Benign Adrenocortical Adenomas Research Articles

Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2-3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10-40% of the cases by autonomous cortisol hypersecretion, and in 1-10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients.

The role of steroid metabolome analysis for the diagnosis and follow-up of adrenocortical tumors.

The diagnostic work-up of adrenal tumors, often incidentally discovered, has emerged as an ever-increasing diagnostic problem for clinical endocrinologists. No imaging modality has sufficiently high sensitivity and specificity at differentiating benign from malignant adrenal lesions. It has long been observed that adrenocortical carcinomas (ACCs) present an immature pattern of steroidogenesis, dominated by steroid hormone precursors. Modern mass spectrometry-based assays can generate multi-steroid metabolite profiles in urine collections, which can detect differences between ACCs and benign adrenocortical adenomas (ACAs). This review summarizes the promising results of studies which have applied steroid metabolite profiling in biological fluids as a novel diagnostic tool for patients with adrenal tumors, as well as the challenges and limitations of this approach. It also discusses the potential role of steroid profiling as a biochemical surveillance tool to detect recurrence in patients who have undergone resection of an ACC.

Suppression of Forkhead Box Protein O1 (FOXO1) Transcription Factor May Promote Adrenocortical Tumorigenesis.

Despite recent comprehensive genetic analyses, molecular evidence for a pathophysiological continuum linking benign adrenocortical adenoma (ACA) and highly aggressive adrenocortical carcinoma (ACC) is still elusive. Using human tumor samples and the established ACC cell line SW-13, this study investigated potential regulatory roles for FOXO transcription factors, in modulating adrenocortical tumorigenesis. Adrenocortical tumor specimens (20 ACAs, 10 ACCs, and 9 normal adrenal tissue samples) obtained from 30 patients were analyzed for ubiquitously expressed FOXO transcription factors, FOXO1 and FOXO3 using qRT-PCR and immunohistochemistry. The SW-13 ACC cells were used to study the phenotypic effects of FOXO regulation in vitro. While FOXO3 expression remained unchanged in ACCs, FOXO1 expression was found to be significantly downregulated in 19/20 ACAs and 9/10 ACCs (p<0.0001 and p<0.05, respectively), suggesting a global role for FOXO1 suppression in promoting and maintaining adrenocortical dedifferentiation. Silencing of FOXO1 in SW-13 cells resulted in significant loss of viability (p<0.001) mediated by apoptosis as determined by quantitative Annexin V immunofluorescence analysis (p<0.01). FOXO1 silencing also augmented the migratory behavior of SW-13 cells (p<0.0001), suggesting distinct roles for FOXO1 in promoting viability and controlled motility of adrenocortical cells.

Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling.

Adrenal masses are highly prevalent, found in 5% of the population. Differentiation of benign adrenocortical adenoma from adrenocortical carcinoma is currently hampered by the poor specificity and limited evidence base of imaging tests. This review summarizes the results of studies published to date on urine steroid metabolite profiling for distinguishing benign from malignant adrenal masses. Three studies have described cohorts of at least 100 patients with adrenal tumors showing significant differences between urinary steroid metabolite excretions according to the nature of the underlying lesion, suggesting significant value of steroid metabolite profiling as a highly accurate diagnostic test. Steroid profiling is emerging as a powerful novel diagnostic tool with a significant potential for improving the management for patients with adrenal tumors. Although the current studies use gas chromatography-mass spectrometry for proof of concept, widespread use of the method in routine clinical care will depend on transferring the approach to high-throughput tandem mass spectrometry platforms. The use of computational data analysis in conjunction with urine steroid metabolite profiling, that is, steroid metabolomics, adds accuracy and precision.

Robot-assisted adrenalectomy: indications and drawbacks.

