Adrenal Aldosterone-producing Adenoma Research Articles

Does the captopril test improve the diagnosis of primary hyperaldosteronism?

Plasma concentrations of renin and aldosterone were measured before and 60 min after taking 25 mg captopril in 242 patients with arterial hypertension (124 men, 118 women, aged 51.9 +/- 12.7 years; unilateral aldosterone-producing adrenal adenoma in 8, idiopathic hyperaldosteronism in 16 and essential hypertension in 189). Basal plasma aldosterone levels were twice as high in those with adenoma or hyperaldosteronism (216.9 +/- 99.1 pg/ml and 256 +/- 123 pg/ml, respectively) as in those with essential hypertension (117.7 +/- 115 pg/ml). Basal renin levels in adenoma and idiopathic hyperaldosteronism (1 +/- 0.8 microU/ml and 2.6 +/- 1.9 microU/ml, respectively) were decreased compared with those in essential hypertension (13.1 +/- 14.2 microU/ml). The basal aldosterone/renin ratio was higher in adenoma (436 +/- 370 pg/microU) and idiopathic hyperaldosteronism (615 +/- 950 pg/microU) than in essential hypertension (52.9 +/- 151.3 pg/microU). The sensitivity of this ratio in combination with the aldosterone concentration was 100% for recognizing an adrenal adenoma, its specificity 92.7%. The mean plasma aldosterone level after captopril administration did not change in adenoma patients, but fell to 162 +/- 85 pg/ml (P less than 0.001) in those with idiopathic hyperaldosteronism. These data indicate that the captopril test contributes to distinguishing primary from idiopathic hyperaldosteronism.

A Case of Primary Aldosteronism Associated with Renal Artery Stenosis and Preclinical Cushing's Syndrome

We identified a left adrenal tumor, left renal atrophy, and left renal artery stenosis (RAS) in a 52-year-old man by MRI/magnetic resonance angiography (MRA) during evaluation of hypertension. Laboratory tests revealed hypokalemia, a high plasma aldosterone concentration (PAC), low plasma renin activity (PRA), and normal plasma cortisol. An excessive response of aldosterone and cortisol to adorenocorticotrophic hormone (ACTH) was found upon selective sampling of the left adrenal vein. Selective renal venous sampling showed a left/right renal venous PRA ratio of 1.7. A dexamethasone (8 mg) suppression test showed insufficient suppression of cortisol. We diagnosed this patient as having aldosterone-producing adrenal adenoma (APA) associated with renovascular hypertension (RVH) and preclinical Cushing's syndrome. As an initial treatment, percutaneous transluminal renal angioplasty was performed. Postoperatively, the patient's blood pressure decreased. One month later, the tumor was removed by complete laparoscopic left adrenalectomy. Postoperatively, blood pressure decreased further and both PAC and PRA were normalized. However, antihypertensive therapy could not be completely stopped. The renal dysfuntion that occurred prior to treatment seemed to prevent complete normalization of blood pressure.

Detecting and Treating Primary Aldosteronism

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies, using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-producing adrenal adenoma (APA), are the leading causes of primary aldosteronism. Glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, familial hyperaldosteronism type II and carcinomas are rare causes of PA. Patients with hypertension and hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with medication-resistant hypertension should be screened for PA using the PAC/PRA ratio. If a high ratio is found, a sodium loading test or a captopril test is warranted to confirm the diagnosis. Adrenal gland imaging is important in subtype differentiation (APA vs IHA). Adrenal venous sampling should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA. Surgery is considered the treatment of choice for patients with APA, while bilateral hyperplasia subtypes are treated medically. Normalization of aldosterone levels or aldosterone receptor blockade are necessary to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage.

Screening for primary aldosteronism

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.

Elevated Expression of Luteinizing Hormone Receptor in Aldosterone-Producing Adenomas

