Low-renin ("primary") hyperaldosteronism. Differential diagnosis and distinction of sub-groups within the syndrome.

Hypokalemia in a hypertensive patient is commonly diuretic-induced. However, if hypokalemia persists after stopping diuretic therapy, possible mineralocorticoid excess, including primary hyperaldosteronism, must be considered. Hypertension with secondary hyperaldosteronism may occur with malignant-phase hypertension and with renal or renovascular disease. However, secondary hyperaldosteronism is associated with raised circulating levels of renin and angiotensin II, while in primary hyperaldosteronism plasma concentrations of renin and angiotensin II are inappropriately low.Hypertension and hypokalemia may also be associated with an excess of a mineralocorticoid other than aldosterone. Syndromes associated with an apparently isolated excess of 11-deoxycorticosterone, of 18-hydroxy-11-deoxycorticosterone and of corticosterone have been described. Plasma renin may be suppressed as in primary hyperaldosteronism, but aldosterone values are normal or low. Hypertension, hypokalemia, and renin suppression may also occur in Cushing's syndrome, associated with abnormalities of corticosteroid synthesis and during ingestion of licorice-containing drugs. Again, aldosterone values are normal or low.Once the diagnosis of primary hyperaldosteronism has been confirmed, the rare cases of glucocorticoid-remediable hyperaldosteronism and hyperaldosteronism associated with adrenal or ovarian carcinoma must be excluded. There-after, it is necessary to distinguish between the two commonest forms, a unilateral adrenocortical adenoma and bilateral hyperplasia of the zona glomerulosa. The statistical technique of quadric analysis used prospectively has correctly predicted adrenal pathology in 23 of 24 patients. Other methods for differentiating the two groups include comparisons of aldosterone response to sodium loading, comparison of postural and diurnal changes in plasma aldosterone, adrenal venography, and examination of the adrenal glands by ultrasound and by scintillation scanning.     

The treatment of low-renin ("primary") hyperaldosteronism

Sixty-four patients with low-renin (“primary”) hyperaldosteronism underwent adrenal surgery. A unilateral adrenocortical adenoma was found in 48; no tumor was identified in 14, the adrenal glands then usually showing hyperplasia of the zona glomerulosa. The adrenal lesion in two further patients was difficult to classify. There was a significant fall in systolic and diastolic blood pressure after operation in both the adenoma and hyperplasia groups, although the fall in diastolic pressure was significantly greater in the adenoma group. Blood pressure fell to an arbitrary normal level in 56 per cent of patients with adenoma and in 15 per cent of patients in the hyperplasia group.Ninety-five patients with primary hyperaldosteronism received spironolactone for a minimum period of four weeks. There was a significant fall in mean systolic and diastolic pressure during treatment in both the adenoma and hyperplasia groups. However, the fall in diastolic pressure was again significantly greater in the adenoma group. There was a significant positive correlation between the fall in blood pressure during spironolactone and following adrenal surgery.Eighteen patients also received amiloride preoperatively and again there was a significant fall in systolic and diastolic blood pressure, although levels were slightly higher than during spironolactone or after subsequent adrenal surgery. Nineteen patients received a two week course of dexamethasone, without effect on blood pressure or the electrolyte abnormalities.It is suggested that removal of the tumor-bearing gland is usually the treatment of choice for patients with an aldosterone producing adenoma, provided preoperative spironolactone has reduced blood pressure to normal or near normal. However, long-term spironolactone is an acceptable alternative. For patients in the hyperplasia group, long-term spironolactone is usually the treatment of choice. If this drug is not tolerated, amiloride may be substituted. If preoperative spironolactone does not produce a satisfactory hypotensive response, adrenal surgery is unlikely to do so and hypertension should be controlled with other conventional hypotensive drugs. All patients with primary hyperaldosteronism in whom an adrenocortical adenoma is not identified preoperatively should be screened for the rare glucocorticoid-remediable variant. Dexamethasone 1 to 2 mg. daily for two to four weeks will reverse the biochemical abnormalities and reduce blood pressure. When an adrenocortical carcinoma is suspected, prompt surgical excision is required.     