Adrenal tumors can vary from a benign adrenocortical adenoma with no hormonal secretion to a secretory adrenocortical malignancy (adrenocortical carcinoma) or a hormone-secreting tumor of the adrenal medulla (pheochromocytoma). Currently, laparoscopic adrenalectomy is regarded as the preferred surgical approach for the management of most adrenal surgical disorders, although there are no prospective randomized trials comparing this technique with open adrenalectomy. However, widespread adoption of robotic technology has positioned robotic adrenalectomy as an option in some medical centers. Speculative advantages associated with the use of the robotic system have rarely been evaluated in clinical settings and cost increase remains an important drawback associated with robotic surgery. This review summarizes current available data regarding robotic transperitoneal adrenalectomy including its indications, advantages, limitations, and comparison with conventional laparoscopic adrenalectomy. We believe that the use of a robotic system seems to be useful especially in more difficult patients with larger tumors, truncal paragangliomas, and bilateral and/or partial adrenalectomies. Overall, we believe that overcosts due to robotic system use could be balanced by hospital stay decrease, patients' referral increase, improved postoperative outcomes in more difficult patients and ergonomics for the surgeon. However, we also believe that the current surgical intuitive business model is counterproductive, because there are no available strong clinical data that could balance overcosts associated with the use of the robotic system.

Recommendations for the management of adrenal incidentalomas: what is pertinent for radiologists?

Adrenal incidentalomas are unsuspected, asymptomatic adrenal masses detected on imaging. Most are non-functioning benign adrenocortical adenomas but can represent other benign lesions or lesions requiring therapeutic intervention including adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis. This review summarizes and highlights radiological recommendations within the recently issued guidelines for the management of adrenal incidentalomas from the European Society of Endocrinology Clinical Practice in collaboration with the European Network for Study of Adrenal Tumours. Four pre-defined clinical questions were addressed in the guidelines and two have specific relevance and implications for radiologists: (1) how to assess risk of malignancy on imaging and (2) what follow-up is indicated if an adrenal incidentaloma is not surgically removed? The guidelines also include recommendations for frequently encountered special circumstances, including bilateral incidentalomas, incidentalomas in patients with extra-adrenal malignancy and in the young and elderly patients. This review highlights radiological recommendations within the guidelines and evidence used for formulating the guidelines.

Hypokalemic myopathy in primary aldosteronism: A case report.

Primary aldosteronism (PA) is a rare disorder. The majority of patients with PA present with typical features and are easily diagnosed. This disorder is usually diagnosed with hypokalemia, hypertension or an adrenal mass. However, patients with atypical symptoms may present a challenge for diagnosis and treatment. In the present study, a case of PA is described that presented with hypokalemic myopathy simulating polymyositis. The patient was a 44-year-old woman who presented with weakness and difficulty walking. The patient was initially suspected to have PM and was treated with methylprednisolone. The patient was found to have hypokalemia which persisted despite high-dose supplementation of potassium. Adrenal computed tomography revealed a right adrenal mass. Surgical adrenalectomy was conducted. The final pathological diagnosis was benign adrenocortical adenoma. The serum tests remained normal and the patient's symptoms were resolved during the 8-month follow-up.

Novel Insights into the Genetics and Pathophysiology of Adrenocortical Tumors.

Adrenocortical tumors (ACTs) are typically unilateral and can be classified as benign adrenocortical adenomas (ACAs) or malignant adrenocortical cancers (ACCs). In rare cases, tumors may occur in both adrenal glands as micronodular hyperplasia (primary pigmented nodular adrenal dysplasia) or as macronodular hyperplasia (primary bilateral macronodular adrenal hyperplasia, PBMAH). The study of certain tumor predisposition syndromes has improved our understanding of sporadic ACTs. Most ACAs are associated with abnormalities of the cAMP signaling pathway, whereas most ACCs are linked to alterations in IGF2, TP53, or the Wnt/βcatenin pathways. Over the past year, single-nucleotide polymorphism array technology and next-generation sequencing have identified novel genetic alterations in ACTs that shed new light on the molecular mechanisms of oncogenesis. Among these are somatic mutations of PKA catalytic subunit alpha gene (PRKACA) in ACA, germline, and somatic mutations of armadillo repeat containing 5 gene (ARMC5) in primary bilateral macronodular adrenal hyperplasia and somatic alterations of the E3 ubiquitin ligase gene ZNRF3 in ACC. This review focuses on the recent discoveries and their diagnostic, prognostic, and therapeutic implications.