The mechanisms driving steroid production in aldosterone-producing adenomas (APAs) are poorly defined. However, previous studies have shown that steroid production in some cortisol-producing adenomas is regulated by aberrant expression of G protein-coupled receptors. Aberrant adrenal expression of LH receptors has been shown to cause Cushing's syndrome, but the role of LH receptors in Conn's disease (hyperaldosteronism) has not been studied. The objective of the study was to determine whether APAs express elevated LH receptor, compared with normal adrenal (NA). Pools of RNA from NA and APAs were hybridized to oligonucleotide microarrays. Data were confirmed using real-time RT-PCR analysis of RNA derived from NA (n = 20) and APAs (n = 18). Aldosterone synthase transcription was studied in H295R adrenocortical cells transfected with an LH receptor expression construct and reporter constructs prepared from CYP11B2 5'-flanking DNA. The patient population consisted of 20 normal control adrenals and 18 adenomas from patients with APAs. Regulation of CYP11B2 gene expression by aberrant LH receptor expression in aldosterone-producing adrenal adenoma was measured. LH/choriogonadotropin receptor gene and CYP11B2 are indicated as having greater than 25-fold expression in one pool of APA mRNA samples over NA using microarray analysis. Real-time RT-PCR analyses indicated that one APA sample (APA-LH receptor) exhibited more than 2400-fold elevation in LH receptor expression over NA. Examination of LH receptor mRNA levels in 18 independent APA samples indicated elevated expression in nine samples when compared with NA. In H295R cells transfected with LH receptor, LH treatment caused a concentration-dependent increase in CYP11B2 reporter activity. LH receptor expression is elevated in many APAs, which makes LH a potential cause of the excessive production of aldosterone in a subset of these adrenal tumors.

Comparison of adrenal vein sampling value between aldosterone producing adrenal adenoma and non-functioning adrenal adenoma: evaluation using receiver operating characteristic analysis

To evaluate adequate criteria for adrenal vein sampling values in patients with aldosterone producing adrenal adenoma (APA), retrospectively. Between 1988 and 2002, 59 hypertensive patients (15 M and 44 F, aged 47.58 +/- 9.45 years) were referred to our hospital and diagnosed with APA based on established criteria. During the same period, 23 patients with non-functioning adrenal adenoma (11 M and 12 F aged 53.56 +/- 11.76 years) were diagnosed based on computed tomography and laboratory data. All 82 patients were enrolled in the present study. Bilateral adrenal vein sampling (AVS) for measurement of plasma aldosterone (A) and cortisol (C) was performed, and a receiver operating characteristics (ROC) analysis was conducted to establish the best criteria from the AVS-derived index in patients with APA. A (APA side)/A (contralateral side) was confirmed to provide the best diagnostic accuracy {(>2.5: right APA, sensitivity 83.3%, specificity 79.5%), (> 3: left APA, sensitivity 84.2%, specificity 76.9)}. The Az values for A (APA side)/A (contralateral side) were 0.8948 and 0.9260 for right and left APA, respectively. The A (APA side)/A (contralateral side) value was the best compromise for sensitivity and false-positive rate for lateralization of APA.

Atrial and brain natriuretic peptides as markers of cardiac load and volume retention in primary aldosteronism

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones with natriuretic and vasodilator actions. The present study was carried out to determine the natriuretic peptide that is closely related to cardiac load and volume retention in patients with primary aldosteronism (PA). We examined 11 patients with PA due to aldosterone-producing adrenal adenoma before and after surgical resection. Plasma levels of ANP and BNP were measured by specific immunoradiometric assays, and total blood volume was determined by a plasma tracer method with (131)I-human albumin. Plasma levels of ANP and BNP were elevated in the PA patients compared with normotensive control subjects (P < .01), and the elevated ANP and BNP levels were reduced (P < .01) after adenoma resection. When analyzed with the pre- and postoperative data, a significant relationship was observed between mean blood pressure and plasma levels of ANP (r = 0.64, P < .01) and BNP (r = 0.58, P < .01). The BNP was significantly correlated with the SV1 + RV5 voltage (r = 0.65, P < .01) and with total blood volume (r = 0.57, P < .01), but this was not the case for ANP. The present results suggest that the plasma level of BNP is more closely related to cardiac load or volume status than ANP is, in patients with PA due to adrenal adenoma.

Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia

We report a case of an adenomatoid tumor (AT) of an adrenal gland with micronodular adrenal cortical hyperplasia (ACH). A 51-year-old man was found to have newly developed hypertension with clinical evidence of primary aldosteronism. A computerized tomogram of the abdomen revealed a solitary mass in the right adrenal gland. He underwent a right adrenalectomy for a presumptive clinical diagnosis of a solitary aldosterone-producing adrenal cortical adenoma. On histopathologic examination, the adrenal gland demonstrated an AT, diagnosed by the characteristic histological features, immunohistochemical stain results, and electron microscopic findings. The surrounding adrenal cortex showed multiple small hyperplastic cortical nodules. After the adrenalectomy, the patient’s blood pressure normalized. Primary AT of the adrenal gland coexisting with micronodular ACH associated with hypertension has not been previously reported.