The Mineralocorticoid Hormone Pathways in Hypertension with Hyperaldosteronism

Simultaneous measurement of the 0800-hr plasma concentrations of deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycortico-sterone (18-OHB), aldosterone, 18-hydroxydeoxycorticosterone (18-OHDOC) and cortisol (F) in four types of primary aldosteronism provides evidence for primary adrenal disease. Elevated DOC with normal F concentrations in the presence of elevated 18-OHB and aldosterone, and suppressed renin concentration suggests a primary adrenal abnormality of the zona glomerulosa (ZG). Steroid production by the zona fasciculata (ZF), F, 18-OHDOC, and most often B, is normal. These patterns exist only for primary adrenal hyperplasia, aldosterone-producing adenoma (APA), and aldosterone-producing adrenocortical carcinoma (AP-Ca). Elevated DOC levels are rarely found in patients with idiopathic hyperaldosteronism (IHA or adrenal hyperplasia) and suggest that IHA is not a primary adrenal disorder and should be excluded from the syndrome of primary aldosteronism as they have been heretofore.     

18例肾上腺皮质嗜酸细胞腺瘤患者的临床特征

目的 探讨肾上腺皮质嗜酸细胞腺瘤临床特点,以提高临床认识.方法 回顾性分析本院1993年1月至2009年11月住院的586例肾上腺皮质腺瘤中术后病理证实为肾上腺皮质嗜酸细胞腺瘤的患者18例(男性7例,女性11例),年龄(45.5±15.9)岁,病程(13.3±13.1)个月.结果 18例肾上腺皮质嗜酸细胞腺瘤患者中皮质醇增多症6例,原发性醛固酮增多症2例,皮质醇增多症合并原发性醛固酮增多症1例,无功能瘤9例.术前误诊为嗜铬细胞瘤4例.18例患者均经肾上腺超声诊断,均行手术治疗,其中腹腔镜手术13例,开腹手术5例,左侧11例,右侧7例,肿瘤平均直径5.6 cm.术后病理支持肾上腺皮质嗜酸细胞腺瘤,其中存在恶性倾向5例,恶性1例,良性12例.随访11例,随访时间(20.5±20.1)个月,死亡2例,存活9例,复发1例.结论 肾上腺皮质嗜酸细胞腺瘤是一病理诊断,临床表现多样,肿物体积多较大,多数可行超声检查发现,但易被误诊.与以往报道不同,本组病例以内分泌功能异常居多.该病多数为良性,但恶性倾向明显,需密切随访.

Abstract：

Objective To explore the clinical features of adrenocortical oncocytoma for better understanding. Methods A total of 586 patients with adrenal cortical adenoma were retrospectively analyzed in our hospital from January 1993 to November 2009, in which 18 were diagnosed as adrenal cortical oncocytoma pathologically, with 7 male and 11 female, aged ( 45.5 ± 15.9 ) years, and the disease course of( 13.3 ± 13.1 )months. Results 6 patients suffered from Cushing's syndrome, 2 primary hyperaldosteronism, 1 had clinical features of both Cushing's syndrome and primary hyperaldosteronism, and 9 were nonfunctional. 4 cases were misdiagnosed as pheochromocytoma preoperatively. All 18 patients were diagnosed by B-mode ultrasound and operation ( 13 by laparoscopy, 5 by laparotomy). 11 tumors were located in the left adrenal while 7 in the right, with the average tumor size of 5.6 cm in diameter. Histopathologically, 1 was oncocytic adrenocortical carcinoma, while 17 were adrenocortical oncocytoma, in which 5 were potentially malignant and 12 were benign. 11 patients were followed up for 20.5±20.1 months. 2 patients were dead, and 9 were alive with tumor recurrence in 1 case. Conclusions Adrenocortical oncocytoma is a pathological diagnosis and the clinical manifestations are various. The tumors are usually large in size, and can easily be found by ultrasound, but may be wrongly diagnosed as pheochromocytoma. Being different from previous reports, the majority of these patients present with endocrine dysfunction. Most of these cases are benign, but malignant potential is obvious. Therefore,follow-up is very important.     

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.     

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.     

HYPERMINERALOCORTICOIDISM DUE TO ADRENAL CARCINOMA: PLASMA CORTICOSTEROIDS and THEIR RESPONSE TO ACTH and ANGIOTENSIN II

A 47-year-old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11-deoxycorticosterone and corticosterone in addition to aldosterone and 18-hydroxycorticosterone. Basal 11-deoxycorticosterone levels were particularly high. Corticosterone, 18-hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma cortisol and assays for sex hormones were normal although there was evidence that cortisol derived from the neoplasm. At operation a well-differentiated adrenocortical carcinoma weighing 50 g (56 X 30 X 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11-deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.     

ADRENOCORTICAL CARCINOMA PRESENTING AS PRIMARY ALDOSTERONISM IN A YOUNG MAN

A young Polynesian man presented with severe hypertension complicated by an intracerebral hemorrhage. The hypertension was found to be secondary to hyperaldosteronism from a well differentiated adrenocortical carcinoma. Surgical removal of the tumour has resulted in a near normal blood pressure with no evidence of tumour recurrence or hyperaldosteronism after one year.     

Steroid profile in an adrenocortical carcinoma producing aldosterone.

We report a rare case of primary aldosteronism due to an adrenocortical carcinoma. A 61-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 4.2 cm measuring adrenal mass without secondary signs of malignancy. Endocrinological testing was consistent with primary aldosteronism. The patient underwent surgical resection of the adrenal mass; histology revealed an adrenocortical carcinoma. Postoperatively blood pressure, serum potassium, and aldosterone returned to normal. Four months after adrenalectomy, the patient presented again with hypokalemic hypertension and was found to have metastatic disease. Endocrinological investigation revealed primary aldosteronism and subclinical autonomous glucocorticoid hypersecretion. Careful hormonal investigation should be obtained in patients with adrenal masses causing excessive aldosterone secretion. In uncertain cases of primary aldosteronism, we would suggest to measure 18-hydroxycortisol levels, as excessive amounts may indicate adrenocortical carcinoma.     

Human adrenocortical carcinoma cell lines

The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three distinct zones of the adrenal cortex. Disruption of adrenal steroid production results in a variety of diseases that can lead to hypertension, metabolic syndrome, infertility and androgen excess. The adrenal cortex is also a common site for the development of adenomas, and rarely the site for the development of carcinomas. The adenomas can lead to diseases associated with adrenal steroid excess, while the carcinomas are particularly aggressive and have a poor prognosis. In vitro cell culture models provide important tools to examine molecular and cellular mechanisms controlling both the normal and pathologic function of the adrenal cortex. Herein, we discuss currently available human adrenocortical carcinoma cell lines and their use as model systems for adrenal studies.     

Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1.

In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal cortex has been found in about one third of necropsy cases. To elucidate the clinical and genetic characteristics of the MEN-1 adrenal lesion, we have investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical carcinoma. The apparently benign adrenal enlargements were not associated with presently ascertainable biochemical disturbances in the hypothalamic-pituitary-adrenocortical axis, and they were without radiological signs of progression during follow-up. The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements. Pancreatic endocrine tumors were significantly overrepresented and present in all MEN-1 individuals with adrenal involvement. In agreement with findings in sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q 13. Despite its prevalence and malignant potential, the pituitary-independent adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but might represent a secondary phenomenon, perhaps related to the pancreatic endocrine tumor.     

Concurrent adrenocortical carcinoma and Conn's adenoma in a man with primary hyperaldosteronism. In vivo and in vitro studies.

This is a report of a rare and unusual case of adrenal pathology. A patient presented with clinical and biological signs of primary aldosteronism and computed body tomography scan led to our suspecting the presence of a left adrenocortical carcinoma. The in vitro studies performed on the resected tumour showed very low synthesis of mineralocorticoids and glucocorticoids. The patient could not be reexamined until 15 months later, when he still suffered hypertension; another tomography scan revealed a mass on the right adrenal gland. The studies performed on this second tumour confirmed the diagnosis of Conn's adenoma: active in vitro biosynthesis of 18-hydroxy-corticosterone and aldosterone from exogenous tritiated precursors.     

Adrenocortical carcinoma producing 11-deoxycorticosterone: a rare cause of mineralocorticoid hypertension

A 37-yr-old man presented with the classic signs of mineralocorticoid excess hypertension and hypokalemia. The cause was not aldosterone excess, but elevation of plasma 11-deoxycorticosterone (DOC). Computed tomography (CT) scans showed a large right adrenal mass without signs of metastatic disease. The tumor was removed by open laparotomy, and histology revealed an adrenocortical carcinoma. Two yr after diagnosis, the patient is in good general condition and there is no sign of recurrence or metastatic disease, despite the large tumor size. DOC producing adrenocortical carcinomas causing mineralocorticoid hypertension are very rare, so far only 10 cases have been described in the literature.     

Primary adrenal natural killer/T-cell nasal type lymphoma: first case report in adults

We report the first case of a primary adrenal natural killer (NK)/T-cell nasal type lymphoma in adults. The patient presented with an enlarging left adrenal mass and the initial concern was for adrenocortical carcinoma. Surgical resection revealed NK/T-cell lymphoma. Rapid recurrence in the contralateral adrenal gland was treated with a single cycle of chemotherapy before he died due to infectious complications and progressive disease. This case demonstrates the aggressive presentation of a novel subset of primary adrenal lymphoma that should be considered in the differential diagnosis of a rapidly enlarging adrenal mass.     

Pure primary hyperaldosteronism due to adrenal cortical carcinoma

A 47-year-old woman is described who had pure primary hyperaldosteronism due to an adrenal cortical carcinoma. This may represent the first such case in which modern laboratory tests allowed specific diagnosis and exclusion of hypersecretion of other adrenal steroids, and also the first reported case in which modern localizing procedures have been utilized. Other interesting facets of the case include calcification of the tumor, visualization with 131l iodomethylnorcholesterol , metaplastic histologic changes, and coexistent bilateral renal artery fibromuscular disease.     

The value of scintigraphy and computed tomography for the differential diagnosis of primary hyperaldosteronism

Adrenocortical adenoma is the most common cause of primary hyperaldosteronism. Most tumours are small, less than 2 cm in diameter and, therefore, their localization may be difficult. We have compared two different methods, adrenal scintigraphy (AS) and computed tomography (CT) in the differential diagnosis of 12 patients with primary hyperaldosteronism. AS was performed using either [131I]cholesterol or 6-iodomethyl-19-norcholesterol during dexamethasone suppression. Of the patients, five showed a normal CT and symmetrical uptake of the isotope as AS. They were considered representative of bilateral hyperplasia. All showed good therapeutic response to spironolactone. Seven patients had an adrenocortical adenoma verified at operation. The CT finding indicated a tumour in five patients. This was correct in four, but in one patient the adenoma was found in the contralateral adrenal gland. In two patients with an adenoma, CT was considered normal. AS correctly indicated the tumour in all seven patients. The uptake was unilateral in six, and bilateral but clearly asymmetrical in one patient. The results indicate that AS is superior to CT in the pre-operative localization of aldosteroma. Although CT remains the primary method for the investigation of these patients, AS should be applied always when CT does not unequivocally indicate the presence and localization of an adrenal tumour.     

Collision/composite tumors of the adrenal gland: a pitfall of scintigraphy imaging and hormone assays in the detection of adrenal metastasis

CONTEXT: In patients with a history of extraadrenal tumor, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy. Detection of the malignant tissue is a difficult challenge when metastasis occurs in an adrenal adenoma, forming a collision/composite tumor. OBJECTIVE, DESIGN, AND SETTING: We report two patients with adrenal collision/composite tumors referred to two French university hospitals. PATIENTS AND RESULTS: Two patients with histories of mammary and sigmoid carcinomas, respectively, presented with adrenal mass discovered 8 and 3 yr after surgical removal of the primary tumor. In the two cases, computerized tomographic scan showed that the adrenal tumor contained two components with low and high attenuation values, respectively. Uptake of iodocholesterol by the adrenal tumor in case 1 and elevated plasma ACTH-stimulated 17-hydroxyprogesterone values in case 2 strongly argued for the diagnosis of primary adrenocortical tumors. Enlargement of the adrenal mass during follow-up in case 1 and association of the adrenal lesion with a hepatic mass in case 2 led to adrenalectomy. In both cases, histological examination of the tumor demonstrated the presence of metastatic carcinoma tissue in an adrenocortical adenoma, allowing classification of the neoplasia as a collision/composite tumor. CONCLUSION: These observations show that collision/composite tumors of the adrenal gland formed by carcinoma metastasis in benign adenomas are a pitfall of iodocholesterol scintigraphy and/or plasma steroid assays to exclude the diagnosis of adrenal metastasis. Conversely, computerized tomographic scan is a useful tool for the distinction between the benign and malignant tissues in adrenal collision/composite tumors.     

Adrenocortical carcinoma manifesting pure primary aldosteronism: a case report and analysis of steroidogenic enzymes

Adrenocortical carcinoma manifesting pure hyperaldosteronism is extremely rare. We report here a 61-year-old woman with biochemically proven primary aldosteronism due to right adrenocortical carcinoma. Computed tomographic scan showed 4.5x5.3 cm lobulated mass with tiny calcification, while there was no significant uptake of 131I-iodomethyl norcholesterol in the tumor. Immunohistochemical analysis demonstrated expression of steroidogenic enzymes in the tumor tissue: P-450scc, P-45c21, 3beta-hydroxysteroid dehydrogenase, P450(17alpha), and P-450(11beta). In addition, we could demonstrate mRNA expression of aldosterone synthase (P-450aldo:CYP11B2) in the tumor by specific ribonuclease protection assay. This is the first report of a case of primary aldosteronism due to adrenocortical carcinoma, in which expression of all sets of steroidogenic enzymes required for aldosterone synthesis was proven.     

Hypersecretion of a New Corticosteroid, 18–Hydroxycortisol in Two Types of Adrenocortical Hypertension

The most abundant substance in the urinary free steroid fraction of patients with primary aldosteronism has been identified as 18–hydroxycortisol. 18–hydroxycortisol is very likely an adrenocortical secretory product rather than a peripheral metabolite, since it is abundantly synthesized by aldosteronoma tissue slices. The biogenesis of 18–hydroxycortisol takes place from cortisol rather than from 18–hydroxy-corticosterone; that is, 17α-precedes 18–hydroxylation. Cortisol 18–hydroxylation appears to be unrelated to the two other types of adrenocortical hydroxylation at this position. The pathway is present to a small extent in the normal human adrenal cortex and is only moderately stimulated by ACTH. Cortisol 18–hydroxylation is markedly accentuated in two circumstances: in the aldosteronoma cell where its presence may serve to distinguish tumor from bilateral hyperplasia and in ACTH-stimulatable hyperaldosteronism where it represents the first qualitative steroid biochemical abnormality to be demonstrated and as such may be useful in diagnosis and genetic studies. The possible contribution of 18–hydroxycortisol to the severity of the clinical manifestations of mineralocorticoid excess in these two types of aldosteronism remains to be explored.     

Clinical, biochemical and pathological features of low-renin ("primary") hyperaldosteronism

The clinical and biochemical findings in 136 patients with low-renin (“primary”) hyperaldosteronism are described. A pathological diagnosis was made in 82 cases and a unilateral adrenocortical adenoma was found in 62. However, a tumor was not identified in 17, the adrenal glands then usually showing hyperplasia of the zona glomerulosa, often with nodular changes. The adrenal lesion in a further three cases proved fifficult to classify.Patients with an adrenocortical adenoma were significantly younger than those in whom a tumor was not found. The female/male ratio was greater than 2:1 in the adenoma group, but no sex difference was observed in the group without tumor. Vascular complications of hypertension occurred in 23 per cent and there was histologic evidence of malignant-phase hypertension in four. It is concluded that this condition is not a benign form of hypertension.Biochemical abnormalities were more marked among patients with an adrenocortical adenoma, compared with those in whom a tumor was not found. Mean plasma concentrations of aldosterone, sodium and tCO₂, and mean exchangeable sodium were significantly higher, while plasma potassium and renin concentrations and mean exchangeable potassium were significantly lower. Although plasma aldosterone was above normal at least once in all, levels were often only intermittently raised. Hypokalemia occurred in all patients with a proved adenoma and was usually persistent. Among patients in whom a tumor was not found, hypokalemia was less severe and usually intermittent, while plasma potassium was persistently normal in three of 17 patients in this group.In addition to the aldosterone excess, plasma deoxycorticosterone was raised in 13 of 26 patients, plasma corticosterone was marginally raised in two and plasma 18-OH-DOC in four of 15. There was a significant inverse correlation between plasma renin concentration and age in the non-adenoma group but not among patients with an aldosterone-producing adenoma. Weak positive correlations were observed in the adenoma group between total exchangeable sodium and both systolic and diastolic blood pressure and between exchangeable sodium and plasma aldosterone concentrations. Such correlations were not seen in the non-tumor group. The hypertension may have a different basis in these two groups.