hour blood pressure profile in subjects with different subtypes of primary aldosteronism

The aim of our study was to evaluate the potential differences in blood pressure (BP) profile in subjects with different forms of primary aldosteronism (PA). Simultaneously, we studied the effects of PA treatment on BP curve. We therefore monitored 24-hour ambulatory blood pressure values in 22 subjects with aldosterone-producing adenoma (APA), 22 subjects with idiopathic hyperaldosteronism (IHA) and 33 subjects with essential hypertension (EH) as controls. We found a significantly attenuated nighttime systolic BP decline in the APA group (P=0.02). Patients with IHA had lower nighttime systolic BP values (P=0.01) and also a diastolic BP decline (P=0.02) during the night in comparison with EH. We did not detect any significant differences in BP profile characteristics between APA and IHA. Specific treatment of primary aldosteronism (adrenalectomy, treatment with spironolactone) led to the normalization of the BP curve with a marked BP decline. Our study thus demonstrates a blunted diurnal BP variability in patients with primary aldosteronism the specific treatment of which normalized previously attenuated nocturnal BP fall.     

Mineralocorticoid receptor blockade improves diastolic function independent of blood pressure reduction in a transgenic model of RAAS overexpression

There is emerging evidence that aldosterone can promote diastolic dysfunction and cardiac fibrosis independent of blood pressure effects, perhaps through increased oxidative stress and inflammation. Accordingly, this investigation was designed to ascertain if mineralocorticoid receptor blockade improves diastolic dysfunction independently of changes in blood pressure through actions on myocardial oxidative stress and fibrosis. We used young transgenic (mRen2)27 [TG(mRen2)27] rats with increases in both tissue ANG II and circulating aldosterone, which manifests age-related increases in hypertension and cardiac dysfunction. Male TG(mRen2)27 and age-matched Sprague-Dawley rats were treated with either a low dose (～1 mg·kg(-1)·day(-1)) or a vasodilatory, conventional dose (～30 mg·kg(-1)·day(-1)) of spironolactone or placebo for 3 wk. TG(mRen2)27 rats displayed increases in systolic blood pressure and plasma aldosterone levels as well as impairments in left ventricular diastolic relaxation without changes in systolic function on cine MRI. TG(mRen2)27 hearts also displayed hypertrophy (left ventricular weight, cardiomyoctye hypertrophy, and septal wall thickness) as well as fibrosis (interstitial and perivascular). There were increases in oxidative stress in TG(mRen2)27 hearts, as evidenced by increases in NADPH oxidase activity and subunits as well as ROS formation. Low-dose spironolactone had no effect on systolic blood pressure but improved diastolic dysfunction comparable to a conventional dose. Both doses of spironolactone caused comparable reductions in ROS/3-nitrotryosine immunostaining and perivascular and interstitial fibrosis. These data support the notion mineralocorticoid receptor blockade improves diastolic dysfunction through improvements in oxidative stress and fibrosis independent of changes in systolic blood pressure.     

Leptin levels are suppressed in primary aldosteronism.

Primary aldosteronism is associated with hypertension secondary to salt and water retention, hypokalemia and impaired insulin secretion with glucose intolerance in some patients. The secretion of leptin, a hormone produced by adipocytes, may be altered by reduced insulin secretion in primary aldosteronism. We measured plasma leptin approximately 3 months before and 3 months after curing of primary aldosteronism in 18 patients (12 male, 6 female, body mass index 29.1+/-4.4, mean +/- SD). Patients were treated by unilateral laparoscopic adrenalectomy to remove an aldosterone-producing adenoma. There was a 46% postoperative increase in plasma leptin concentrations from 6.65+/-0.81 to 9.68+/-1.50 ng/ml (P=0.004), despite a non-significant fall in body mass index. Plasma leptin was noted to increase after adrenalectomy in 16 of the 18 patients. The patients also had improved blood pressure and a significant increase in plasma potassium post-operatively. It is proposed that increased insulin secretory capacity associated with correction of negative potassium balance may account for the increase in plasma leptin after curing primary aldosteronism. Further studies are indicated to identify the mechanism of plasma leptin suppression in primary aldosteronism.     

