Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia

BACKGROUND: Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. AIM: To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. DESIGN: Retrospective record review. METHODS: From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. RESULTS: Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. DISCUSSION: Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.     

经手术病理证实的原发性醛固酮增多症102例临床分析

目的在经手术病理证实的原发性醛固酮增多症(PA)患者中评价术前各项诊断筛查方法的临床价值。方法回顾性分析经手术病理证实的102例PA患者的临床特征、生化资料及血浆醛固酮浓度(PAC)、血浆醛固酮与肾素比值(ARR),比较不同指标筛查PA的阳性率,不同试验对PA的确诊率及影像学检查对PA的检出率和诊断符合率。结果在上述患者中:(1)ARR>20 ng/dl·(ng·ml-1·h-1)-1筛查PA的阳性率为86.27%;ARR>20 ng/dl·(ng·ml-1·h-1)-1且PAC>15 ng/dl筛查PA的阳性率为68.63%(P<0.01)。(2)静脉盐水抑制试验和卡托普利抑制试验对PA的确诊率分别为100%和80%(P>0.05)。(3)影像学检查中,CT和MRI对PA的检出率明显高于超声(P<0.01);与术后病理对照,CT对醛固酮腺瘤(APA)和单侧肾上腺皮质增生(UAH)的诊断符合率分别为97.33%和78.26%(P<0.01),MRI对APA和UAH诊断符合率分别为88.89%和75.00%(P>0.05)。结论 ARR>20 ng/dl·(ng·ml-1·h-1)-1筛查PA的阳性率高于ARR>20 ng/dl·(ng·ml-1·h-1)-1联合PAC>15 ng/dl;盐水抑制试验和卡托普利抑制试验都有较高的确诊率;影像学检查中,CT对PA有较高的检出率和诊断符合率,对于分型而言,CT对APA的诊断符合率高于UAH。     

Primary aldosteronism

Primary aldosteronism is a potentially curable form of hypertension. Recent studies using the plasma aldosterone to plasma renin activity ratio as screening test in hypertensive populations have demonstrated a high prevalence of primary aldosteronism close to 10%. This frequency is clearly higher than the classically described when hypokalemia is used as the screening method. The most common subtypes of primary aldosteronism are idiopathic aldosteronism and aldosterone-producing adenoma. Other causes are glucocorticoid-remediable aldosteronism, unilateral or primary adrenal hyperplasia and adrenal carcinoma. The diagnosis of primary aldosteronism is advocated to confirm the autonomy of aldosterone secretion from the renin-angiotensin system and to differentiate the clinical subtypes of the disease. This article reviews the new data about prevalence, diagnosis criteria and describes the clinical, biochemical and genetic characteristics of the different subtypes of the disease. We also discuss the treatment, and the differential diagnosis with other hyper-mineralocorticoid states.     

Recent progress of diagnosis and treatment of primary aldosteronism

In primary aldosteronism, cardio-cerebro-renal complication is higher in cases diagnosed after 5 years of onset of hypertension than those diagnosed before 5 years. Moreover, prognosis of hypertension and renal function after unilateral adrenalectomy for aldosterone-producing microadenoma with short-term exposure of hypertension is better than those for CT-detectable aldosterone-producing adenoma with long standing hypertension. Therefore, we should accurately diagnose PA among newly-onset hypertensive patients by simultaneous measurement of aldosterone and renin, and treat patients with aldosterone-producing microadenoma, which has been sometimes misdiagnosed as essential hypertension for a long time, by unilateral adrenalectomy, based on the diagnosis of adrenal venous sampling.     

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.     

Activity of [des-Aspartyl1]-Angiotensin II in Primary Aldosteronism

This study describes the effects of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6+/-1 to 14+/-3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33+/-8 to 65+/-13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III.Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history.     