PP.26.25

Objective: Resistant arterial hypertension is defined as above of blood pressure (BP) > 140/90 mmHg despite therapy with three or more antihypertensive medications of different classes at maximum tolerable doses with one being diuretic. Design and method: An important consideration in defining a patient with resistant hypertension is the mislabeling of secondary hypertension as resistant hypertension. Secondary forms of arterial hypertension are not rare and are frequently associated with treatment resistance unless the etiological factor is removed. Here we report a 58 -year-old woman with resistant hypertension, BP of 220/110 mmHg on four anthypertensive drugs, post-prandial pain and left adrenal mass incidentally discovered. Results: The results of hormonal test revealed a subclinical Cushing's syndrome, and a renal ultrasonography, including Doppler, revealed that the longitudinal size of both kidney was different from each other (right 11 cm, left 7 cm) and the renal blood flow was decreased in the left kidney. An abdominal CT with arterial phase confirmed the left adrenal mass (30 x 20 mm of diameter) and revealed a thrombosis of the superior mesenteric artery, stenosis of left renal artery, and stenosis of common iliac artery. Extensive laboratory evaluation revealed positivity of lupus anticoagulant (LAC), and antiphospholipidic syndrome (APS) was posed. At different times before the patient underwent revascularization of the mesenteric and left renal arteries and then laparoscopic left adrenalectomy. Hystopathological examination consistent with a benign adrenocortical adenoma. At subsequent outpatient review, optimal BP was achieved (140/85 mmHg) with anthypertensive treatment, the glucocorticoid hormones were within normal range and a duplex ultrasound evidenced elevated velocities within the left renal artery. Conclusions: In conclusion, we report a patient with resistant hypertension caused by multiple steno-occlusive arteries due to APS and coesisting with subclinical Cushing syndrome.

Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas.

Incidental benign adrenocortical adenomas, adrenal incidentalomas are found in 4.5% of abdominal computed tomography scans, with the incidence increasing to 10% in patients older than 70 years of age. These incidentalomas frequently show evidence of excess cortisol secretion but without overt Cushing's syndrome. The mortality rate is increased in Cushing's syndrome. This study sought to investigate whether patients with adrenal incidentalomas have an increased mortality. This was a retrospective, longitudinal cohort study. The study was carried out in an Endocrine Investigation Unit in a University Teaching Hospital. Two hundred seventy-two consecutive patients with an incidental adrenal mass underwent a dedicated diagnostic protocol, which included dexamethasone testing for hypercortisolism between 2005 and 2013. Overall survival was assessed in 206 patients with a benign, adrenocortical adenoma. Survival analysis was carried out by using Kaplan-Meier curves and the effect of dexamethasone cortisol estimated by Cox-regression analysis. Cause-specific mortality was ascertained from death certificates and compared with local and national data. Eighteen of 206 patients died and the mean time (SD) from diagnosis to death was 3.2 (1.7) years. Seventeen of 18 patients who died had a post dexamethasone cortisol >1.8 μg/dL and there was a significant decrease in survival rate with increasing dexamethasone cortisol levels (P = .001). Compared with the <1.8 μg/dL group, the hazard ratio (95% confidence interval) for the 1.8-5 μg/dL group was 12.0 (1.6-92.6) whereas that of the >5 μg/dL group was 22.0 (2.6-188.3). Fifty percent and 33% of deaths were secondary to circulatory or respiratory/infective causes, respectively. PATIENTS with adrenal incidentalomas and a post-dexamethasone serum cortisol >1.8 μg/dL have increased mortality, mainly related to cardiovascular disease and infection.

Epigenetic silencing of RASSF1A deregulates cytoskeleton and promotes malignant behavior of adrenocortical carcinoma