培哚普利联合螺内酯治疗非腺瘤型原发性醛固酮增多症的临床疗效研究

目的:研究培哚普利联合螺内酯治疗非腺瘤型原发性醛固酮增多症患者的临床效果及安全性。方法:选取在我院进行诊治的62例非腺瘤型原发性醛固酮增多症患者并将其随机分为对照组和观察组,每组31例。对照组患者在常规治疗方案的基础上给予20 mg螺内酯口服,一天3次;观察组患者在对照组的基础上加用4 mg培哚普利口服,一天1次。所有患者均治疗3个月,观察和比较两组的临床疗效,治疗前后血压、心功能、血钾、6分钟步行试验结果的变化。结果:(1)治疗后,对照组临床总有效率为74.2%(23/31),较观察组[93.5%(29/31)]显著降低(P0.05);(2)治疗后,两组患者收缩压和舒张压、LVESD(左室收缩末期内径)、LVEDD(左室舒张末期内径)均显著低于治疗前(P0.05),而LVEF(左室射血分数)、血清钾浓度、6分钟步行距离均显著高于治疗前(P0.05),且观察组患者收缩压和舒张压、LVEDD、LVESD均明显低于对照组,而LVEF、血清钾浓度、6分钟步行距离均显著高于对照组(P0.05);(3)治疗过程中,对照组患者不良反应发生率为6.5%(2/31),观察组为12.9%(4/31),两组之间比较差异无统计学意义(P0.05)。结论:培哚普利联合螺内酯治疗非腺瘤型原发性醛固酮增多症患者可显著提高其临床疗效,改善患者心功能,并有效降低血压,且安全性高。     

Role of atrial natriuretic peptide in mineralocorticoid escape phenomenon in patients with primary aldosteronism

The withdrawal effect of spironolactone treatment on natriuresis was studied in relation to atrial natriuretic peptide (ANP) in five patients with primary aldosteronism due to adenoma. The patients had been treated with spironolactone for 2-3 months before they were admitted. After admission, blood pressure, body weight, and urinary excretion of sodium were measured daily. Venous samples were obtained twice a week for measurements of plasma levels of ANP, plasma renin activity (PRA), and plasma concentrations of aldosterone (PAC), cortisol, and deoxycorticosterone. The study was performed for 7 days during the treatment with spironolactone and for 18 days after stopping the administration. Plasma volume was determined two times, during the control period and on the 13th day after stopping spironolactone. Urinary sodium excretion decreased initially and returned to the control levels successively. Body weight and plasma volume increased, and blood pressure rose steadily. PRA and the plasma concentrations of cortisol and deoxycorticosterone decreased significantly (P less than 0.05); however, high levels of PAC did not alter significantly. Plasma ANP levels increased significantly (P less than 0.05) from 26 +/- 4 pg/ml during the control period to 195 +/- 47 pg/ml on the 13th day after stopping spironolactone. The data of the urinary sodium excretion showed the escape from sodium-retaining effect of aldosterone, and this escape could be explained by the increase in plasma ANP. Furthermore, ANP might contribute to the decrease in cortisol and deoxycorticosterone in plasma because of the direct inhibitory action of ANP on steroidogenesis.     

两种腹腔镜肾上腺切除术式治疗原发性醛固酮增多症效果评价

目的：比较腹腔镜肾上腺全切术与部分切除术治疗原发性醛固酮增多症的效果。方法：对152例原发性醛固酮增多症分别采用肾上腺全切术（A组82例）和肾上腺部分切除术（B组70例）进行治疗,测量并比较两组患者手术时间、手术失血量、住院时间以及术后一月内血压恢复者比例。结果：两组患者性别、年龄、高血压和低血钾在组间情况无统计差异,具备可比性（P〉0．05）。A组患者手术时间、术后一月内血压恢复比例高于B组（P〈0．05）,而失血量和住院时间无组间差异（P〉0．05）。结论：在腹腔镜肾上腺切除手术中,肾上腺全切取得了较好的效果,具有较高的临床应用价值。     

Effect of stress management on blood pressure in mild primary hypertension.

OBJECTIVE--To establish whether stress management had a larger effect than a control treatment on resting blood pressure, ambulatory blood pressure, and left ventricular mass. DESIGN--A 12 week baseline period of habituation to measurement of blood pressure was followed by randomisation to either stress management or mild exercise for six months and follow up six months later. SETTING--General practice, district general hospital, and medical school. PATIENTS--Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period, 88 were excluded because they failed to meet the entry criteria or they withdrew from the study. The remaining 46 men and 50 women underwent treatment. INTERVENTIONS--10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises. Mildly stressful 15 minute interviews before and after treatment. MAIN OUTCOME MEASURES--Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording, and left ventricular mass measured by echocardiography. RESULTS--The patients'' blood pressure fell during habituation (systolic pressure from 152 mmHg to 140 mmHg, diastolic pressure from 98 to 93 mm Hg), but neither resting nor ambulatory blood pressure was changed by the treatments. Left ventricular mass was also unchanged. Blood pressure rose during the stressful interview, but this rise was reduced by stress management (systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment). CONCLUSION--Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure.     

Comparison of Surgery and Prolonged Spironolactone Therapy in Patients with Hypertension,Aldosterone Excess,and Low Plasma Renin

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery.Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment.In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied.Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped.In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.     

Results of adrenal surgery in patients with hypertension,aldosterone excess,and low plasma renin concentration.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.     

树脂灌血液灌流在顽固性高血压患者血液透析中的应用

目的：探讨树脂灌血液灌流对血液透析顽固性高血压患者血压及肾素-血管紧张素．醛固酮系统的影响。方法：选择我院82例,均分为I组和II组各41例,I组患者采用金宝8LR聚酰胺膜透析器进行常规透析,II组患者在常规透析的基础上串联树脂血液灌流,检测两组患者治疗前和治疗后3个月血清肌酐、尿素氮变化情况,和患者体内肾素活性、血管紧张素II和醛固酮变化情况,并对血压变化值进行比较。结果：两组患者治疗后3个月血肌酐、血尿素氮均明显较治疗前降低,I组患者治疗后3个月收缩压和舒张压较治疗前均无明显变化,II组治疗后3个月收缩压和舒张压均较治疗前明显降低,I组治疗后3个月肾素、血管紧张素II和醛固酮较治疗前无明显差异,II组治疗后3个月肾素、血管紧张素II和醛固酮较治疗前均明显降低。结论：血液透析联合树脂吸附灌在保证有效清除患者体内代谢物质的同时角色较好的控制患者血压。     

An easy diagnostic approach to primary aldosteronism.

The infusion of 40 mEq potassium (aspartate) in 250 ml isotonic 1-fructose at a rate of 20 mEq/h into 5 patients (34-56 years old) with aldosteronoma and 2 patients with bilateral primary aldosteronism consistently raised their mean arterial pressure by 15-20 mmHg. Their pressure values returned to the baseline levels 4-5 h after the infusion. In contrast, in controls (10 patients with idiopathic arterial hypertension, matched for age, sex, and magnitude of the untreated hypertension, and 7 patients with inactive adrenal nodules as incidental findings on upper abdomen ultrasound or computerized tomography) the same procedure caused negligible arterial pressure changes. The cause of the rise in blood pressure observed uniquely in patients with primary aldosteronism after infusion of potassium (aspartate) cannot be accounted for by an increase in plasma aldosterone, blood volume, or plasma angiotensin II. The cause of this response thus remains obscure; nonetheless, this simple procedure may prove useful in differentiating primary aldosteronism from idiopathic hypertension, in excluding the adrenal disorder, and in revealing even its mildest forms.     

Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats

It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.     

Medium-term cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children

AIM: To investigate the possible cardiac morphofunctional alterations inducd by prolonged and high-dose GH therapy in a group of 14 children with isolated GH deficiency. PATIENTS AND METHODS: Patients were evaluated at phase 1, after 1.1 +/- 0.6 years of treatment with GH 0.93 +/- 0.13 U/kg/week, and at phase 2, after 5.5 +/- 2.1 years of therapy 0.89 +/- 0.11 U/kg/week. At each phase left ventricular volume, mass and systolic function were evaluated by two-dimensional guided M-mode echocardiography; left ventricular diastolic function was assessed by PW-Doppler sampling of transmitral flow. RESULTS: Phase 1: diastolic blood pressure was lower (p < 0.05) and fractional shortening was not adequate for the level of afterload (stress shortening index p < 0.05) in patients compared to controls. Phase 2: diastolic blood pressure was lower (p < 0.01) and mass and mass/volume ratio were increased (mass index p < 0.05, mass/ volume ratio p < 0.05) in patients compared to controls. The increased mass/volume ratio, together with the normal systolic blood pressure, explains the reduction in peak systolic stress (p < 0.005). Among the parameters of left ventricular diastolic function, the peak E velocity/total area under mitral valve tracing and the area under E velocity/total area under mitral value tracing ratios were significantly decreased (p < 0.05). CONCLUSION: After a mean period of 5 years on high-dose GH treatment in GH-deficient children, subclinical morphofunctional alterations in the left ventricle were found.     

