Benign Adrenocortical Adenomas Research Articles

Robotic Posterior Retroperitoneal Adrenalectomy

To describe a robotic technique for posterior retroperitoneal (PR) adrenalectomy. Prospective study. Academic hospital. Twenty-three patients had robotic adrenalectomy within a year. Of these, 8 cases were done using a PR approach. Feasibility of the robotic approach, patient and tumor characteristics, operative time, and complications. There were 5 women and 3 men (mean age, 52 years). There were no conversions to laparoscopic or open surgery. Pathology included benign adrenocortical adenoma in 3 patients, aldosteronoma in 2, and pheochromocytoma, subclinical Cushing syndrome, and lymphangioma in 1 patient each. The right and left sides were each involved in 4 patients. The mean (SD) tumor size was 2.9 (1.7) cm. The procedures were done using 3 trocars and 5-mm robotic instruments. The mean (SD) operative time was 214.8 (40.8) minutes; docking time, 21.7 (16.6) minutes; and console time, 97.1 (24.2) minutes. Estimated blood loss was 24 (35) mL. All patients were discharged to home in 24 hours. There were no complications. Subjectively, the dissection was felt to be easier with the robotic technique compared with the laparoscopic approach owing to the improved dexterity of the instruments. To our knowledge, this is the first article describing robotic PR adrenalectomy, and we have demonstrated the technique to be feasible and safe. Owing to the limitations of a conventional laparoscopic PR approach, we believe that use of the robot is a refinement of the technique.

18F‐FDG PET for the Identification of Adrenocortical Carcinomas among Indeterminate Adrenal Tumors at Computed Tomography Scanning

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been proposed for the evaluation of adrenal tumors. However, only scarce data are available to evaluate its usefulness for the identification of primary adrenal carcinomas in patients with no previous history of cancer and equivocal tumors on computed tomography (CT) scan. The objective of the present study was to evaluate the diagnostic performance of 18F-FDG-PET to predict malignancy in such patients. This was a retrospective study carried out from 2006 to 2009 in a single university hospital center. Twenty-three consecutive patients without previous history of cancer investigated for adrenal tumors without features of benign adrenocortical adenoma on CT scan but no obvious ACC underwent 18F-FDG PET. All patients underwent adrenalectomy because of CT scan characteristics regardless of the results of 18F-FDG PET. The ratio of maxSUV adrenal tumor on maxSUV liver (adrenal/liver maxSUV ratio) during 18F-FDG PET was compared to Weiss pathological criteria. Seventeen patients had an adrenal adenoma, 2 had small size adrenal carcinomas (<5 cm), 1 had an angiosarcoma, and 3 had noncortical benign lesions. An adrenal/liver maxSUV ratio above 1.6 provided 100% sensitivity, 90% specificity, and 100% negative predictive value for the diagnosis of malignant tumor. Because of its excellent negative predictive value, 18F-FDG-PET may be of help in avoiding unnecessary surgery in patients with non-secreting equivocal tumors at CT scanning and low 18F-FGD uptake.

Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors

Histamine is involved in the pathogenesis of several tumors; however, there are no data on its possible involvement in human adrenocortical tumorigenesis. The expression of genes and proteins involved in the biosynthesis (histidine decarboxylase, HDC), action (histamine receptors: HRH1-HRH4), and metabolism of histamine is largely unknown both in the normal human adrenal cortex and in adrenocortical tumors. In this study, we examined the expression of histamine-related genes and proteins and histamine content in normal adrenal cortex, benign adrenocortical adenomas, and malignant adrenocortical cancer (ACC). Fifteen normal adrenals and 43 tumors were studied. mRNA expression was examined by real time RT-PCR. Western-blotting and immunohistochemistry were used for the study of proteins. Tissue histamine content was determined by enzyme-linked immunosorbent assay. We found that all proteins involved in histamine biosynthesis and action are present both in the normal adrenal cortex and in the tumors studied. HDC expression and histamine content was highest in the normal tissues and lower in benign tumors, whereas it was significantly less in ACCs. HRH3 expression was significantly higher in ACC samples than in the other groups. Adrenocortical tumorigenesis might, thus, be characterized by reduced histamine biosynthesis; furthermore, different adrenocortical tumor subtypes may show unique histamine receptor expression profiles.

Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT–PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time–PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study

Prognostic factors for progression of benign adrenocortical adenomas (AI) remain poorly known. We assessed the usefulness of (131)I-6-beta-iodomethylnorcholesterol scintigraphy (IMS) to predict the occurrence of adrenal hyperfunction or mass enlargement. Fifty-one consecutive inpatients with unilateral AI and normal 24-h urinary free cortisol (UFC) were enrolled in a multicenter observational prospective study to investigate the relationship between the scintigraphic pattern and the progression of biological abnormalities of the hypothalamo-pituitary-adrenal axis or tumor size. Biochemically defined 'subclinical' Cushing's syndrome (SCS) was found at baseline in 47% of patients. Unilateral uptake (UU) was significantly associated with SCS (P<0.05). During the follow-up (4.3+/-1.6-year): 53% of patients showed unchanged hormonal evaluation, 29% displayed intermittent SCS and 18% showed definitive hormonal progression of SCS but without overt biochemical hypercortisolism. UU was associated with persistence of SCS and hormonal progression (P<0.01). In multivariate analysis, UU and impaired 1 mg dexamethasone suppression were independently associated with hormonal progression. Three patients with UU developed clinical CS despite persistently normal UFC. Tumor size increased in 10% patients and was not associated with any scintigraphic pattern. Evolution of SCS toward overt biochemical CS in patients with AI is a rare event during a 4-year follow-up. UU is predictive for the occurrence of SCS, its persistence and progression within the spectrum of SCS. Further studies aiming to establish the clinical consequences of SCS are needed to recommend IMS as a complementary evaluation in patients with AI and biochemical SCS.

Immunohistochemical detection of angiotensin receptors AT1 and AT2 in adrenal tumors.

Angiotensin II is well known to affect the adrenal cell growth and function. Angiotensin receptors AT1 and AT2 were found to be present in the normal adrenal gland. However, the data on the expression of the angiotensin receptors in the adrenal tumors are very scarce. To overcome this gap, the paraffin sections of the adrenal cortical tumors and of pheochromocytomas from the archival material were immunostained with antibodies raised against AT1 (sc-1173) and AT2 (sc-9040) receptor proteins. In hyperplasia of the adrenal cortex and in benign adrenocortical adenomas, both functioning and non-functioning, the AT1 immunostaining was present mainly in the cell membranes. A positive immunoreaction was also found in the subpopulation of cell nuclei and within the cytoplasm. In the adrenal cancer, as well as in pheochromocytomas, neither cell membranes nor cell nuclei were immunostained with anti-AT1 antibody. However, a weak AT1 immunostaining was present within the cytoplasm of tumoral cells. With anti-AT2 antibody, in all tumors investigated, the tumoral cells were immunonegative but moderate to strong AT2 immunostaining was observed in the walls of intratumoral blood vessels and in the interstitial tissue. Our data indicates that the expression of AT1 receptors is altered in adrenal cancer and in pheochromocytomas. The expression of AT2 receptors, in turn, may be connected with the process of tumoral neo-angiogenesis.

505 POSTER Serum adipokine levels in colorectal cancer patients

Adrenocortical tumors (ACTs) are common, and most are benign adrenocortical adenomas (ACAs). Malignant adrenocortical carcinoma (ACC) is a rare tumor type and is observed at the rate of one or two cases per million annually. ACTs are classified as either ACAs or ACCs by histopathologic methods that are based on nine Weiss scoring criteria, including the nuclear grade, mitotic rate, presence of necrosis, and others. In this review, we describe the findings of studies that have examined the molecular basis of ACTs, and we compare transcriptome analysis with other diagnostic approaches. ACTs are occasionally difficult to classify. Therefore, molecular techniques, such as microarray analysis, have recently been applied to overcome some of these diagnostic problems. We also discuss the likelihood of the diagnosis and discernment between ACAs and ACCs based on the molecular tests. To show the recent progress in understanding the etiology of ACTs, we highlight the relationship between genetic analysis and transcriptome analysis. We attempt to understand the role of abnormal cell growth and steroid hormone secretion. Genetic and transcriptome analyses have improved our understanding of ACTs considerably, yet many unanswered questions remain.