Laparoscopic partial adrenalectomy in patients with aldosterone-producing adenomas: indications, technique, and results

Objectives To report the indications, technique, and results in patients with primary hyperaldosteronism due to aldosterone-producing adrenal adenoma treated by laparoscopic partial adrenalectomy. Laparoscopy has become the technique of choice in adrenal surgery, but adrenalectomy is the standard procedure. Only a few studies have reported on partial adrenalectomy, and the indications and technique have not yet been clearly defined. Methods From June 1995 to December 2001, 13 patients presented with hyperaldosteronism and a single adrenal adenoma (Conn’s syndrome) and were treated with laparoscopic partial adrenalectomy. The mean age was 60 years, and the average tumor size was 2.1 cm in diameter. A transperitoneal approach was used in all patients, tumors were resected with safety margins by endoshears, and hemostasis was achieved by bipolar coagulation and finally by sealing with fibrin glue. Results All procedures were finished laparoscopically, and no conversion was necessary. No major intraoperative or postoperative complication was observed. The histologic examination showed adenomas with negative surgical margins in all cases. Postoperative computed tomography revealed a normal blood supply for the remaining adrenal tissue. Blood pressure and aldosterone levels were unremarkable at follow-up, and no local recurrence was observed. Conclusions Laparoscopic partial adrenalectomy for aldosterone-producing adenomas is a minimally invasive procedure with a low complication rate. It provides the benefit of retaining functional tissue on the side of the affected adrenal gland. Therefore, we recommend laparoscopic partial adrenalectomy for patients with small, potentially benign, tumors of the adrenal gland, even with a healthy contralateral adrenal gland.

Hyperaldosteronism: The Internist’s Hypertensive Disease

Primary aldosteronism (PA) is a disorder typically characterized by resistant hypertension, hypokalemia, alkalosis and suppressed plasma renin activity, and excessive aldosterone production. A true estimate of the prevalence of the disorder is difficult to estimate because its detection is dependent on the awareness of the healthcare provider to the disorder, but it has generally been felt to be a rare occurrence. Its frequency of detection began to change when Hiramatsu suggested calculating the ratio of plasma aldosterone/plasma renin activity as a screening tool for the disorder. He found a ratio greater than 75 as a sensitive indicator for aldosterone-producing adenomas. Using the ratio, several investigators have found prevalence ranging from 3 to 9%. Two major classifications of PA exist: aldosterone-producing adrenal adenoma (APA) and zona glomerulosa hyperplasia (IHA). Distinguishing between these 2 entities is important clinically, because removal of a unilateral aldosterone-producing adenoma may result in correction of elevated blood pressure and hypokalemia. Thus, when evaluating hypertensive patients, PA should be suspected in those with moderate to severe hypertension or with hypertension refractory to standard treatment or in hypertensive patients with disease onset at an early age. The aldosterone-to-renin ratio is an easy, inexpensive, and rapid means of screening for the disorder. The ratio is the screening test of choice, but further confirmatory testing is required to clinch the diagnosis. Frequently employed confirmatory tests include urinary aldosterone excretion on a high-salt diet, aldosterone suppression after a saline infusion, and the fludrocortisone suppression test, which is considered the most sensitive confirmatory maneuver. Both high-resolution CT and MRI scans appear to have similar ability to differentiate between APA and IHA. As with essential hypertension, the goal of treatment is to prevent the long-term sequela of hypertension. The underlying pathology resulting in PA dictates the treatment strategy. The drug of choice is spironolactone. Surgical intervention should be entertained in those patients with PA in whom imaging studies suggest an adenoma.

肝細胞癌とホルモン産生副腎腺腫の重複腫瘍の1例

We report a rare case of coexisting hepatocellular carcinoma and aldosterone-producing adrenal gland adenoma. 64-year-old man admitted for acute myocardial infarction and angina pectoris was shown by laboratory data to have hypernatremia, hypokalemia, liver dysfunction, positive hepatitis C virus antibody and elevated PIVKA-II. Hormonal examination, standing shoulder and tolerance of angiotensin-converting enzyme inhibitor showed no responsive hyporeninemia or hyperaldosteronemia. Abdominal computed tomography showed an enhanced liver tumor in S8 and a left adrenal gland tumor. Abdominal angiography showed a tumor stain in S8 of the liver, and adrenal gland scintigraphy showed a hot tumor in the left adrenal gland. He was diagnosed with hepatocellular carcinoma with liver cirrhosis and aldosterone-producing adrenal gland adenoma. During medication for acute myocardial infarction and angina pectoris, we conducted transarterial embolization for hepatocellular carcinoma and drug control for Conn's syndrome. After heart function stabilized, he underwent hepatectomy of the anterior segment and left adrenalectomy. Resected specimens showed hepatocellular carcinoma and left adrenal gland adenoma. Liver cirrhosis was also recognized. It is important to think region of the adrenal gland caused by secondary aldosteronisms in hepatocellular carcinoma with liver cirrhosis.

