Adrenal Cortical Tumors Research Articles

The Role of gsp Mutations on the Development of Adrenocortical Tumors and Adrenal Hyperplasia.

Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune–Albright syndrome (MAS) and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors, and primary macronodular adrenocortical hyperplasia (PMAH) (1–3). The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear (3). PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of MAS. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production (2, 4). With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion. In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia.

Experience with surgical treatment for primary malignant adrenal tumors

Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately. Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7)) with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80) years (median age 51.0 years). The right and left adrenal glands were affected in 49 (36.9 %) and 77 (57.9 %) patients, respectively; both adrenal glands were involved in 7 (5.3 %). A group of 21 (15.8 %) people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups. Results. The investigation analyzed treatment results in 21 (15.8 %) patients with primary malignant adrenal lesions (Group 1). The most common morphological form was adrenocortical carcinoma in 15 (11.3 %) patients (5 men and 10 women (1:2)); their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell carcinoma, Castleman’s disease, and oncocytic carcinoma. According to the tumor stage, the patients with adrenocortical carcinoma were divided as follows: Stage T1 (n = 3), Stage T2 (n = 3), Stage T3 (n = 4), and Stage T4 (n = 5). In the patients with adrenocortical carcinoma, the size of an adrenal tumor was 8.7 ± 4.9 cm; hypertension as a main clinical manifestation occurred in 5 patients; pain syndrome was observed in 10; hormonal activity was noted in 8, blood electrolyte disorders were seen in 3, and gastrointestinal manifestations were in 9 patients. In Group 1, 8 (38.1 %) patients were survivors and 13 (61.9 %) patients died. Moreover, the overall 5-year survival was 37.9 %. Five-year survival in patients with adrenocortical carcinoma was 42.4 % (6 (53.3 %) survivors and 9 (46.7 %)) dead persons); that in patients with other malignant adrenal tumors was 33.3 % (2 (33.3 %) survivors and 4 (66.7 %) dead persons). Conclusion . Surgical removal of an adrenocortical tumor is the only treatment option that can cure a patient or considerably prolong life particularly if the disease is detected at stage I or II.

Adrenal Cortical Tumor with Rare Presentation of Psychosis

Adrenal cortical tumors are rare tumors and the common presenting symptoms are related with excessive glucocorticoids secretions leading to cushinoid features and systemic manifestations of the excess steroids hormonal secretions We are presenting a case of Adrenal cortical tumor presenting as primarily psychosis nbsp hence Adrenal cortical tumor should always be considered in the differential diagnosis of evaluation of psychosis

Retroperitoneal Fat Necrosis in a Patient with Extensive Weight Loss After Adrenalectomy for ACTH-Independent Cushing Syndrome: A Case Report and Review of the Literature

ABSTRACT Objective: To report a case of retroperitoneal fat necrosis (RFN) found after extensive weight loss following left adrenalectomy in a woman with Cushing syndrome. Methods: Case-based review of RFN without pancreatic disorders. We performed a PubMed search using the search term ‘retroperitoneal fat necrosis.’ Results: A 33-year-old woman with Cushing syndrome developed bilateral fat-containing infiltrative soft-tissue neoplasms in the perinephric space, measuring 5.0 × 7.5 cm (right) and 7.8 × 8.1 cm (left), with numerous enlarged retroperitoneal lymph nodes and fat stranding, 10 months post–left adrenalectomy for a 9-cm adrenal cortical neoplasm of uncertain malignant potential. Both computed tomography (CT)-guided core-needle biopsy followed by exploratory laparotomy with biopsy of the retroperitoneal masses showed that it was fat necrosis (FN) surrounded by a narrow rim of fibrous tissue with chronic inflammation. No further intervention was initiated, and CT abdomen 27-months postsurgery demon...

USP10 Expression in Normal Adrenal Gland and Various Adrenal Tumors

Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, is associated with androgen receptor transcriptional activity and pathological processes of tumor. However, information between USP10 and the adrenal gland is limited. In particular, the role of USP10 in adrenal tumors has not been elucidated yet. This study aims to investigate the expression of USP10 in the human normal adrenal gland and various adrenal tumors. Tissue samples were obtained from 30 adrenocortical adenomas, nine adrenocortical adenocarcinomas, and 20 pheochromocytomas following laparoscopic surgery. Twenty normal adrenal glands were obtained from kidney surgical resection conducted due to renal cell carcinomas. USP10 expression was investigated on protein levels using immunohistochemistry and on mRNA levels using bioinformatics analysis in the Gene Expression Omnibus (GEO) Datasets. In the 20 cases of normal adrenal glands analyzed, USP10 protein was constantly expressed in situ in the cortex of the adrenal glands, but in the medulla of the gland, only the sustentacular cells were detected positive. In adrenal tumors, detectable levels of USP10 protein were found in 100 % (30/30) adrenocortical adenomas, 88.89 % (8/9) adrenocortical carcinomas, and 10 % (2/20) pheochromocytomas. Bioinformatics analysis did not show a significant difference in USP10 messenger RNA (mRNA) expression between adrenal tumors and normal adrenal gland tissues. A positive USP10 immunoreaction can be useful in distinguishing adrenal cortical tumors from pheochromocytoma.

MEN1 syndrome: an anusual case

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant endocrine disorder and is characterised by the concurrent appearance of adenomas of the parathyroid glands, neuroendocrine-enteropancreatic tumours, and pituitary adenomas, as well as other types of less frequent tumours, such as adrenal cortical tumours, carcinoid tumours, lipomas, etc. Two different forms, familial and sporadic, have been described. The gene responsible, MEN1, consists of 10 exons encoding a 610-amino acid protein known as menin. The MEN1 syndrome is caused by inactivating mutations in MEN1 tumour suppressor gene. The combination of clinical and genetic investigation helps in the diagnosis. Genetic testing has been advocated to identify MEN1 carriers of the MEN1 families for the purpose of earlier detection of tumours. We present a patient with traditionally described manifestations of MEN1 (a parathyroid hyperplasia associated with a pancreatic neuroendocrine tumour and a gastrinoma), but with a negative genetic test for the MEN1 mutation.

Adrenocortical tumor in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Adrenocortical tumour have been described in patients with 21-hydroxylase deficiency. These tumours are usually considered to be ACTH – dependent, as diffuse adrenal cortical hyperplasia is commonly seen. We report adrenal cortical tissue tumours developed in three patients with untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. All of them had symptoms of adrenogenital vililizing syndrome. A diagnosis of adrenocortical tumour was established by the symptoms, hormonal profile, ultrasonography, and adrenal CT scan. Two of the tumours were located in the right side, all the patients were performed surgery before hormonal replacement therapy because of evidence of secreated adrenal tumors, and the histological diagnosis indicated an adrenocortical adenoma. After removal of tumours, the size of adrenal gland was monitored by serial ultrasonography, and the congenital adrenal hyperplasia was confirmed by extremely high levels of basal serum testosterone, 17-OHP levels, increasing virilizing syndrome after surgery, diffuse hyperplasia of adrenal gland and identified mutations in CYP21A2 gene.

Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker.

Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma (ACC), is a challenge in surgical pathology due to its relative rarity and histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We characterized a cohort of human ACC and ACA, including a molecular screen, with a goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC underwent histologic and clinical review. In the 31 ACC cases with available material and a cohort of 10 ACA cases, a multiplex nucleotide amplification molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs demonstrated a wide variety of clinical and histologic characteristics with overall poor but unpredictable survival for subjects with ACC. By mutational screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type for all tested loci; and 1 case demonstrated repeated assay failures. Two of the 10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no additional mutations. Immunohistochemistry for beta-catenin was performed and compared with the results of the molecular screen. Strong nuclear beta-catenin immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in 10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong membranous staining by immunohistochemistry. Seventeen of the 18 cases without CTNNB1 mutation showed membranous staining or did not stain (94% specificity); the mismatched case demonstrated scattered (<10%) positive nuclei. Both mutations in ACA were corroborated with immunohistochemistry for beta-catenin. No histomorphologic parameter appeared dominant in lesions with a particular mutational status. Based on these results, mutational status of CTNNB1 in adrenal cortical neoplasms can be predicted with reasonable accuracy by immunohistochemical cellular localization. Nuclear localization of beta-catenin by immunostain may be helpful in analysis of select lesions of the adrenal cortex whose biological behavior is uncertain from clinical and histologic information; a larger cohort is required to test this hypothesis.

Immunohistochemical distinction of metastases of renal cell carcinoma to the adrenal from primary adrenal nodules, including oncocytic tumor.

Metastases of clear cell renal cell carcinoma to the adrenal can mimic primary adrenal cortical neoplasms or normal adrenal, especially in biopsy material. We compared 34 cases of clear cell renal cell carcinoma metastasis to the adrenal with 49 primary adrenal lesions (16 carcinoma, 22 adenoma, 9 oncocytic tumor, and 2 hyperplasia). Normal adrenal was available in 59 cases. Each entity was represented on tissue microarrays by duplicate-triplicate evaluable spots taken from spatially separate areas. Two pathologists evaluated all reactivity from 0 to 3+. A panel of 12 immunohistochemical stains was performed, including the first diagnostic uses of steroid receptor coactivator (SRC1) and equilibrative nucleoside transporter 1 (ENT1). The most sensitive and specific renal cell carcinoma markers were membranous reactivity for carbonic anhydrase IX (CAIX) and RCC marker and nuclear reactivity for PAX8. For adrenal cortical carcinomas, best markers were synaptophysin, SRC1, and MelanA; and for adrenal oncocytic tumor, synaptophysin and ENT1. Optimal markers for adrenal cortical adenoma and normal adrenal were ENT1 (more specific) and either MelanA or SRC1 (more sensitive). Calretinin, cytokeratin 34βE12 and CAM5.2, inhibin, and steroidogenic factor 1 (SF1) proved less valuable to the panel. Nonspecific cytoplasmic biotin reactivity was frequent for CAIX and PAX8. Tumors with high-grade cytology should be worked up with 2 of the 3 stains: CAIX, PAX8, or RCC marker; and either SRC1 or MelanA. Adrenal adenoma, or normal adrenal, versus low-grade renal cell carcinoma are distinguished by a panel of: CAIX, PAX8, or RCC Marker; ENT1 and either SRC1 or MelanA.

Adrenal imaging (Part 1): Imaging techniques and primary cortical lesions.

Adrenal glands can be affected by a variety of lesions. Adrenal lesions can either be primary, of adrenal origin, or secondary to other pathologies. Primary adrenal lesions can further be either of cortical or medullary origin. Functioning adrenal lesions can also give clues to the histologic diagnosis and direct workup. Over the years, various imaging techniques have been developed that have increased diagnostic accuracy and helped in better characterization of adrenal lesions non-invasively. In the first part of the two part series, we review adrenal imaging techniques and adrenal cortical tumors such as adenomas, adrenocortical tumors, adrenal hyperplasia and oncocytomas.

Risk of adrenocortical carcinoma in adrenal tumours greater than 8 cm.

Adrenocortical cancer (ACC) is a rare malignancy. In the absence of metastatic disease, the suspicion of ACC is based on size and radiological appearance. The aim of this study was to analyse the long-term outcome of patients with large adrenal cortical tumours (>8 cm). A prospective database recorded clinical, biochemical, operative and histological data on patients operated for cortical adrenal tumours between January 2000 and February 2013. Out of 130 patients operated for cortical adrenal tumours, analysis was restricted to 37 cortical tumours >8 cm. There were 31 (84 %) ACCs and 6 (16 %) benign adenomas (p < 0.01). The most common presentation was that of an abdominal mass [17 (55 %) vs. 3 (50 %), ACC vs. benign, respectively]. There was no difference in size between stage II and stage III-IV tumours; however, there was a trend for tumours to be heavier in advanced stages (920 ± 756 vs. 1,435 ± 1,022 g, p = 0.08, stage II vs. stage III-IV, respectively). No mortality was observed in patients with benign tumours during a median follow-up of 70 months (range 36-99 months). Mortality in the ACC group occurred in 17/31 (55 %) patients. Mitotane was administered in 12 (71 %) patients with stage III-IV ACCs with a 5-year survival rate 25 % compared to 20 % in patients who did not receive Mitotane. In stage II ACC, eight (57 %) patients received Mitotane with a 50 % mortality at 5 years. The high incidence of ACC in cortical tumours >8 cm underlines the need for adequate surgical resection via open surgery aiming to avoid local recurrence. Beyond surgery, the impact of other therapies is not fully characterised and the efficacy of adjuvant Mitotane treatment is yet to be proven.

Value of Calretinin Immunostaining in Diagnostic Pathology

Calretinin is a member of the EF-hand family of calcium-binding proteins. Because its expression is highly restricted to mesotheliomas, calretinin is, at present, the most commonly used positive mesothelioma marker that is most often recommended to be included in the various immunohistochemical panels used to assist in the differential diagnosis of these tumors. Calretinin expression has also been reported to be commonly expressed in a wide variety of other neoplasms, including sex cord-stromal tumors, adrenal cortical neoplasms, olfactory neuroblastomas, Schwann cell tumors, cardiac myxomas, and ameloblastomas. This article reviews the information that is currently available on calretinin expression in tumors and on its application as an immunohistochemical marker in diagnostic pathology.

Distinguishing cystic degeneration from other aging lesions in the adrenal cortex of Sprague-Dawley rats.

Cystic degeneration of the adrenal cortex is a common age-related finding in the Sprague-Dawley (SD) rat strain occurring more frequently in females. Compression of the adjacent cortex, a common hallmark of benign adrenal cortical tumors, often accompanies foci of cystic degeneration, creating a diagnostic challenge. Accurately differentiating these relatively common degenerative changes from proliferative lesions is critical in safety assessment studies. Cystic degeneration typically arises in the zona fasciculata of the adrenal cortex and often causes compression along the margin of the lesion. The degenerating cells are large, with abundant eosinophilic cytoplasm, or contain clear cytoplasmic vacuoles. Mitotic figures are generally uncommon. In many cases, cystic degeneration appears to arise in areas of hypertrophy in the zona fasciculata. In contrast, adrenal cortical hyperplasia and adrenal cortical adenoma are frequently comprised of smaller cells that cause compression of adjacent cortex, and in some cases mitotic figures are observed. Cytological detail and growth patterns should be considered more useful criteria than compression alone for separating degenerative cystic lesions from proliferative lesions in the adrenal cortex of SD rats.

Adrenal cortical carcinoma with extension into the inferior vena cava – case report and literature review

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an incidence rate of 1 to 2 per million person-years. ACC most commonly arises sporadically, but may be associated with familial tumour syndromes. Clinical symptoms are mainly related to an excess of steroid hormones. We present an unusual case of adrenocortical carcinoma in a 27-year-old male who complained of non specific mass-effect related symptoms of slowly growing intensity differing from others described in literature because of the patient’s age and the sudden deterioration of the clinical course. The tumour was resected with the left kidney with an extension into the inferior vena cava. Histological examination revealed morphological features characteristic of an adrenal cortical tumour. The immunohistochemical results (positive reactions for vimentin, CD56, inhibin, melan A, synaptophysin, bcl-2, calretinin) confirmed the diagnosis. According to the most widely used modified Weiss criteria and the Van Slooten system, a diagnosis of adrenal cortical carcinoma was strongly confirmed. The postoperative condition was poor. Reoperation was conducted, including abdominal aorta thrombectomy and aortic prosthesis implantation. The patient died two days after the second operation. Autopsy revealed a metastatic tumour in the left lung and morphological symptoms of acute circulatory collapse due to a massive haemorrhage into the abdominal cavity, which was the direct cause of death.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1602226377106882.

Perioperative anaesthetic management of a child with cushing’s syndrome for bilateral adrenalectomy

Nearly twenty five percent of the cases of cushing’s syndrome are due to adrenal hyperplasia without an ACTH secreting tumour. Twenty percent of patients with endogenous cushing have adrenocortical tumour about half of which are benign adenoma. Surgical intervention done due to failed medi cal therapy and in case of adrenal adenoma. A child aged 4½ years, weighting 29kg with features suggestive of cushing’s syndrome was admitted under paediatric surgery unit in Bangabandhu Sheikh Mujib Medical University. On investigation serum cortisol levels were raised. blood pressure was controlled by ACE inhibitor, calcium channel blocker and beta-blocker. He was scheduled for resection of adrenal cortical tumour. Electrolyte imbalance was corrected, steroid replacement was done. Patient was haemodynamically stable preoperatively.Surgery was completed unevenetfuly. Postoperatively patient was kept in ICU, ventilation maintained by control mode (CMV). After 24 hours the patient was extubated. When the patient found haemodynamically stable he was sent to the recovery room. DOI: http://dx.doi.org/10.3329/jbsa.v22i2.18148 Journal of BSA, 2009; 22(2): 84-87

Adrenal cortical neoplasms: a study of clinicopathological features related to epidermal growth factor receptor gene status

BackgroundAdrenocortical carcinoma (ACC) is a rare but highly malignant neoplasm with limited treatment options.MethodsIn this study, the clinicopathological features of 22 ACCs and 22 adrenocortical adenomas (ACA) were analyzed, and the EGFR protein expression, EGFR gene mutation status and EGFR gene copy number alteration of all tumors were examined using immunohistochemistry, fluorescence in situ hybridization (FISH), and the Scorpion Amplification Refractory Mutation System (ARMS), respectively.ResultsEGFR protein expression was detected in 63.6% of the ACC samples, and EGFR FISH was positive in 50% of the ACC samples (all were high polysomy on chromosome 7). In contrast, 27.3% of the ACA samples demonstrated EGFR expression, and none of the ACA samples tested positive by FISH. There were significant differences between the ACC and ACA in terms of protein expression (P = 0.035) and gene copy number alterations (P < 0.001).ConclusionsEGFR protein expression and high polysomy on chromosome 7 are frequent abnormalities in ACC than in ACA.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2068470757103500.

Pathology of the Adrenal Cortex: a Reappraisal of the Past 25 Years Focusing on Adrenal Cortical Tumors

A reappraisal of the major advances in the diagnostic pathology of adrenal cortical lesions and tumors in the last 25 years is presented, with special reference to the definition of malignancy in primary adrenal cancer and its variants. Slightly more than 25 years ago, Weiss proposed his diagnostic scoring system for adrenal cortical carcinoma. This represented a milestone for adrenal pathologists and the starting point for further modifications of the system, either through minor changes in the scoring procedure itself or concentrating on some particular Weiss criterion such as mitotic index, integrated into alternative scoring schemes or algorithms that are currently under validation. Improvements in diagnostic immunohistochemistry have led to the identification of markers of cortical origin, such as Melan-A, alpha-inhibin, and SF-1 and of prognostic factors in carcinoma, such as the Ki-67 proliferation index and SF-1 itself. With regard to hyperplastic conditions, genetic investigations have allowed the association of the majority of cases of primary pigmented nodular adrenocortical disease (PPNAD) in Carney complex to mutations in the gene encoding the regulatory subunit 1A of protein kinase A (PRKAR1A). Other hereditary conditions are also associated with adrenal cortical tumors, including the Li-Fraumeni, Beckwith-Wiedemann, Gardner, multiple endocrine neoplasia type 1, and neurofibromatosis type 1 syndromes. Moreover, several advances have been made in the knowledge of the molecular background of sporadic tumors, and a number of molecules/genes are of particular interest as potential diagnostic and prognostic biomarkers.

Adrenal cortical carcinoma presenting with secondary amyloidosis: A case report

Introduction: Adrenal cortical carcinoma is a rare aggressive tumor with a poor prognosis. Associated systemic amyloidosis is a rare phenomenon with only single case reported in English literature. case report: We report a case of a 50-year-old female harboring a huge adrenal cortical tumor along with systemic amyloidosis who underwent primary curative surgical resection of the tumor. Our patient had a Weiss score of 6 which is indicative of bad prognosis. conclusion: the presence of proteinuria in patients with adrenal cortical carcinoma may be indicative of amyloidosis. Further, the high risk of metastasis in adrenal cortical cancer mandates a close clinical follow-up.

An N-Ethyl-N-Nitrosourea Induced Corticotropin-Releasing Hormone Promoter Mutation Provides a Mouse Model for Endogenous Glucocorticoid Excess

Cushing's syndrome, which is characterized by excessive circulating glucocorticoid concentrations, may be due to ACTH-dependent or -independent causes that include anterior pituitary and adrenal cortical tumors, respectively. ACTH secretion is stimulated by CRH, and we report a mouse model for Cushing's syndrome due to an N-ethyl-N-nitrosourea (ENU) induced Crh mutation at −120 bp of the promoter region, which significantly increased luciferase reporter activity and was thus a gain-of-function mutation. Crh−120/+ mice, when compared with wild-type littermates, had obesity, muscle wasting, thin skin, hair loss, and elevated plasma and urinary concentrations of corticosterone. In addition, Crh−120/+ mice had hyperglycemia, hyperfructosaminemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia but normal adiponectin. Crh−120/+ mice also had low bone mineral density, hypercalcemia, hypercalciuria, and decreased concentrations of plasma PTH and osteocalcin. Bone histomorphometry revealed Crh−120/+ mice to have significant reductions in mineralizing surface area, mineral apposition, bone formation rates, osteoblast number, and the percentage of corticoendosteal bone covered by osteoblasts, which was accompanied by an increase in adipocytes in the bone marrow. Thus, a mouse model for Cushing's syndrome has been established, and this will help in further elucidating the pathophysiological effects of glucocorticoid excess and in evaluating treatments for corticosteroid-induced osteoporosis.

Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers

AimsTo determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs).Methods and resultsWe analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the Weiss system are all high-efficacy criteria for differentiating malignant from benign tumours (P < 0.001). MiR483-3p was overexpressed in 68% (17 of 25) of ACCs compared to 12% (three of 25) of ACAs (P < 0.05). Using a combination of miR483-3p and Smad4 improved diagnostic accuracy. Molecular markers were then tested in an independent set of 15 borderline tumours. We confirmed that the combined use of miR483-3p and Smad4 immunochemistry can complement the Weiss score in the diagnosis of ACC in cases that display borderline histology.ConclusionsTumour size, tumour weight, hormonal function and the Weiss system are useful clinicopathological criteria that can result in accurate diagnosis of most ACCs and ACAs. In challenging cases, miR483-3p and Smad4 expression may help in distinguishing these two entities.