Cushing’s Syndrome patient who exhibited congestive heart failure

Cushing's Syndrome (CS) may sometimes lead to dilated cardiomyopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilated left ventricle and an impaired left ventricular systolic function. The patient's urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient's blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Analysis by cDNA microarrays of gene expression patterns of human adrenocortical tumors

Adrenocortical carcinoma (ACC) is a rare malignant neoplasm with extremely poor prognosis. The molecular mechanisms of adrenocortical tumorigenesis are still not well understood. The comparative analysis by cDNA microarrays of gene-expression patterns of benign and malignant adrenocortical tumors allows us to identify new tumor-suppressor genes and proto-oncogenes underlying adrenocortical tumorigenesis. Total RNA from fresh-frozen tissue of 10 ACC and 10 benign adrenocortical adenomas was isolated after histologic confirmation of neoplastic cellularity of at least 85%. The reference consisted of pooled RNA of 10 normal adrenal cortex samples. Amplified RNA of tumor and reference was used to synthesize Cy3- and Cy5-fluorescently labeled cDNA in a flip-color technique. D-chips containing 11 540 DNA spots were hybridized and scanned and the images were analyzed by ImaGene 3.0 software. The comparative analysis of gene expression revealed many genes with more than fourfold expression difference between ACC and normal tissue (42 genes), cortical adenoma and normal tissue (11 genes), and ACC and cortical adenoma (21 genes) respectively. As confirmed by real-time PCR, the IGF2 gene was significantly upregulated in ACCs versus cortical adenomas and normal cortical tissue. Genes that were downregulated in adrenocortical tumors included chromogranin B and early growth response factor 1. Comprehensive expression profiling of adrenocortical tumors by the cDNA microarray technique is a very powerful tool to elucidate the molecular steps associated with the tumorigenesis of these ill-defined neoplasms. To evaluate the role of identified genes, further detailed analyses, including correlation with clinical data, are required.

Cushing’s syndrome during pregnancy secondary to adrenal adenoma: Metyrapone treatment and laparoscopic adrenalectomy

Cushing's syndrome during pregnancy is a rare and difficult to diagnose disorder. We describe the case of a 30-yr-old woman presenting with symptoms and signs of mild hypercortisolism, in which ACTH-independent Cushing's syndrome was diagnosed. Urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH levels were low. In addition, plasma cortisol failed to suppress after a high dexamethasone dose. An abdominal computed tomography scan confirmed a left adrenal mass. While diagnosis work-up was still in progress, the patient became pregnant and wanted to carry her pregnancy to full-term. Hypercortisolism was successfully controlled with metyrapone, which was started at 8 weeks of gestation. At 16 weeks of gestation, a laparoscopic left adrenalectomy was performed. Pathologic examination of the gland showed a benign adrenocortical adenoma. The patient developed secondary adrenal insufficiency and was discharged on 20 mg hydrocortisone daily dose. At 30 weeks of gestation, the patient had a pre-term rupture of membranes and underwent spontaneous vaginal delivery. The newborn was a normal virilized male who weighed 1280 g. No apparent metyrapone-induced teratogenic effects were observed and there was no clinical or biochemical suppression of adrenocortical function. In conclusion, in adrenal Cushing's syndrome during pregnancy, medical treatment with metyrapone as soon as the diagnosis is made, in combination with laparoscopic surgery during the second trimester, are useful in preventing complications secondary to hypercortisolism and safe both for the mother and infant.

