Lateralisation of aldosterone-producing adenoma in primary aldosteronism

Four lateralizing methods were carried out in 14 patients with primary aldosteronism (PA): ultrasonography, CT scan, adrenal scintiscan and determination of adrenal venous aldosterone levels. In all cases, unilateral aldosterone-producing adenomas were verified by surgery. Of four lateralizing methods, determination of adrenal venous aldosterone, in spite of high diagnostic value, has two big problems: difficulty in selective catheterization of right adrenal vein and dilution of adrenal vein efflux from non-adrenal sources. To solve these problems, cortisol (C, micrograms/dl) levels along with aldosterone (A, ng/dl) were determined in samples from the left adrenal vein (LAV) and the inferior vena cava (IVC) in 8 patients with PA, and the (LAV A/C)/(IVC A/C) ratio was calculated. That ratio was also obtained in 7 patients with other types of hypertension for comparison. Accuracy of lateralisation by ultrasonography, CT scan and adrenal scintiscan was 23%, 64% and 69% respectively, in the first studies. Those rates changed to 23%, 93% and 85% when the second studies were performed. Venous blood was obtained from both adrenal veins in 46% (6/13), while lateralisation of adenoma was also predicted in 46% (6/13) by the measurement of aldosterone concentrations alone. On the other hand, (LAV A/C)/(IVC A/C) ratios were 3.54-6.98 in the cases of left APA, 0.15-0.98 in those of right APA and 1.10-2.86 in cases of other types of hypertension. There was no overlap of ratios among the three groups, resulting in correct prediction of lateralisation in all cases (8/8) of APA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a test using saralasin to differentiate primary aldosteronism due to an aldosterone-producing adenoma from idiopathic hyperaldosteronism

We evaluated a new method utilizing saralasin to differentiate primary aldosteronism due to an aldosterone-producing adenoma from idiopathic hyperaldosteronism. The test is based on the marked difference in sensitivity to angiotensin II of aldosterone-producing adenomas and hyperplastic adrenal glands and the partial angiotensin II agonist property of saralasin in low-renin states. Saralasin was infused into 14 patients with primary aldosteronism and the plasma aldosterone responses determined. Plasma aldosterone concentration increased in all eight patients with idiopathic hyperaldosteronism, whereas there was no increase in plasma aldosterone in six patients who had a solitary adenoma. We concluded that saralasin may be a clinically useful, noninvasive tool to distinguish patients with an aldosterone-producing adenoma from those who have idiopathic hyperaldosteronism.     

Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism.

Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent-genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications.     

Pre-operative evaluation of the prognosis of hypertension in primary aldosteronism owing to adenoma

The prognosis of hypertension was evaluated pre-operatively in 40 patients with primary aldosteronism owing to adenoma by examining the severity of hypertension, family history of hypertension, age of the patients, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and efficacy of spironolactone (100 mg per day for 10 days) on blood pressure. In 30 of the 40 patients, the blood pressure was reduced to below 160/95 mmHg within a year after adrenalectomy (responders). In the other 10 patients, the blood pressure was not markedly reduced and remained above 160/95 mmHg (nonresponders). There were no significant differences in the age of the patients, family history of hypertension, plasma renin activity or plasma aldosterone concentration between these two groups. The severity of hypertension as judged by the WHO classification and the duration of hypertension prior to operation seemed to be of some use in assessing the postoperative prognosis of hypertension, but the efficacy of spironolactone was far more useful. That is to say, a reduction in mean blood pressure of more than 15 mmHg after administration of spironolactone was observed in 29 of the 30 responders. The remaining one patient showed an 11 mmHg reduction in mean blood pressure. On the other hand, none of the nonresponders revealed a reduction in mean blood pressure of more than 15 mmHg after spironolactone administration. From these results it is concluded that the pre-operative response of blood pressure to administration of 100 mg per day of spironolactone for 10 days represents a useful indicator of the postoperative prognosis of hypertension in patients with primary aldosteronism owing to adenoma.     

Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma

Type 1 diabetes triggers protein kinase C (PKC)-dependent NADPH oxidase activation in the renal medullary thick ascending limb (mTAL), resulting in accelerated superoxide production. As acute exposure to superoxide stimulates NaCl transport by the mTAL, we hypothesized that diabetes increases mTAL Na(+) transport through PKC-dependent and NADPH oxidase-dependent mechanisms. An O(2)-sensitive fluoroprobe was used to measure O(2) consumption by mTALs from rats with streptozotocin-induced diabetes and sham rats. In sham mTALs, total O(2) consumption was evident as a 0.34±0.03 U change in normalized relative fluorescence (ΔNRF)/min per mg protein. Ouabain (2 mmol/L) reduced O(2) consumption by 69±4% and 500 μmol/L furosemide reduced O(2) consumption by 58±8%. Total O(2) consumption was accelerated in mTAL from diabetic rats (0.74±0.07 ΔNRF/min/mg protein; P<0.05 versus sham), reflecting increases in ouabain- and furosemide-sensitive O(2) consumption. NADPH oxidase inhibition (100 μmol/L apocynin) reduced furosemide-sensitive O(2) consumption by mTAL from diabetic rats to values not different from sham. The PKC inhibitor calphostin C (1 μmol/L) or the PKCα/β inhibitor G?6976 (1 μmol/L) decreased furosemide-sensitive O(2) consumption in both groups, achieving values that did not differ between sham and diabetic. PKCβ inhibition had no effect in either group. Similar inhibitory patterns were evident with regard to ouabain-sensitive O(2) consumption. We conclude that NADPH oxidase and PKC (primarily PKCα) contribute to an increase in O(2) consumption by the mTAL during type 1 diabetes through effects on the ouabain-sensitive Na(+)-K(+)-ATPase and furosemide-sensitive Na(+)-K(+)-2Cl(-) cotransporter that are primarily responsible for active transport Na(+) reabsorption by this nephron segment.     

Primary aldosteronism with aldosterone-producing adrenal adenoma in a pregnant woman

A 30-year-old pregnant woman complained of muscle weakness at 29 weeks' gestation. She was hypertensive with severe hypokalemia. Lower plasma renin activity and higher aldosterone level than the normal values in pregnancy suggested primary aldosteronism. A cesarean delivery was performed at 31 weeks' gestation because of pulmonary congestion. The neonatal course was uncomplicated. The laparoscopic adrenalectomy for a 2.0-cm right adrenal adenoma resulted in normalizing of her blood pressure and serum potassium level. Although primary aldosteronism is rare, especially during pregnancy, it should be always considered as one of etiologies of hypertension in pregnancy.     

Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone-producing adenoma

BACKGROUND: Data on the performance of the tests used to confirm the diagnosis of primary aldosteronism (PA) are limited. OBJECTIVE: To prospectively investigate the accuracy of the saline infusion test (SIT). METHODS: Three hundred and seventeen (26.9%) out of 1125 patients screened in the PAPY study underwent measurement of plasma aldosterone, cortisol and renin activity after infusion of 2 l of isotonic saline intravenously over 4 h. They comprised patients with a baseline aldosterone/renin ratio (ARR) > 40 and one every four patients not fulfilling such criterion. The area under the receiver-operator characteristic curves (AUC) of aldosterone values after SIT was used as a measure of accuracy for diagnosing PA, aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). RESULTS: One hundred and twenty (37.9%) patients had PA that was due to an APA in 46 (38.3%) and to IHA in 74 (61.7%). No untoward effect occurred with the SIT. The AUC (0.811 +/- 0.026, 0.878 +/- 0.040 and 0.784 +/- 0.034 for identification of PA, APA and IHA, respectively) was higher (P < 0.0001) than that under the diagonal. By sensitivity/specificity versus criterion values plot, the best aldosterone cut-off values for identifying APA and IHA were 6.75 and 6.91 ng/dl, respectively. However, even at these optimal cut-offs, sensitivity and specificity were moderate because of values overlapping between patients with and without the disease. Moreover, there were no differences of AUC and aldosterone cut-offs between APA and IHA. CONCLUSION: In a multicenter study the SIT was safe and specific for excluding PA, but had no place for discriminating between an APA and IHA.     

Plasma immunoreactive proopiolipomelanocortin-derived peptides in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.     

Controlled study of circadian rhythm of blood pressure in patients with aldosterone-producing adenoma compared with those with essential hypertension