原发醛固酮增多症亚型实验室检验结果分析

目的分析原发醛固酮增多症不同亚型的实验室检查结果差异。方法 92例原发醛固酮增多症患者,依据术后组织病理结果分为肾上腺腺瘤组（76例）和肾上腺增生组（16例）,比较2组血钾、血钠、血醛固酮、肾素、血管紧张素Ⅱ和醛固酮肾素比值。结果增生组血钾水平（（3.78±0.38）mmol/L）高于腺瘤组（（3.34±0.66）mmol/L）（P〈0.05）,血钠、血醛固酮、肾素、血管紧张素Ⅱ及醛固酮肾素比值（（143.61±2.45）mmol/L、13.5（6.8,245.0）ng/（L·h）、（0.66±0.72）mg/L、（36.90±23.37）ng/L、170.0（7.7,9 450.0））与腺瘤组（（144.53±3.16）mmol/L、21.2（2.1,375.0）ng/（L·h）、（0.62±1.23）mg/L、（33.84±24.51）ng/L、111.0（2.1,6 820.0））比较差异无统计学意义（P〉0.05）。结论原发醛固酮增多症肾上腺腺瘤和肾上腺增生患者临床表现相似,术前检测血钾有助于亚型判定。     

Activation of aldosterone secretion in primary aldosteronism

Angiotensin infusion evokes marked increases in aldosterone secretion in primary aldosteronism and little change in secondary aldosteronism. The low plasma renin activity of primary aldosteronism and the elevated plasma renin activity of secondary aldosteronism are thought to account for this differential response. The effect of angiotensin on aldosterone and 18-hydroxycorticosterone secretion was studied during adrenal vein catheterization in seven patients with primary aldosteronism (whose plasma renin activity had been elevated following spironolactone therapy), one hypertensive patient with normal plasma renin activity and normal aldosterone secretion, two patients with secondary aldosteronism who had elevated plasma renin activity, and one anephric patient whose plasma renin activity was 0. Adrenal venous aldosterone and 18-hydroxycorticosterone were measured before and after a ten min sub-pressor angiotensin infusion.The cells of the aldosterone-producing adenoma (APA) respond to small increases in plasma angiotensin with large increases in secretion of aldosterone and 18-hydroxycorticosterone. The dose of angiotensin capable of evoking this response from the aldosterone-producing adenoma produces little or no change in the secretion of the steroids from nontumorous glands. The augmentation of aldosterone secretion, induced by angiotensin, in primary aldosteronism is due solely to increased secretion by the adenoma and not by the contralateral zona glomerulosa. The increased sensitivity of the aldosterone-producing adenoma is characteristic of the tumor. This response is independent of fluctuations in endogenous plasma renin activity. This sensitivity is not blunted by high plasma renin activity, nor is it a function of tumor mass for the effect is observed in aldosterone-producing adenomas regardless of size. ACTH injection after angiotensin infusion resulted in a marked increase in aldosterone concentration in the effluent from the nontumorous adrenal, but was not capable of producing further increases in aldosterone concentration in the effluent from the APA. In view of this exquisite sensitivity to infused angiotensin, it may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in aldosterone secretion in patients with aldosterone-producing adenomas.     

Converting enzyme inhibition with captopril in patients with primary hyperaldosteronism

The humoral and hemodynamic effects of converting enzyme inhibition captopril are presented in two patients with primary hyperaldosteronism (PHA). In all, 20 patients with resistant hypertension were treated with the angiotensin converting enzyme inhibitor captopril. In 18 patients with essential or renovascular hypertension mean (+/- SEM) plasma renin activity (PRA) rose from 5.0 +/- 1.4 to 35.3 +/- 5.3 ng/ml/hr (P less than 0.01) and mean (+/- SEM) plasma aldosterone (PA) declined from 25.8 +/- 2.9 to 15.1 +/- 1.9 ng/ml (P less than 0.01) after captopril. In two patients with PHA the PRA was not stimulated by converting enzyme inhibition, although there was modest decline in PA and a temporary reduction in blood pressure. After surgical removal of aldosterone-producing adenomas, PRA responsed appropriately to captopril. These cases illustrate that a disease process can modify the response to a drug and demonstrate that, in patients with PHA, captopril does not stimulate PRA, induces only minor decrements in PA, and is relatively ineffective as an antihypertensive.     