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational heterogeneity and a generally poor clinical outcome. Despite implicated roles of deregulated TP53, IGF-2 and Wnt signaling pathways, a clear genetic association or unique mutational link to the disease is still missing. Recent studies suggest a crucial role for epigenetic modifications in the genesis and/or progression of ACC. This study specifically evaluates the potential role of epigenetic silencing of RASSF1A, the most commonly silenced tumor suppressor gene, in adrenocortical malignancy.ResultsUsing adrenocortical tumor and normal tissue specimens, we show a significant reduction in expression of RASSF1A mRNA and protein in ACC. Methylation-sensitive and -dependent restriction enzyme based PCR assays revealed significant DNA hypermethylation of the RASSF1A promoter, suggesting an epigenetic mechanism for RASSF1A silencing in ACC. Conversely, the RASSF1A promoter methylation profile in benign adrenocortical adenomas (ACAs) was found to be very similar to that found in normal adrenal cortex. Enforced expression of ectopic RASSF1A in the SW-13 ACC cell line reduced the overall malignant behavior of the cells, which included impairment of invasion through the basement membrane, cell motility, and solitary cell survival and growth. On the other hand, expression of RASSF1A/A133S, a loss-of-function mutant form of RASSF1A, failed to elicit similar malignancy-suppressing responses in ACC cells. Moreover, association of RASSF1A with the cytoskeleton in RASSF1A-expressing ACC cells and normal adrenal cortex suggests a role for RASSF1A in modulating microtubule dynamics in the adrenal cortex, and thereby potentially blocking malignant progression.ConclusionsDownregulation of RASSF1A via promoter hypermethylation may play a role in the malignant progression of adrenocortical carcinoma possibly by abrogating differentiation-promoting RASSF1A- microtubule interactions.

Detection of Circulating Tumor Cells in Patients With Adrenocortical Carcinoma: A Monocentric Preliminary Study

Adrenocortical carcinoma (ACC) is a rare malignancy, the prognosis of which is mainly dependent on stage at diagnosis. The identification of disease-associated markers for early diagnosis and drug monitoring is mandatory. Circulating tumor cells (CTCs) are released into the bloodstream from primary tumor/metastasis. CTC detection in blood samples may have enormous potential for assisting in the diagnosis of malignancy, estimating prognosis, and monitoring the disease. The aim of the study was to investigate the presence of CTCs in blood samples of patients with ACC or benign adrenocortical adenoma (ACA). We conducted the study at a university hospital. CTC analysis was performed in blood samples from 14 ACC patients and 10 ACA patients. CTCs were isolated on the basis of cell size by filtration through ScreenCell devices, followed by identification according to validated morphometric criteria and immunocytochemistry. We measured the difference in CTC detection between ACC and ACA. CTCs were detected in all ACC samples, but not in ACA samples. Immunocytochemistry confirmed the adrenocortical origin. When ACC patients were stratified according to the median value of tumor diameter and metastatic condition, a statistically significant difference was found in the number of CTCs detected after surgery. A significant correlation between the number of CTCs in postsurgical samples and clinical parameters was found for tumor diameter alone. Our findings provide the first evidence for adrenocortical tumors that CTCs may represent a useful marker to support differential diagnosis between ACC and ACA. The correlation with some clinical parameters suggests a possible relevance of CTC analysis for prognosis and noninvasive monitoring of disease progression and drug response.

Virilization in a Girl with Adrenocortical Adenoma: A Case Report

We present a case of Cushing’s syndrome and virilization in a 15 year old girl which was suspected to be due to an adrenal carcinoma. She presented with features of virilization in addition to those of hypercortisilism. Her high androgen levels especially dehydroepiandrosterone sulfate (DHEAS) were also in favor of an adrenal carcinoma. An unenhanced computerized tomography (CT) scan showed a mass (size: 5.3 cm) in the right adrenal gland with a soft tissue intensity of more than 10 HU which was suggestive of adrenal carcinoma. But, histopathology of the resected mass revealed a benign adrenocortical adenoma. DOI: http://dx.doi.org/10.3329/imcj.v6i2.14736 Ibrahim Med. Coll. J. 2012; 6(2): 70-72

CpG Island Methylator Phenotype in Adrenocortical Carcinoma: Fact or Fiction?

CpG Island Methylator Phenotype in Adrenocortical Carcinoma: Fact or Fiction?

Gene expression and regulation in adrenocortical tumorigenesis.