Prevalence,Subtype Classification,and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA.MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018.ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups.ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.     

A case of primary aldosteronism with chronic renal failure undergoing hemodialysis treatment

A 56-year-old man with primary aldosteronism and chronic renal failure undergoing hemodialysis is described. He complained of numbness of the extremities and showed persistent hypopotassemia in spite of anuria. In the endocrinological examination, a very high plasma aldosterone concentration was observed, while plasma renin activity was within the normal range. From the abdominal Computed Tomography (CT), adrenal scintigraphy, and segmental venous sampling data, he was diagnosed as primary aldosteronism due to left adrenocortical adenoma. In this case, hypopotassemia could not be explained by potassium loss through the kidneys, which suggests potassium excretion in the gastrointestinal tract as the mechanism of hypopotassemia. This was clearly shown from a potassium-balance study and the results of spironolactone administration. Our report is on the first case showing hypopotassemia due to primary aldosteronism in spite of anuria. If a patient treated with maintenance dialysis should have persistent hypopotassemia, as in the present report, it is necessary to consider an association with primary aldosteronism.     

Adrenal aldosterone-producing adenoma: use of colonic potential in diagnosis and subtraction scanning technique for localisation.

Primary hyperaldosteronism is a potentially curable cause of hypertension, and much interest has been shown in methods of diagnosing the associated hypokalaemic hypertension and localising the adrenal adenoma. In two patients the diagnosis of primary aldosteronism was confirmed by colonic potential measurement and the adenoma localised by a new subtraction technique for early adrenal imaging applied to the use of 131I-19-iodocholesterol. Both patients underwent adrenalectomy and in each case an adenoma was removed. Blood pressure and electrolyte levels returned to normal after operation. In one patient bilateral adrenal phlebography had failed to show the tumour, and sampling of aldosterone concentrations in the adrenal veins had been unsatisfactory.     

Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension

N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.     

Working heart function in diabetes is not improved by spironolactone treatment

Aldosterone antagonism has emerged as an important strategy for end-stage congestive heart failure. To evaluate the potential contribution of aldosterone towards the cardiac complications of diabetes, this study examined the effects of chronic aldosterone receptor blockade (with spironolactone) on isolated working heart function in streptozotocin (STZ) - induced diabetic rats. Wistar rats were divided into four groups: control, control spironolactone-treated, diabetic, and diabetic spironolactone-treated. Following chronic spironolactone treatment (8 weeks), cardiac function was assessed in terms of the rate of contraction (+dP/dT), rate of relaxation (-dP/dT), and left ventricular developed pressure (LVDP). Untreated diabetic rats exhibited marked cardiac dysfunction when compared with age matched controls (p < 0.001). Long-term spironolactone treatment did not improve these parameters. These data demonstrate the lack of beneficial effects of aldosterone receptor blockade on isolated working heart function in diabetes.     

Prolonged pseudoaldosteronism induced by glycyrrhizin.

We describe the natural recovery from the aggravated hypertension, hypokalemia and suppression of the renin-aldosterone axis after the glycyrrhizin discontinuation in two mild hypertensive women aged 71 and 68 years, who had been administered 273 to 546 mg glycyrrhizin daily for 1.5 and 6 months, respectively, for the treatment of liver disease. About one month after the glycyrrhizin discontinuation, acceleration of hypertension, hypokalemia and suppression of the renin-aldosterone system still continued in both patients. At this stage, sodium restriction resulted in the normalization of blood pressure with weight loss and the subsequent sodium repletion produced a rapid increase in blood pressure to hypertensive levels observed before sodium restriction, with weight gain. Plasma renin activity and plasma aldosterone were low and did not respond to sodium restriction. Inappropriately excessive amounts of potassium were also excreted in the presence of hypokalemia. About one and a half months later, the improvements of aggravated hypertension, hypokalemia and suppressed renin-aldosterone system gradually occurred in both patients. Sodium restriction performed about three months later in case 2 no longer produced the changes in blood pressure and body weight. Plasma renin activity and plasma aldosterone responded subnormally to sodium restriction. These results demonstrate that both patients had a prolongation of the syndrome resembling primary aldosteronism except the low plasma aldosterone level about one month after the glycyrrhizin discontinuation. The possible mechanisms by which this prolongation was caused are discussed.