OBJECTIVE: The circadian rhythm of blood pressure in patients with aldosterone-producing adenoma (APA) is not well understood. We evaluated the circadian blood pressure rhythm in such patients by comparison with that in patients with essential hypertension (EHT). The latter are characterized by a nocturnal blood pressure decline, the so called 'dipping' blood pressure pattern. DESIGN AND METHODS: A total of 12 patients with APA and 36 patients with EHT who were matched by age and sex, and who had no severe organic disorders, were hospitalized to control their diet (low sodium) and activities. Ambulatory blood pressure monitoring was conducted for 24 h. The 24-h blood pressure was divided into waking blood pressure (0600-2130 h) and sleeping blood pressure (2200-0530 h). RESULTS: The two groups showed no significant differences in age, sex, serum creatinine, plasma glucose, daily urinary sodium excretion, and left ventricular mass index. Although the 24-h mean blood pressure was higher in APA (112 +/- 8 mmHg) than EHT (102 +/- 12 mmHg), the dipping mean blood pressure ratio (%), which was calculated from the sleeping and waking blood pressures, did not differ significantly between the two groups (93.2 +/- 5.4 versus 92.8 +/- 5.9). CONCLUSION: The dipping ratio of blood pressure in patients with APA resembled that of patients with EHT. Variables that would influence the circadian rhythm of blood pressure were controlled during study. The results suggest that a circadian blood pressure in patients with APA is of the dipping type, characterized by a nocturnal blood pressure decline, when a low sodium diet is ingested.     

血钾正常的原发性醛固酮增多症患者临床特点分析

目的分析血钾正常的原发性醛固酮增多症患者的临床特点。方法选择2013-01~2016-12在东莞市中医院确诊的140例原发性醛固酮增多症患者,将其分为低血钾组60例和正常血钾组80例,回顾性分析其临床、生化及影像学资料。结果低血钾组以1级高血压和2级高血压多见,而正常血钾组以2级高血压和3级高血压多见(P 0. 05)。低血钾组血钠[(149. 79±4. 23) mmol/L]高于正常血钾组[(140. 23±2. 86) mmol/L],差异有统计学意义(P 0. 05),而低血钾组血钾[(2. 97±0. 2) mmol/L]低于正常血钾组[(3. 92±0. 3) mmol/L],差异有统计学意义(P 0. 05)。两组患者的坐位肾素活性、坐位醛固酮水平比较差异无统计学意义(P 0. 05)。低血钾组中醛固酮瘤多见,而正常血钾组中特发性醛固酮增多症更为多见,两组患者的肾上腺病变差异有统计学意义(P 0. 05)。两组患者的左心室肥厚、颈动脉斑块、慢性肾功能不全、脑梗死等靶器官损伤情况比较差异无统计学意义(P 0. 05)。结论血钾正常的原发性醛固酮增多症患者临床表现不一,主要表现为中、重度高血压,其分型以特发性醛固酮增多症为主。     

Analysis of unilateral adrenal hyperplasia with primary aldosteronism from the aspect of messenger ribonucleic acid expression for steroidogenic enzymes: a comparative study with adrenal cortices adhering to aldosterone-producing adenoma

Unilateral adrenal hyperplasia with primary aldosteronism is very rare and shows similar endocrine features to aldosterone-producing adenoma and bilateral adrenal hyperplasia. In this study, the mRNA expression of steroidogenic enzymes in unilateral adrenal hyperplasia was examined by in situ hybridization. We found subcapsular micronodules composed of spironolactone body-containing cells, which showed intense expression for 3beta-hydroxysteroid dehydrogenase, 11beta-hydroxylase, 18-hydroxylase, and 21-hydroxylase but not 17alpha-hydroxylase, indicating aldosterone production. This expression pattern was the same as that in unilateral multiple adrenocortical micronodules, reported recently. Additionally, it was noted that a nodule with active aldosterone production was closely adjacent to one showing intense 17alpha-hydroxylase expression. In the adrenal cortices adhering to aldosterone-producing adenoma, the majority of hyperplastic zona glomerulosa and hyperplastic nodules demonstrated a decreased steroidogenic activity. However, minute nodules indicative of active aldosterone production were found at high frequency. These results suggest that the subcapsular micronodules observed might be the root of aldosterone-producing adenoma. Furthermore, we emphasize the need for long-term follow-up after unilateral adrenalectomy or enucleation of the adenoma because of the possibility that buds with autonomous aldosterone production may still be present in the contralateral or remaining adrenal tissue.     

Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma

OBJECTIVE: To assess blood pressure outcome in patients with primary aldosteronism, who were operated on the basis of a unilateral adenoma detected by computed tomography or a lateralized aldosterone hypersecretion detected by adrenal venous sampling, and to analyze the hormonal and nonhormonal factors associated with the outcome. METHODS: A retrospective study of 168 patients with primary aldosteronism undergoing surgery: 109 patients with a unilateral adenoma detected by computed tomography and 59 without a unilateral adenoma who underwent surgery because of an aldosterone to cortisol ratio at least five times higher on the dominant side than on the nondominant side. RESULTS: Patients with a unilateral adenoma were more likely to be women, had a shorter history of hypertension and had lower blood pressure levels and treatment scores than patients without a unilateral adenoma. The mean systolic blood pressures of patients with and without unilateral adenomas at follow-up were 133 +/- 16 and 137 +/- 16 mmHg, respectively. Hypertension cure or improvement was observed in 77% (95% confidence interval 69-85%) and 68% (95% confidence interval 56-80%) of patients, respectively. Using a linear regression model, baseline urinary aldosterone was positively associated, and baseline serum potassium was negatively associated, with decrease in systolic blood pressure. CONCLUSION: Adrenalectomy improves blood pressure control in patients with primary aldosteronism operated on the basis of either unilateral adenoma detected by computed tomography or a lateralized aldosterone hypersecretion. A high urinary aldosterone excretion and a low serum potassium level predict a more favorable outcome of surgery.     

原发性醛固酮增多症58例症状分析

目的:通过回顾58例确诊为原发性醛固酮增多症(PA)患者的主要症状,提高对该病的认识;并评价这些症状对PA的诊断意义。方法:回顾性分析58例PA患者的主要症状包括高血压、低钾血症等;总结其在这些患者中的发生情况。结果:全部患者伴有高血压,以高血压为首发症状的患者占96.6%,其中1级高血压12例(20.7%),2级33例(56.9%),3级13例(22.4%);伴肌无力、乏力或肌麻痹的占53.4%。48例(83%)有低血钾,平均血钾浓度为(2.84±0.49)mmol/L,24h尿钾排泄[(51.90±38.0)mmol/L],增高者(25 mmol/24h)占95%;血钠增高(145 mmol/L)者占48.3%。结论:原发性醛固酮增多症患者一般均有高血压并低血钾,对于有高血压并低血钾者应高度怀疑原发性醛固酮增多症,作进一步特殊检查,早日确诊。     

Misdiagnosis of two cases of primary aldosteronism owing to failure of computed tomography to detect adrenal microadenoma

Recent studies have suggested that primary aldosteronism (PA) is a common form of hypertension. However, some cases of PA are overlooked because microadenoma is difficult to detect by imaging. The author report 2 cases in which aldosterone-producing microadenoma was diagnosed by selective adrenal venous sampling (AVS) and furosemide plus upright test. These adenomas were resected by laparoscopic adrenalectomy. Both cases presented with hypertension and hypokalemia. Experimental data, including those obtained from furosemide plus upright test, suggested PA. In both cases, computed tomography imaging revealed a normal adrenal gland without any tumor. However, selective AVS indicated unilateral hypersecretion of aldosterone. Laparoscopic adrenalectomy was performed, and clinical symptoms of the patients improved. The histopathologic findings revealed aldosterone-producing microadenomas with diameters of 6 and 3 mm, respectively, in cases 1 and 2. In conclusion, AVS should be performed to confirm the diagnosis of PA when computed tomography imaging does not provide definite results.     

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

Summary Conclusion Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). Background We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. Methods Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. Results The urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d). The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.     

The role of endogenous dopamine on mineralocorticoids secretion in normal subjects, patients with primary aldosteronism, and idiopathic hyperaldosteronism

The role of endogenous dopamine (DA) on the secretion of several mineralocorticoids was studied in six normal subjects, eight patients with primary aldosteronism (PA), two patients with non-familial idiopathic hyperaldosteronism (NF-IHA), and four patients with familial IHA (F-IHA). To these subjects 10 mg metoclopramide (MCP) was administered intravenously, and plasma aldosterone (Ald), 18-OH-corticosterone (18-OH-B), 18-OH-11-deoxycorticosterone (18-OH-DOC), and DOC were measured by RIA. Further, five normal subjects were studied with MCP test after pretreatment with DA infusion (5 micrograms/kg/min over 90 min). After the administration of MCP, normal subjects showed significant increases in their plasma Ald and 18-OH-B, and slight increases in plasma 18-OH-DOC and DOC. However, no significant changes were observed in plasma ACTH, cortisol, PRA, serum K, Na and Cl. In patients with PA and NF-IHA, plasma Ald and the three precursors were increased after the administration of MCP. Especially, marked increases in plasma 18-OH-DOC were seen in PA patients. In contrast, F-IHA patients showed increases in the above mineralocorticoids except 18-OH-B. Following DA infusion in normal subjects neither basal plasma Ald secretion nor the responsiveness to MCP were modified. These results suggest that endogenous DA plays an inhibitory role in the terminal stages of mineralocorticoids production in man. However, the degree of the dopaminergic inhibition might be different between normal subjects and the patients with mineralocorticoids excess, and among the three groups of aldosteronism mentioned above.