Primary aldosteronism: diagnosis and treatment

The syndrome of primary aldosteronism produces few signs or symptoms. The diagnosis should be suspected when either spontaneous hypokalemia or easily provoked hypokalemia is found in a patient with hypertension. Hypokalemia in association with inappropriate kaliuresis, low plasma renin activity, and a high plasma aldosterone concentration/plasma renin activity ratio are the findings on initial screening tests that should suggest primary aldosteronism. The diagnosis must be confirmed by demonstrating nonsuppressible aldosterone excretion in conjunction with normal cortisol excretion. The choice of therapy is based on distinguishing unilateral from bilateral adrenal disease. With a unilateral adrenal adenoma, surgical removal reverses the hypokalemia and frequently cures the hypertension. In most patients with bilateral adrenal hyperplasia who are treated surgically, however, hypertension persists; thus, the initial treatment in these patients should be pharmacologic.     

Multiple plasma steroid responses to graded ACTH infusions in patients with primary aldosteronism

We measured the simultaneous responses of eight plasma steroids to the infusion of alpha 1-24 ACTH at incremental rates of 12.5 to 200 mlU/30 min in seven patients with primary aldosteronism (five with adenomas, two with adrenal hyperplasia) and in 10 normal controls studied on regular sodium intakes and while supine. Patients with primary aldosteronism from adenomas had relatively higher concentrations (p less than 0.05) of aldosterone, 18 OH-B, corticosterone, and DOC than the two with hyperplasia and, save corticosterone, above the range of the normal controls. We found inconsistent differences in plasma progesterone, 17-hydroxyprogesterone, deoxycortisol, and cortisol. These findings suggest that the intermediate steps in aldosterone biosynthesis are hypersensitive to physiologic amounts of ACTH in patients with aldosterone-producing adenomas. Plasma levels of steroids distal to progesterone, i.e., DOC, corticosterone, 18 OH-B, and aldosterone, are relatively higher after small amounts of ACTH in patients with adenomas than in normal subjects or those with adrenal hyperplasia.     

Primary aldosteronism: a pictorial essay

Primary aldosteronism is defined as secondary hypertension accompanied by aldosterone hypersecretion that leads to suppressed plasma renin, hypokaremia and hypertension. Primary aldosteronism occurs in 3–15% of hypertensive patients and is commonly caused by aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA). APA is usually treated by adrenalectomy, whereas IHA is best managed medically. Therefore, it is important to distinguish between unilateral and bilateral disease. Computed tomography (CT) is used to differentiate the subtypes. Even when multidetector CT is used, the detection rate of APAs of 1 cm or less is lower than 60% for the following reasons: (a) aldosterone secretion does not depend on tumor size, (b) a tumor may exist without lipid-rich cells, and (c) non-functioning unilateral adenomas are not uncommon, especially in older patients. Adrenal venous sampling is the gold standard for the differentiation of unilateral from bilateral disease in patients with primary aldosteronism. It is important to compare the laterality of aldosterone secretion by performing simultaneous bilateral blood collection 15 min following adrenocorticotropic hormone stimulation. The value of (aldosterone/cortisol)_side/(aldosterone/cortisol)_{contralateral side} provides the best discrimination between patients with and without APA.     

Aldosterone suppression with dopamine infusion in low-renin hypertension.