Adrenocortical tumors are frequently found in the general population, and may be benign adrenocortical adenomas or malignant adrenocortical carcinomas. Unfortunately the clinical, biochemical and histopathological distinction between benign and malignant adrenocortical tumors may be difficult in the absence of widely invasive or metastatic disease, and hence attention has turned towards a search for molecular markers. The study of rare genetic diseases that are associated with the development of adrenocortical carcinomas has contributed to our understanding of adrenocortical tumorigenesis. In addition, comprehensive genomic hybridization, methylation profiling, and genome wide mRNA and miRNA profiling have led to improvements in our understanding, as well as demonstrated several genes and pathways that may serve as diagnostic or prognostic markers.

Cushing’s Syndrome during Pregnancy: Post Delivery Adrenalectomy Consequent to Medical Management without Adrenal Enzyme Inhibitors

A 32-year-old female, gravid two, para one, with Cushing’s syndrome (CS) was admitted to our hospital at 25 week of gestation with severe hypercortisolism. Basal urinary free cortisol (UFC) was elevated about 10 times above the upper limit of normal in two separate times and plasma cortisol failed to suppress after an overnight 1mg dexamethasone suppression test but Adrenocorticotropic hormone (ACTH) level was suppressed. An abdominal non-contrast magnetic resonance imaging (MRI) disclosed a 3-cm right adrenal mass (Fig. 1). Due to her critical general condition, the adrenalectomy was not performed. At 30 week of gestation, by the diagnosis of severe preeclampsia she underwent an emergent cesarean section. Two weeks later, right adrenalectomy was performed via laparotomy. Pathologic examination of the gland showed a benign adrenocortical adenoma. The newborn was a healthy male who weighed 1850 gram. There was no clinical or biochemical suppression of adrenocortical function in child and they were discharged after 40 days.[GMJ. 2012;1(1):38-41]

Peritoneal Carcinosis in Apparently Benign Cortisol Producing Adrenal Adenoma≥5 cm in Diameter: The Need of Regular Postoperative Surveillance

Clinical and histopathological distinction between benign and malignant adrenocortical tumors can be a challenge.Report on 2 patients with cortisol producing apparently benign adrenal adenomas ≥ 5 cm in diameter with local malignant recurrence and peritoneal carcinomatosis after endoscopic surgery. Case 1: The 59-year-old male presented with adrenal hypercortisolism due to a 5.0 cm large adrenal tumor on the left side. A retroperitoneoscopic total adrenalectomy was performed. Histologically, a benign adrenal adenoma (Weiss score 1, Ki-67 < 2%) was found. 6 months later, the patient developed clinically and biochemically recurrent disease with recurrent tumor in the left adrenal region and peritoneal carcinomatosis. The patient died 5 months after second surgery. Case 2: The 32-year-old female was pregnant in 27th week when presenting with adrenal hypercortisolism due to a 5.5 cm large adrenal tumor on the left side. She was operated on using a laparoscopic approach and a total adrenalectomy was carried out. Histological examination revealed a benign adrenocortical adenoma (Weiss score 1, Ki-67 < 5%). 4 years later, the patient came back with clinically and biochemically recurrent disease. Imaging showed a 10 cm large tumor in the left retroperitoneum and a diffuse peritoneal carcinomatosis. The patient died 2 months after diagnosis. Cortisol producing adrenal tumors ≥ 5 cm in diameter are at risk to be misdiagnosed as apparently benign. Regular surveillance should be considered in patients presenting with large cortisol producing tumors.

Subclinical hypercortisolism: debatable or visible on the lightbox?

Adrenal nodules unrelated to clinically overt adrenal disease became visible more than 120 years ago ever since the first autopsy studies [1]. Nowadays, through the development of modern radiology modalities, adrenal nodules previously identified only at autopsy or surgery, are easily visible during imaging of the abdomen. The importance of this for the practicing endocrinologist is highlighted by the fact that hardly a week goes by without a patient being referred for further evaluation of an incidentally depicted adrenal mass. Despite, however, the high prevalence of adrenal incidentalomas, about 4 % in the middle-age population, approaching 7 % in the elderly ones [2, 3], and an ongoing stream of published papers, its relevance for the patient remains in many occasions largely inconclusive. The vast majority of adrenal incidentalomas are benign adrenocortical adenomas although rare entities, such as myelolipomas, cysts, ganglioneuromas, onconcytomas, may also be encountered. A significant proportion of patients, about 15 %, have bilateral lesions [4]. Since most adrenal incidentalomas arise from adrenal tissue, a substantial proportion of them are functional in terms of autonomous production of various adrenal hormones, including cortisol, aldosterone, catecholamines or rarely androgens. Subclinical hypercortisolism (SH), defined by an abnormal endocrine work-up indicating autonomous cortisol secretion in the absence of obvious clinical stigmata of Cushing’s syndrome, is by far the most commonly encountered abnormality. It is detected in a varying proportion of subjects, between 1 and 47 %, depending on the diverse criteria used to define it [5]. The finding of an adrenal mass undoubtedly raises concerns about the possibility of malignancy but adrenocortical cancer in this context is rare, especially when the size of the lesion is less than 4.0 cm, as is the case with most adrenal incidentalomas [6]. Thankfully, differentiation between benign and malignant adrenal lesions is visible with much accuracy with current imaging techniques. On CT scanning, which is the modality of choice for evaluating the adrenal glands, adrenocortical adenomas are well-circumscribed ovoid masses with typically low attenuation values (less than 10 HU) on unenhanced images, due to the high content in lipids. The 20–30% of lipid-poor adrenal adenomas that exhibit higher attenuation values can be further evaluated either using contrast washout techniques or MRI scans. Benign adenomas on CT show an absolute and a relative percentage of contrast washout of more than 60 and 40 %, respectively. MRI may provide additional information for the few remaining indeterminate lesions, using T1-weighted, T2-weighted, and especially chemical shift imaging (CSI); benign adenomas are homogenous, have low or equal signal intensity compared to the liver on T2-weighted images and demonstrate significant signal intensity loss on out-of-phase CSI compared to the in-phase images. Thus, radiology has a major role in identifying the rare cases of malignancy among adrenal incidentalomas through the initial imaging phenotype combined with a repeat scan to evaluate potential rapid and significant increase in size. In this Endocrine issue Olsen et al. [7] in a multicentre, prospective study attempt to expand the usefulness of imaging visibility toward a functional perspective. The authors investigated 235 patients presenting with benign appearing incidentally detected adrenal masses and correlated CT findings such as unenhanced attenuation value, size, and bilaterality with the hormonal work-up for the presence of SH. Previous observational data have shown a consistent relationship between the size of the adenoma D. A. Vassiliadi S. Tsagarakis (&) Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, 45 Ipsilantou St, 106 76 Athens, Greece e-mail: stsagara@otenet.gr

Imaging of Adrenal Masses with Emphasis on Adrenocortical Tumors

Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings (“incidentalomas”). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [18F]fluoro-deoxy-glucose (18FDG), is able to differentiate benign from malignant adrenal tumors in many patients. 11C-metomidate (11C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

Transcriptome analysis of adrenocortical cancers (ACC): from molecular classification to the identification of new treatments

Transcriptome analysis has been successfully used to study the gene profile expression of adrenocortical tumors (ACT) for 7 years. The various studies reported to date have produced an abundance of new information on adrenocortical cancer (ACC), underlying the validity of this approach to study the molecular genetics and pathogenesis of these tumors. The gene expression profile of ACC clearly differs from that of benign adrenocortical adenomas (ACA). Interestingly, transcriptome analysis has the ability to establish a subclassification of ACC based on the gene expression profile. In particular, it is able to identify two groups of tumors with different outcomes (i.e. good prognosis and poor prognosis). This approach has been used to develop molecular markers for ACC diagnosis and prognostication. An IGF2 cluster of genes up-regulated in ACC has been identified. Transcriptome analysis has shown that, in comparison with ACA, IGF2 is indeed the gene most overexpressed in ACC. By contrast, genes associated with steroidogenesis are down-regulated in ACC. Genes controlling the cell cycle are dysregulated in ACC, and several are dramatically overexpressed. Analysis regarding the level of expression of Wnt/β-catenin and p53 signaling has shown alterations, in keeping with the known molecular somatic genetic defects of these pathways that are observed in ACC. This review summarizes the main findings of studies reporting ACC transcriptome analysis, demonstrating its power for ACT classification, and examines the resulting progress in understanding the pathogenesis of ACC. The potential for both ACC diagnosis and the identification of new therapeutic targets will be discussed.