A Case of Aldosterone-Producing Adrenocortical Adenoma Associated with Preclinical Cushing's Syndrome and Hypersecretion of Parathyroid Hormone.

A rare case of aldosterone-producing adrenocortical adenoma with preclinical Cushing's syndrome and hypersecretion of parathyroid hormone (PTH) is described. A 64-year-old male patient had a history of hypertension for two decades and hypokalemia for 4 years. He suffered from left hemiparesis and aphasia due to cerebral hemorrhage, but his appearance was not Cushingoid. His plasma renin activity was below the normal range, while plasma aldosterone concentration was high. They did not respond to furosemide-upright test. His plasma cortisol level in the morning was at the upper limit of the normal range, but it did not show a diurnal rhythm nor was it suppressed by 1 mg and 8 mg of dexamethasone. Computed tomography showed a low density tumor in the right adrenal gland. An adrenal scintigram under dexamethasone treatment revealed an uptake of the tracer on the right side, and plasma aldosterone and cortisol concentrations in the adrenal vein were higher on the right side than on the opposite. The diagnosis of right aldosterone-producing adrenal adenoma with an autonomous production of cortisol was confirmed by right adrenalectomy. Histological findings showed an adenoma consisting mostly of clear cells, but that the nests of compact cells were scattered. Analysis of an extract from the adenoma revealed that the adenoma contained an excess amount of aldosterone and that the cortisol/corticosterone ratio was higher than that of aldosterone-producing adenoma. Both serum calcium and PTH levels remained high one year after adrenalectomy. Ultrasonography revealed the swelling of a parathyroid gland on the left side, indicating the coexistence of an autonomous hyperparathyroidism.

Predictive Value of Preoperative Tests in Discriminating Bilateral Adrenal Hyperplasia from an Aldosterone-Producing Adrenal Adenoma

Predictive Value of Preoperative Tests in Discriminating Bilateral Adrenal Hyperplasia from an Aldosterone-Producing Adrenal Adenoma

Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore.

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

An assessment of diagnostic procedures preparatory to retroperitoneoscopic removal of adenoma in cases of primary hyperaldosteronism.

The goal of this study was to improve assessment of diagnostic measures for lateral localization of aldosterone-producing adrenal adenomas preparatory to retroperitoneoscopic removal, in view of the fact that this technique allows for only unilateral access. A retrospective study was carried out of the medical records of 64 patients (38 women, 26 men, average age 46.8+/-11.2) who underwent surgery at University Hospital, Münster, between 1969 and 1998. Seventeen of the 64 patients presented with hyperplasia and 47 had adrenal adenoma. In cases of hyperplasia, computerized tomography imaged a false-positive unilateral tumor 10 times, a false-negative 3 times, and a unilateral hyperplasia 1 time (ultrasonography: tumor 2 times, false-negative 3 times; 131I-Iodomethylnorcholesterol scintigraphy: tumor 5 times, false-negative 1 time, correct 1 time). In cases of adenoma, computerized tomography yielded accurate results 40 times, imaged a false-negative 2 times, and indicated the incorrect side 1 time (Ultrasonography: false-negative 12 times, correct side 9 times, incorrect side 1 time; 131I-Iodomethylnorcholesterol scintigraphy: correct side 19 times, false-positive (both sides) 5 times, negative 3 times, incorrect side 2 times). Venous sampling, which was carried out seven times, yielded accurate results six times, and failed technically one time. Venous sampling appears to be the method of choice for preoperative lateral localization. Thus, retroperitoneoscopic treatment of Conn's syndrome should not be carried out unless venous sampling is carried out first.