A dopaminergic mechanism has been proposed to suppress aldosterone secretion. To assess the possibility that a defect in the dopaminergic mechanism might enhance aldosterone secretion in hypertensive patients, we determined basal and adrenocorticotropic hormone (ACTH)-stimulated plasma aldosterone (PA), cortisol, renin activity, and potassium concentrations before and during dopamine receptor stimulation with dopamine infusion and bromocriptine administration and dopamine receptor blockade with metoclopramide. The patient study groups included: (a) seven patients with low-renin hypertension and abnormal aldosterone suppression with sodium loading and presumed bilateral zona glomerulosa hyperplasia (ZGHP); (b) two patients with aldosterone-producing adenoma; (c) five patients with low-renin hypertension but normal aldosterone suppression with sodium loading; and (d) six patients with normal-renin hypertension. Dopamine infusion in patients with ZGHP caused PA to fall (P less than 0.01) into the normal range, but did not block the enhanced (P less than 0.05) aldosterone response to ACTH that is characteristic of these patients. Dopamine infusion in patients with low-renin hypertension but normal aldosterone suppression also suppressed PA (P less than 0.01), whereas it had no effect upon PA in patients with normal-renin hypertension or aldosterone-producing adenoma and did not blunt the PA response to ACTH in either group. Bromocriptine administration had no effect upon basal or ACTH-stimulated PA. Dopamine infusion in patients with ZGHP also enhanced (P less than 0.05) diuresis and natriuresis in comparison with normal-renin patients. Metoclopramide administration increased (P less than 0.01) PA in all patients. Thus, a dopaminergic mechanism appears to be important in the regulation of aldosterone secretion in patients with ZGHP and in other low-renin hypertensives with normal aldosterone suppression with sodium loading. In contrast, this latter group does not exhibit an enhanced aldosterone response to ACTH. Both of these groups differ from normal-renin hypertensives, who have no PA suppression with dopamine infusion.     

肾上腺静脉取血分型定位原发性醛固酮增多症的护理措施

目的探讨经导管行肾上腺静脉取血（adrenal venoussampling，AVS）分型定位原发性醛固酮增多症（primaryaldosteronism，PA）的护理要点。方法利用股静脉导管插管对46例PA患者行AVS检查，测定肾上腺分泌功能。结果（1）46例PA患者中43例双侧AVS成功，成功率为93％；22例提示为醛固酮瘤，21例提示为双侧肾上腺增生。（2）检查过程中，45例患者能配合AVS检查；1例因过分紧张、血压升高而取消检查，38例患者主诉紧张，30％的患者术后自觉双侧或单侧腰痛。结论做好心理护理及术中配合，加强术后并发症的观察和预防，是确保AVS成功率和准确性的关键。     

Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study.

BACKGROUND: Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH). However, it is still unknown whether reduced myocardial perfusion at rest and/or regional function abnormalities are present during exercise-induced myocardial stress. PURPOSE: We addressed the impact of PA on myocardial ischemia and sought to identify signs of exercise-induced myocardial ischemia (assessed by MIBI-SPECT and echocardiography) in patients with PA compared to patients with EH. Patients with consistent signs of myocardial ischemia on all of the tests were studied by coronary arteriography. PATIENTS: We studied 72 patients with PA and an age/sex-matched group of 72 patients with EH enrolled in the cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study (PAHIMS). METHODS: Regional function was detected from echocardiographic measurement of wall motion done at baseline and immediately after exercise. Myocardial perfusion was evaluated by SPECT imaging after injecting 99mTc-MIBI with the same-day protocol using the rest-stress sequence. RESULTS: Although the conditions of arterial pressure, duration of hypertension, and target organ damage were equivalent, the patients with PA had greater incidence of both reversible perfusion defects and abnormalities of regional function. Moreover, multiple regression analysis showed that the high plasma aldosterone level was highly predictive for SPECT ischemic score and wall motion index, suggesting that PA contributes to cardiovascular risk over and above that associated with ventricular hypertrophy. Exercise-induced myocardial ischemia in PA was not segmental but widely distributed suggesting that this phenomenon was not related to abnormal coronary perfusion. Accordingly, of the 38 patients with PA who underwent coronarography, there was no presence of significant coronary atherosclerotic lesions in 30 (78.9%) of the patients. CONCLUSIONS: The PAHIMS observed more exercise-induced moderate myocardial ischemic defects (co-detected by SPECT and echocardiograms and not segmental but widely allocated) in patients with PA than in patients with EH. This phenomenon occurred in a greater percentage of patients with PA without significant coronary lesions (78.95%, n = 38), which supports the possible presence of small-vessel intramyocardial disease.     