Adrenal incidentaloma in pregnancy: Clinical, molecular and immunohistochemical findings

Adrenal incidentalomas detected during pregnancy are very rare, and the natural history of these tumors during gestation is unknown. We report a case of a pregnant woman with an adrenal mass discovered serendipitously, who was followed-up during gestation and underwent adrenalectomy shortly after delivery. This allowed the evaluation of both the clinical outcome and the molecular/immunohistochemical correlates. Estrogens may indeed influence the function and proliferation of human adrenal cells, and a state of circulating estrogen excess can represent an in vivo model to test their effect on the adrenals. No evidence of adrenal change in morphology and function was found in our patient throughout pregnancy, as shown by adrenal ultrasound imaging and adrenal hormone measurements. Four months after delivery, the patient underwent laparoscopic right adrenalectomy, and pathologic analysis revealed a 2.7 cm benign adrenocortical adenoma. The diameter of the adrenal mass at ultrasonography correlated highly with post-partum mass diameter measured by abdominal computed tomography (CT). Quantitative expression of both ERalpha and ERbeta by real-time RT-PCR analysis and Western blotting findings did not differ among adenoma, normal adjacent adrenal and normal adrenal control tissues. This case of an adrenal incidentaloma discovered during pregnancy shows that a close observation with endocrine investigations and ultrasonography could be an appropriate approach, delaying the decision of surgical intervention after delivery. Estrogen receptor mRNA levels in the adrenal mass similar to those observed in normal adrenals suggest that estrogen oversecretion during pregnancy was not a risk factor for tumor progression.

Plasma and tissue chromogranin in patients with adrenocortical adenomas

Adrenal adenomas frequently arise from cortical islets in the medulla, and these islets seem to present a greater risk for pathological growth than cortical cells within the adrenal cortex. Chromogranin A (CgA), a glycoprotein co-stored in secreting granules and co-released with resident hormones of chromaffin cells, behaves as a prohormone, generating several biologically active peptides capable of influencing growth, morphogenesis and progression of endocrine tumors. The aim of our study was to investigate whether chromaffin cells may be involved in the development and growth of adrenocortical adenomas. We enrolled 19 patients (12 females and 7 males, mean+/-SD age 54.9+/-11.2 yr, age range 34-75 yr) with incidental, non-functioning, benign adrenocortical adenomas, and measured circulating levels of CgA, catecholamines and creatinine before and 2 months after surgery. Plasma CgA was evaluated by immunoradiometric assay. Testing for CgA immunoreactivity in the removed tissues was performed by immunohistochemical analysis. Mean plasma CgA did not significantly change following surgery (before 73.7+/-15.2 ng/ml; after 68.9+/-14.8 ng/ml). Individual CgA values indicated that 4 patients had plasma CgA levels above our cut-off of normality. After mass removal, CgA further increased in 2 cases, decreased in 1 and normalized in 1. No variation in CgA levels was found in the other patients. No correlation was observed between CgA and the variables measured, except between CgA and plasma creatinine (r=0.472, p<0.05). Histopathological evaluation revealed adrenocortical adenomas in all cases and immunohistochemical analysis detected no CgA immunoreactivity in any specimen. Our results show that in human adrenocortical adenomas CgA is not expressed and that removal of the mass does not modify plasma CgA levels. For these reasons the endocrine involvement of local CgA in adrenocortical tumorigenesis is unlikely.

Plasma chromogranin A in incidental non-functioning, benign, solid adrenocortical tumors.

To evaluate whether adenomas arising from the adrenal cortex, a tissue of epithelial origin, are associated with high chromogranin A (CgA) levels and whether such tumors may express and release this protein. In addition, to investigate whether high CgA levels imply a neuroendocrine differentiation of the adrenocortical adenomas and, therefore, represent a humoral marker of malignant transformation of these tumors. Plasma CgA of 80 patients with non-functioning, benign adrenocortical adenomas was compared with that of 137 tumor-free subjects. In 15 patients, the masses were surgically removed and CgA was measured 2 months later. The other 65 patients with adrenocortical adenomas underwent clinical and radiological follow-up (range 24-36 months). CgA was evaluated by immunoradiometric assay in peripheral blood and by immunohistochemistry in adrenal tissue specimens. An increase in plasma CgA (P<0.001) was observed in patients with adrenocortical adenomas (83.4+/-7.5 ng/ml) in comparison with tumor-free subjects (43.1+/-1.5 ng/ml). The prevalence of high CgA levels was 25% in the former and 0.7% in the latter. By multiple regression analysis, an increase (49%) in the expected median CgA value was estimated for adrenocortical adenomas (P<0.001). Receiver operating characteristic analysis showed a good diagnostic performance of CgA in identifying patients with adrenocortical adenomas (pure accuracy=0.78, 95% CI=0.71-0.84). In the operated patients, CgA levels did not change before (80.6+/-16.5 ng/ml) and after (74.3+/-16.3 ng/ml) surgery and in no case was CgA immunoreactivity found in adenoma tissues. The non-operated patients did not develop signs or symptoms of disease and showed no features of malignant transformation of the masses. Our data showed a strong association between adrenocortical adenomas and high CgA levels. CgA hypersecretion was not due to adenoma tissue, which did not show immunoreactivity for CgA. Finally, elevated CgA levels did not represent a humoral marker of malignant transformation of cortical adenomas.

Clinical and molecular aspects of adrenocortical tumourigenesis.

Adrenal masses are a common problem affecting 3-7% of the population. The majority turn out to be benign adrenocortical adenomas, which may be functional or non-functional. Much more rarely, these masses represent a primary adrenal carcinoma. It is becoming increasingly recognized that of the benign functioning adenomas or hyperplasias, the majority will hypersecrete aldosterone and this will be more frequently detected when hypertensive populations are screened for this disease. In contrast, the incidence of primary adrenocortical carcinoma has remained steady and for this disease, surgery represents the mainstay of treatment. The advent of laparoscopic adrenal surgery has lowered the threshold size for recommending surgery for asymptomatic adrenal masses and as such, an increased proportion of adrenocortical cancers are being resected and detected at an earlier stage. Recent progress has been made in our understanding of the key genetic changes which underpin the biology of this disease. Progression from adrenal adenoma to carcinoma involves a monoclonal proliferation of cells which, among other defects, have undergone chromosomal duplication at the 11p15.5 locus leading to overexpression of the IGF2 gene and abrogation of expression of the CDKN1C and H19 genes. TP53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored. Other key oncogenes and tumour suppressor genes remain to be identified although the chromosomal loci in which they lie can be identified at 17p, 1p, 2p16 and 11q13 for tumour suppressor genes and chromosomes 4, 5 and 12 for oncogenes.

Adrenal incidentalomas.

The term adrenal incidentaloma refers to an adrenal mass occasionally and unexpectedly discovered by an abdominal imaging procedure performed for reasons a priori unrelated to adrenal dysfunction. The prevalence of adrenal incidentalomas as discovered by computed tomographic scan examination is estimated to be between 1% and 4%. The vast majority of these lesions are of adrenocortical origin, most often adenomas. Identification of steroid or catecholamine-secreting tumors is important but usually solved with appropriate endocrinologic investigations. A difficult problem, however, is to distinguish between benign and malignant primary or secondary tumors. Size less than 4 cm and an unenhanced computed tomographic attenuation under 10 Hounsfield Units (HU) are findings in favor of a benign adrenocortical adenoma, as is a positive NP 59 scintigraphic examination. The pathogenesis of adrenal tumors is not well understood. However, alterations of the cyclic AMP signalling pathway have recently been observed in benign adrenocortical lesions and molecular defects associated with insulin-like growth factor-II overexpression in malignant adrenocortical tumors.

Overexpression of Glutathione-S-Transferase A1 in Benign Adrenocortical Adenomas from Patients with Cushing's Syndrome

Overexpression of Glutathione-S-Transferase A1 in Benign Adrenocortical Adenomas from Patients with Cushing's Syndrome

Overexpression of Glutathione-S-Transferase A1 in Benign Adrenocortical Adenomas from Patients with Cushing’s Syndrome

Benign adrenocortical adenoma is a major primary cause of Cushing's syndrome. Although numerous studies have been performed, the molecular mechanism of adrenocortical adenoma is yet to be elucidated. In this study we endeavored to identify genes differentially regulated in adrenocortical adenoma by suppression PCR-based complementary DNA (cDNA) subtractive hybridization. The cDNA population in atrophied nontumorous adrenal gland adjacent to the adenoma was subtracted from that in the adenoma. Then adenoma-specific cDNAs were amplified by PCR. We cloned several cDNAs that are selectively up-regulated in the adenoma, one of which was identified to encode glutathione-S-transferase A1 (GSTA1). Northern blot analysis revealed that GSTA1 messenger ribonucleic acid was abundantly expressed in the adenoma compared with that in the adjacent atrophied nontumorous gland. Western blot analysis and immunohistochemistry showed high expression of GSTA1 also at the protein level. In concordance with this finding, GST activity was significantly higher in the adenoma than in the adjacent atrophied nontumorous gland. To clarify the role of GSTA1 in adrenocortical cells, GST activity in the H295R human adrenocortical cell line was inhibited by ethacrynic acid. Inhibition of GSTs interfered with proliferation of the cells. We, therefore, hypothesize that overexpression of GSTA1 in adrenocortical adenomas might be involved in the growth of tumor cells. We also speculate that this overexpression might be an adaptive response to excess cortisol production.

Alpha1 connexin 43 gap junctions are decreased in human adrenocortical tumors.

Gap junctional communication disorders have been implicated in the etiology of benign and malignant tumors. Understanding the type, distribution, and frequency of gap junctions in adrenal disorders should provide insight into the role of gap junctions in adrenal carcinogenesis as well as information that may be useful in developing improved diagnosis and treatment of adrenal diseases. Using immunocytochemical techniques, we have characterized and compared alpha1 connexins 43 gap junction protein levels in normal adrenal glands to those in benign and malignant adrenocortical human tumors. In addition, gap junction protein levels were studied in a human adrenal cancer cell line (H295). In both normal and neoplastic adrenal tissues, only alpha1 connexin 43 could be detected, whereas beta1 connexin 32 and beta2 connexin 26 were not found. In the normal adrenal gland, the zona fasciculata was demonstrated to have the highest number of gap junctions per cell (mean +/- SEM, 13.78 +/- 1.93). In contrast, in benign adrenocortical adenomas, the number of gap junctions per cell compared to that detected in normal adrenal glands was significantly reduced (mean +/- SEM, 4.6 +/- 1.17; P < or = 0.05), and the lowest number was found in malignant adrenocortical tumors (1.42 +/- 0.58; P < or = 0.05). Similarly, there were few or no alpha1 connexin 43 gap junctions in the H295 population. There was a progressive decrease in gap junction plaques in adrenocortical cancer cell populations compared to those in normal cell populations. Therefore, analysis of gap junction protein may be helpful for the differential diagnosis of benign and malignant adrenal tumors. The induction of gap junctions in malignant cells may provide a novel therapeutic strategy for adrenal cancer.

Telomerase Activity Is Significantly Enhanced in Malignant Adrenocortical Tumors in Comparison to Benign Adrenocortical Adenomas

Telomerase Activity Is Significantly Enhanced in Malignant Adrenocortical Tumors in Comparison to Benign Adrenocortical Adenomas

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study. Prospective study evaluating the prevalence of unilateral IMC uptake (tumour uptake with no visualization of the contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and the contralateral adrenal glands) in patients with unilateral incidentaloma. Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM) in the two scintigraphic groups thus defined. Thirty-five patients with a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan. The IMC scan was performed in basal conditions (baseline scan) and after DXM (suppression scan). Adrenocortical function assessment included basal measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test. The baseline scan showed 16 patients (46%) with unilateral uptake (group A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an overnight DXM suppression test (P = 0.02), than did patients in group B. In addition, 3 patients in group A failed the overnight and the low-dose DXM suppression tests. Adrenal masses were larger in group A than group B (P = 0.04) and an inverse correlation was found in the whole population between tumour size and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14 patients (7 in each group), patients in group A continued to exhibit unilateral tumour uptake and bilateral uptake was suppressed in 72% of patients in group B. An adrenal mass was removed in 3 patients of group A with confirmed benign adrenocortical adenomas. In the post-surgical period, the contralateral gland was again visualized in a baseline scan and the hormonal evaluation returned to the normal range. Unilateral 131I-6 beta-iodomethylnorcholesterol tumour uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and scintigraphic profiles obtained after dexamethasone, as well as hormonoscintigraphic changes observed after surgery, provide evidence that unilateral uptake is related to functioning adenomas with various degrees of autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could be a valuable tool for screening 'subclinical' Cushing's adenomas.