Renal pathology in patients with primary hyperaldosteronism secondary to an adrenal cortical adenoma

The cause of persistent hypertension following the removal of an aldosterone-producing adrenal adenoma is unknown. The purpose of this study was to determine whether this occurrence is due to existing renal histopathologic damage. Thirty-two patients with primary hyperaldosteronism due to an aldosterone-secreting adrenal cortical adenoma underwent open renal biopsy at the time of unilateral adrenalectomy. Biopsy results were correlated with the duration and severity of hypertension before and after surgery. Nineteen patients were cured of their hypertension postoperatively, whereas 13 patients had persistent diastolic hypertension. Statistical analysis of these two groups revealed no difference when renal histopathologic variables, preoperative severity of hypertension, or preoperative duration of hypertension were compared. Persistent hypertension in these patients does not appear to be due to renal histopathologic changes; coexisting essential hypertension is a more likely cause.

Calcified aldosterone-producing adrenocortical adenoma

We report the first case of benign aldosteronoma of an ordinary size with calcifications. We review the clinical, clinical imaging, histopathological, and laboratory features of aldosterone-producing adrenal adenoma versus carcinoma. We conclude that no single feature is diagnostic, and the full range of data must be considered. Calcifications may not necessarily be a distinguishing point.

Diagnosis and surgical treatment of primary aldosteronism in pregnancy: A case report

Aldosterone-producing adrenal adenomas are rare, especially during pregnancy. We report a patient who presented in the early second trimester, was diagnosed with primary aldosteronism, and was treated successfully by adrenalectomy. A 17-year-old black nulliparous woman was found to have a blood pressure (BP) of 150/82 mmHg when she registered for prenatal care at 14 weeks' gestation. Initial laboratory assessment revealed a markedly diminished serum potassium level of 2.1 mmol/L. Further laboratory evaluation detected decreased random plasma renin activity and an elevated aldosterone level. Magnetic resonance imaging revealed a 2-cm right adrenal lesion. She was diagnosed with an adrenal adenoma and successfully underwent an adrenalectomy at 17 weeks' gestation. Postoperatively, her BP and serum potassium level normalized. She spontaneously delivered a normal male infant at term. Although primary hyperaldosteronism is a rare clinical entity, it must be considered when hypertension and hypokalemia are present concurrently. Antepartum medical management can be difficult, often resulting in poor obstetric outcome. Surgery in the second trimester is an effective option.

Adjustment of the Osmostat in Primary Aldosteronism

To analyze osmoregulation in primary aldosteronism. The physiologic and pathologic factors involved in function of the osmostat and in hypernatremia were reviewed. Patients with primary aldosteronism commonly have mild hypernatremia, with serum sodium concentrations usually less than 150 meq/L. Hypernatremia has been detected in patients with aldosterone-producing adrenal adenomas and adrenal hyperplasia. The patients seem to ingest normal amounts of water. Adjustment of the osmosta (in the hypothalamus) to a higher than normal level of plasma osmolality seems to be the cause. Resetting of the osmostat to a higher level has rarely been noted in conditions other than primary aldosteronism. The hypernatremia can be corrected by either medical or surgical treatment of the primary aldosteronism. Mild hypernatremia in primary aldosteronism is attributable to shifting of the osmostat to the right.

Expression of steroidogenic enzyme messenger ribonucleic acids and corticosteroid production in aldosterone-producing and "nonfunctioning" adrenal adenomas.

"Nonfunctioning" adrenal adenomas are often diagnosed in patients without recognizable clinical symptoms of adrenocortical hyperfunction. The objective of this study was to determine directly the steroidogenic activity of such adenomas (n = 12) and compare them histologically and functionally to normal human adrenals (n = 6) and aldosterone-producing adenomas (n = 15). The histological appearances of nonfunctioning and aldosterone-producing adenomas were surprisingly similar. Nonfunctioning adrenal adenomas expressed all mRNAs of P450scc, P450c17, P450c21, adrenodoxin, and adrenodoxin reductase with relative levels comparable to those found in normal adrenals. Consistent with their hormone-producing nature, these adenomas had cortisol and aldosterone contents as high as those in normal adrenal tissues, a significantly (P < 0.05) increased 17-hydroxyprogesterone content, and a disproportionally low expression of P450c21 mRNA compared to aldosterone-producing adenomas. Cells isolated from both aldosterone-producing and nonfunctioning adrenal adenomas exhibited highly ACTH-sensitive cortisol and aldosterone production, suggesting again the presence of both zona glomerulosa-like and zona fasciculata-like steroidogenesis in these adenoma tissues. These results indicate that so-called nonfunctioning adrenal adenomas are not without steroidogenic activity. Therefore, the assumption that adrenal adenomas are entirely nonfunctioning in the absence of recognizable hormonal hyperfunction may not be correct.