原发性醛固酮增多症合并亚临床型皮质醇增多症临床特点及其发病机制探讨

目的探讨原发性醛固酮增多症合并亚临床型皮质醇增多症（即醛固酮/皮质醇共分泌瘤）的临床特点及其可能的发病机制,提高醛固酮/皮质醇共分泌瘤的诊治水平。方法回顾分析13例临床诊断为原发性醛固酮增多症（其中单纯性醛固酮腺瘤8例,合并亚临床型皮质醇增多症5例）的临床资料。通过免疫组化及RT-PCR检测腺瘤及瘤旁组织类固醇合成限速酶编码基因（CYP11B1和CYP11B2）的表达情况。结果醛固酮/皮质醇共分泌瘤的最大直径[（3.48±1.51）cm]大于单纯醛固酮腺瘤[（1.61±0.36）cm],差异具有统计学意义（t=-3.412,P=0.006）;醛固酮/皮质醇共分泌瘤患者血钾水平[（4.00±0.29）mmol/L]高于单纯醛固酮腺瘤[（3.15±0.72）mmol/L],差异具有统计学意义（t=-2.460,P=0.032）。结论原发性醛固酮增多症合并亚临床型皮质醇增多症并不少见,其具有独特的临床特点。     

正常血压型原发性醛固酮增多症的诊断学特征并文献复习

目的探讨正常血压型原发性醛固酮增多症(PA)的诊断学特征。 方法回顾性分析2018年5月4日中山大学附属第三医院内分泌科收治的1例血压正常、低血钾的PA患者的临床资料，并进行文献复习。 结果患者女性，39岁，因"四肢乏力麻木3年余，加重2 d"入院，监测血压正常，实验室检查显示血钾2.10 mmol/L，血醛固酮水平升高(465.83 pmol/L)，肾素浓度偏低(2.90 ng/L)，CT提示右侧肾上腺皮质腺瘤(23 mm×18 mm)，确诊为PA。该患者整个病程未发现高血压。 结论对低血钾麻痹而无高血压的患者，要警惕正常血压型PA的可能，避免漏诊。     

Primary aldosteronism caused by aldosterone-producing adenoma in pregnancy--complicated by EPH gestosis

Pregnancy in conjunction with primary aldosteronism is an unusual occurrence. We report a 28-year-old woman who presented with mild hypertension and hypokalemia as manifestations of primary aldosteronism caused by an aldosterone-producing adenoma in the left adrenal gland during pregnancy. Although the diagnosis was straightforward, the patient refused to undergo the proposed operation during the second trimester of her pregnancy. She was not admitted to hospital until she developed EPH gestosis in the 27th week of gestation, which had an unfavourable outcome for the infant who died nine days after delivery. The patient underwent a laparoscopic adrenalectomy which resulted in normalization of blood pressure and blood potassium levels. In cases of aldosterone-producing adenoma, surgery in the second trimester is the most appropriate option to avoid a poor obstetric outcome.     

Primary aldosteronism in childhood due to primary adrenal hyperplasia

We present an unusual case of primary aldosteronism in childhood. A 9-year-old boy had hypertension, hypokalemia, hyporeninemia and hyperaldosteronism. Dexamethasone administration decreased plasma aldosterone transiently but failed to correct the hyperaldosteronism, excluding dexamethasone-suppressible hyperaldosteronism. Plasma aldosterone decreased with upright posture and showed a circadian rhythm. Spironolactone treatment normalized blood pressure and serum potassium and lowered aldosterone secretion. During the studies, plasma aldosterone correlated with serum cortisol but not with plasma renin. Preoperative results indicated that this patient presented the functional features of aldosteronoma. Adrenal computed tomography, scintigraphy and left venography were not diagnostic of adrenal lesions. The left adrenal venous sampling showed hypersecretion of aldosterone from the left adrenal gland. The left adrenalectomy revealed micronodular hyperplasia but resulted in a prompt and sustained reversal of hypertension and hyperaldosteronism. These findings suggest that primary aldosteronism in this patient resulted from primary adrenal hyperplasia. Thus, adrenal hyperplasia is a heterogenous group of disorders and carefully selected studies allow prospective selection of appropriate treatment.     

The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism.

The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus.