Endocrine Abstracts

Activating mutations in the gene encoding β-catenin have been identified in the paediatric form of human craniopharyngioma (adamantinomatous craniopharyngioma, ACP), an aggressive pituitary tumour accounting for up to 10% of paediatric intracranial tumours. Recently, we generated an ACP mouse model and revealed that, as in human ACP, nucleocytoplasmic accumulation of β-catenin (βcat-nc) and over-activation of the Wnt/β-catenin pathway occurs only in very fe...

Octreoscan is currently the gold standard for diagnosis of somatostatin receptor positive NET but it is limited by a lower spatial resolution and physiological uptake noises. DOTATATE is a somatostatin analogue, radiolabelled with 68Ga and adapted for PET imaging.Aim of this study was to evaluate the diagnostic performance of 68Ga-DOTATATE PET compared to Octreoscan in NET.Fifty-one patients with NET (40 sporadic, 17 MEN1) of diffe...

Background: The pathogenesis of neural crest-derived tumours (phaeochromocytoma and neuroblastoma) is complex, and several studies applying functional genomics approaches have been performed in these tumours to date. However, the comparison of their genomic features has not been performed yet.Objective: We have carried out an in silico meta-analysis of altogether 1784 neuroblastoma and 351 phaeochromocytoma samples to establish similarities and differenc...

Introduction: The insulin-like growth factor-I receptor (IGF-IR) plays a key role in regulating growth, survival and invasion of several human malignancies including prostate cancer. In prostate cancer cells, the IGF-IR expression is upregulated by androgens through a nongenotropic signaling unresponsive to antiandrogens and requiring AMP-response element-binding protein (CREB) activation. This mechanism sensitizes cells to the proliferative and protumor effects of IGF-I. Metf...

Estrogen excess is a major contributing factor to the development and progression of post-menopausal Estrogen Receptor positive (ER+) breast cancers. Increased activity of aromatase, the enzyme that converts androgens to estrogens, and upregulation of its encoding gene CYP19A1 is often observed in breast adipose fibroblasts (BAFs) surrounding ER+ tumours. Understanding the process by which CYP19A1 is regulated between normal and diseased breast stroma may help to improve outco...

Background: Testicular germ cell tumours are the most frequent cancer of young men. While pathogenesis and reasons of an increasing incidence all over the world remain unknown, epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs), especially with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptor...

Differentiated thyroid cancers (DTC) have an excellent prognosis with a 10 year disease-related survival of 85%. However, about 5% of DTC patients develop an aggressive disease with distant metastasis and loss of radioactive iodine (RAI) avidity. An effective treatment is not available for these patients and survival rates are less than 15%. The MAP-kinase pathway is strikingly involved in the pathogenesis of DTC. This is why compounds striking the MAP-Kinase pathway may be us...

MEN1 germline mutations are identified in 70% of the familial forms of MEN1 and about 10%of the sporadic cases. Little is known about clinical differences between MEN1 with and without identification of MEN1 germline mutation particularly in terms of PA characteristics.Aim: To compare the clinical features of PA in MEN1 cases with and without germline MEN1 mutation and sporadic cases of PA. Patients and methods: Data were obtained in...

Hepatocellular carcinoma (HCC) is often diagnosed at late stage or metastatic condition. Surgical resection is considered treatment of choice and other treatment options include chemoembolization, radiofrequency ablation and photodynamic therapy. We evaluated the expression levels of the 5 somatostatin receptors (SSTRs) in 23 biopsies of HCC patients and also mTOR, p70S6K and 4eBP1 in HuH-7 and HepG2 and investigated the in vitro effect of somatostatin analogs (SA) and ...

Mitotane (o,p’DDD) is commonly used for the treatment of adrenocortical carcinoma (ACC), both for advanced disease and in the adjuvant setting. Mitotane induces adrenal insufficiency but specific effects on steroidogenic enzymes are unknown.We investigated 24-h urinary steroid metabolite excretion in ACC patients on adjuvant mitotane (AD) or mitotane for metastatic disease (MET). We compared samples collected before mitotane treatment (BEFORE; MET <...

Introduction: Bronchial carcinoids (BCs), originating from endocrine cells dispersed in the respiratory epithelium, can be divided into typical (TBC) and atypical (ABC). TBC are less aggressive, smaller, and much less likely to metastasize, while ABC are more aggressive and metastasize. mTOR has a central role in regulating cell growth, metabolism, and apoptosis. A differential mTOR activation in BCs has been previously demonstrated, suggesting that mTOR pathway might play a p...

Breast cancer remains the leading cause of cancer-related death in Australian women. Up to 70% of post-menopausal tumours are estrogen-receptor positive (ER+), dependent on estrogen for continued growth and proliferative advantage. Adjuvant anti-estrogen therapies are considered the cornerstone approach to the treatment of such tumours, and research is ongoing to maximize its effectiveness. The major source of estrogens for ER+ breast cancers is local conversion of androgen pr...

Mitotane (o,p’DDD) represents the most effective treatment of adrenocortical carcinoma (ACC). However, molecular mechanisms of mitotane action remain poorly understood. Mitochondrial (mt) impact of mitotane has previously been suggested but not yet fully validated. We investigated functional consequences of mitotane exposure on mitochondrial steroidogenesis, respiratory chain activity and biogenesis, using human adrenocortical secreting H295R and non-secreting SW13 cells....

Introduction: The pathogenesis of pituitary adenomas is incompletely understood. It was recently demonstrated that mutations in AIP, a novel tumor suppressor gene, are causing the familial isolated pituitary adenoma syndrome. Although initial data suggested that AIP mutations are rare in non-familial cases, a recent study demonstrated an increased prevalence in young sporadic macroadenoma patients.Aim: To perform a systematic screening of AIP mutations i...

Introduction: BC patients have a high prevalence of anti-TPO-autoantibodies (TPOAb), which seem to be protective in BC patients. We hypothesized the presence of T-lymphocytes citotoxicity against a common antigen between thyroid and BC cells.Aim: To evaluate the possible expression of TPO gene in BC.Materials: Frozen tissue specimens: 8 BC, 5 peri-tumoral breast tissues (PT), 3 pancreatic adenocarcinoma (P), 2 kidney cancers (K) an...

Introduction: Neuroendocrine tumors (NETs) over-express somatostatin receptors (SRs) and the efficacy of peptide receptor radionuclide therapy (PRRT) with somatostatin analogues labeled with high activities of β-emitting radioisotopes has been reported.Aim: Ongoing study to evaluate efficacy and toxicity of combination treatment with 4 cycles of radiolabeled DOTATATE, alternating 177Lu and 90Yin patients with metastasised NETs expressing SRs refract...

Context: Pathogenesis underlying non functioning pituitary adenoma (NFPA) formation and progression has not been well established. MEG3 is strongly expressed in the normal pituitary (NP) but not in NFPA derived from gonadotroph cells. High GSTP1 gene expression also seems to contribute to gonadotroph adenoma development. Recent reports indicate a role of miRNAs in the pituitary adenoma pathogenesis.Objective: To evaluate the expression of MEG3, DLK1, GST...

Objective: The role of surgery for recurrent adrenocortical carcinomas (ACC) is not well defined. Therefore, we evaluated the outcome after surgery for tumor recurrence in patients from the German ACC Registry.Methods: Only patients with first recurrence after initial R0 resection were investigated. Progression–free and overall survival (PFS, OS) after first recurrence were analyzed by Kaplan–Meier method. Cox proportional hazards regression mo...

Mutations in the AIP gene have been linked to familial cases of pituitary adenomas (Vierimaa et al, 2006). Analysis of the protein support its role as a tumour suppressor since mutations cause a loss-of-function with reduced protein interactions and over-expression of wild-type (WT) AIP reduces cell proliferation (Leontiou et al, 2008). AIP interacts with a number of interesting proteins, among them are the phosphodiesterases, PDE4A5 and PDE2A, the G proteins, Gαq and G&#...

Introduction: Extra adrenal paraganglioma (PGL) account for approximately 15% of all pheochromocytoma. Urinary bladder & mediastinum are rarest form of PGL. We present a case of bladder &Mediastinal PGL with a novel mutation in exon 1 of SDHB gene.Case Report: 18 years old male patient was admitted with five years episodic symptoms of headache, sweating, and palpitations, especially after urination. He also complained of postural dizziness for la...

Introduction: Insulinomas are the commonest hormone-secreting tumor of gastrointestinal tract. Presentation is usually insidious with neuroglycopenia and fasting hypoglycemia. Many patients do not report adrenergic symptoms of hypoglycemia and present with neurological or psychiatric manifestations that often lead to misdiagnosis. The symptoms of insulinoma lack specificity, including various seizure disorders, personality change, bizarre behavior, amnesia, convulsions, and in...

We describe a case of aggressive pituitary adenoma with atypical biological behavior treated with surgery radiation & chemotherapy. A 46 y/o F presented with nausea & acute vision loss R>L,with no symptoms of amenorrhea, hypothyroidism or hypoadrenalism. Brain MRI showed 4.7×3.6×3.6 cm pituitary macroadenoma with mass effect on optic chiasm, cavernous sinus extension, internal carotid artery encasement, extension into R foramen ovale, orbital apex, spheno...

Introduction: MEN-1 is a rare autosomal dominant familial cancer syndrome characterized by involvement of parathyroid glands, enteropancreatic endocrine tissues and anterior pituitary gland. This disease is linked to germline mutations in the MEN1 gene (more than 460 described), whose identification allows the familial genetic counselling. Here we describe a novel germinal mutation in exon 10 of the MEN1 gene identified in an Italian family.Case Report: ...

Introduction: Ectopic release of ACTH caused by pheochromocytoma is extremely rare. The clinical picture of hypercortisolism is overlapped by catecholamine excess that makes diagnosis more difficult.Case report: A 74-year-old women was admitted to the hospital because of hypertension, recently diagnosed diabetes and weight loss (10 kg per six months). In physical examination: cachexia, dehydratation, pallor, hirsutism, proximal muscle weakness, elevated ...

Serum gastrin (G) levels >1000 pg usually raise the suspicion for a neuroendocrine tumor (NET) secreting G. Rarely, such elevated G levels are seen in pts with pernicious anemia (PA) which most commonly is associated with autoimmune gastritis (AG) (1). AG can occur concomitantly with other autoimmune d/o incl. lymphocytic colitis (LC) (2). G stimulates enterochromaffin-like cells which increase histamine (H) secretion. H excess can cause diarrhea (D) as can bacterial overg...

Objective: To describe a patient with an unusual course of primary hyperparathyroidism (PHPT) due to parathyroid adenoma in 2004, who developed recurrent hyperparathyroidism due to parathyroid carcinoma in 2010, and a subsequent adenoma in 2011.To our knowledge, this sequential occurrence has not been previously reported in literature.Case: A 57-year old male was operated on for a parathyroid adenoma in the right inferior gland in 2004. He was asymptomat...

Introduction: Insulinomas are almost always located in the pancreas and are usually small. The peak incidence is from the third to fifth decade of life, with females being slightly more frequently affected. The average duration of neuroglycopenic symptoms prior to diagnosis is often prolonged, being more than 5 years in 20% of patients.Case presentation: Female, 52 years old, medical history notable for hypertension, dislipidemia and Graves disease. She ...

Introduction: The main therapeutic approach for non functioning pituitary adenomas (NFA) is surgery, since radiotherapy has several important side effects and medical therapy is rarely effective. Therefore, understanding the molecular pathways regulating NFA cell proliferation is crucial for future drug development. We here explore the possible role of mTOR inhibitors, Everolimus and BEZ235 (which also inhibits the PI3 K pathway) on the effects of Insulin-like Growth Factor-1 ...

Introduction: It has been demonstrated that mTOR inhibitors have potent anti-proliferative effects in a human Medullary Thyroid Carcinoma (MTC) cell lines. We here explore the possible role of mTOR inhibitors, Everolimus and BEZ235 (which also inhibits the PI3K pathway) on the effects of Insulin-like Growth Factor-1 (IGF-1) in human MTC primary cultures.Aims: To this purpose, 20 MTCs primary cultures, were treated without or with 1 uM Everolimus, 10 nM B...

Introduction: Pituitary adenomas account for 10–25% of all intracranial tumours. Although rarely malignant, they are associated with high morbidity due to severe endocrine effects and difficult surgical access. Alternative splicing (AS) consists in selective removal of non-coding regions from pre-mRNA and joining of coding regions to produce mRNA variants that may be further translated. AS is regulated by splicing factors and is often disturbed in cancer. AS of growth hor...

The effects in vitro and in vivo of somatostatin (SS) analogues are linked to the presence of specific binding sites on target cells. Estradiol (E2) may modulate the expression of SS receptors (SSTR) in some cell models, including breast cancer and pituitary cells. Aim of this study was to evaluate the effects of E2 on SSTR1-5 ligand binding domains (LBD) expression levels in prostate epithelial cells (PEC).Methods: We investigated the effe...

Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterized by the development of tumours of the parathyroid, anterior pituitary and pancreatic islets, etc. Heterozygous germ line mutations of MEN1 gene are responsible for the onset of MEN1. Here We reported totally 87 patients from 24 unrelated Chinese families associated with MEN1 and identified five novel mutations and several previously reported mutations. Furthermore, we detected a loss of het...

Primary hyperparathyroidism (pHPT) resulting from parathyroid tumours is a common endocrine disorder with incompletely understood etiology. In renal failure, secondary hyperparathyroidism (sHPT) occurs with multiple tumour development as a result of calcium and vitamin D regulatory disturbance.The aim of the study was to investigate whether HIC1 may act as a tumour suppressor in the parathyroid glands and whether deregulated expression involves epigeneti...

In our previous investigation on microRNAs expression pattern in parathyroid carcinomas (Ca), we detected the over-expression of microRNAs belonging to C19MC, the largest human cluster on chromosome 19q13.41. In the present study, the analysis of the expression of selected C19MC and the closely distal MIR371-3 clusters microRNAs (MIR512-3p, MIR517C, MIR520H and MIR372) was extended to 11 Ca, 24 adenomas (Ad) and 6 normal glands. The four microRNAs was expressed in 11% of parat...

Somatostatin analogues (SSA) represent a recognized therapeutic option in patients affected with functioning neuroendocrine tumors (NET). In non-functioning NET, SSA are reported to induce tumor stabilization in most of cases and objective response in <5%. NET associated to Multiple Endocrine Neoplasia type 1 (MEN1) are inherited tumors, generally located in the duodeno-pancreatic trait, characterized by well differentiated histotype, high expression of somatostatin recept...

Introduction: The isoform A of the human insulin receptor (IR-A) binds insulin with high affinity, and binds IGF-II with a 3–10 folds lower affinity. Cells lacking the insulin-like Growth Factor-I receptor (IGF-IR) and overexpressing the human IR-A (R-/IR-A cells) respond to IGF-II with reduced metabolic effects but unaltered or increased mitogenesis as compared to insulin stimulation. We hypothesized that this altered ratio of metabolic-to-mitogenic effects of IGF-II in ...

A breakdown in stromal-epithelial interactions mediated by androgens is emerging as a key factor in prostate cancer (PCa) aetiology and progression. Currently however, we have limited knowledge of the mechanics of androgen and androgen receptor (AR) action in prostate stroma, or how dysfunction in that compartment contributes to the disease process.In this study, immunohistochemical analysis of 64 PCa samples revealed an inverse relationship between stro...

Sex Hormone-Binding Globulin (SHBG), the specific plasma carrier for sex steroids, interacts with cell membranes. In breast cancer cells, SHBG-cell interaction is closely related to estrogen-sensitivity and it is followed by a well-defined cascade of events. Soon after SHBG binding to cell membranes, cAMP accumulates in the breast cancer cells, activates PKA that in turn suppresses estradiol-induced ERK activation. ERK inhibition abolishes the anti-apoptotic effects of estradi...

Atypical parathyroid adenomas represent a subset of tumors with histological features worrisome for carcinoma (PC), such as trabecular growth, fibrous bands and increased mitotic activity without unequivocal criteria of malignancy (local recurrence and/or metastasis). The question of whether these lesions might represent an anticipation of an aggressive clinical behavior that overtime may acquire the full blown features of malignancy remains to be established.<p class="abs...

Introduction: Pheochromocytomas are characterized by a high attenuation value on unenhanced computed tomography (CT). It is not known whether pheochromocytoma can be outruled as a cause of adrenal incidentalomas based on unenhanced attenuation values only. We evaluated the outcome of routine biochemical screening for pheochromocytoma in a series of patients with adrenal incidentalomas in relationship to the unenhanced attenuation values on CT.Design and ...

Background: Germline mutations in SDHB, SDHC, and SDHD cause hereditary phaeochromocytoma and paraganglioma (PGL) syndromes. The genotype-phenotype correlation of these mutations and relationship to penetrance is poor. Our objective was to assess characteristics of patients with SDH mutations seen in our dedicated multidisciplinary clinic.Methods: A retrospective observational study of patients attending from May 2005 to May 2010, approved as an institut...

Background: Refractory hypoglycemia in patients with metastatic insulinomas (RHMI) is an important cause of morbidity and mortality and everolimus could be a new therapeutic option.Methods: We conducted a restrospective multicentric study within the French group of endocrine tumors to evaluate the time to first symptomatic recurrence (TSR) in patients with RHMI after everolimus initiation. Ongoing hyperglycemic medical options and safety were recorded.</...

Recently, we investigated effects of the Tumor-VDA ASA404 in tumor models for neuroendocrine tumors of the gastroenteropancreatic system and adrenocortical carcinoma 24 hours after treatment of BON and NCIh295 tumor bearing mice with ASA404 (A), paclitaxel (P) or the combination (A+P). We detected for BON tumors extensive necrotic areas as well as a significant decrease in cell proliferation, increase of apoptotic cells and reduction of microvessels after A or A+P treatment wh...

Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers. In this study, we investigated the effectiveness of GHRH antagonist JMR-132 treatment in ovarian cancer cell lines (SKOV-3, CaOV-3 and OVCAR-3). Using MTT assay, we found that JMR-132 has a strong anti-proliferation effects on SKOV-3 and CaOV-3 cells in a time (0, 24 h, 48 h, 72 h, 96 h) and dose (0, 25 nM, 50 nM, 100 nM and 200 nM) dependent manner. Also, JMR...

This work focuses on the characterization of circulating tumor cells(CTCs) captured from the blood of cancer patients using a microfluidic chip functionalized with an antibody against the epithelial cell adhesion molecule (EPCAM). We visualize CTCs captured from the blood of prostate cancer patients taking advantage of the unique tumor-associated marker, prostate specific antigen (PSA). Our data demonstrate that CTCs are detectable preoperatively in patients with early stage, ...

Background: Actually mitotane is an adrenal-specific agent employed in the treatment of adrenocortical carcinoma (ACC), and although it has been used for several decades, its exact mechanism of action, remain to be fully elucidated. Some authors reported that mitotane affected in vitro the multidrug resistance gene mdr-1/P-glycoprotein. MRP1, belonging a multidrug resistance protein family, exerts a chemo-resistance activity in many type of cancer leading to the failure...

Studies into estrogen receptor alpha (ERα), progesterone receptor (PGR) and the androgen receptor (AR) involvement in breast, uterine and prostate cancers has provided considerable insight into the molecular actions these receptors, but have thus far focused on each receptor individually and alone in different cell types. Here, whole genome expression microarray analysis and ChIP-sequencing in ZR-75-1 breast cancer cells, in response to combinations of 17β-estradiol ...

Introduction: Peptide receptor radionuclide therapy (PRRT) is a treatment choice for inoperable or metastasized neuroendocrine tumours and this therapy seems more effective in the biochemical and volume control of disease than somatostatin analogues (SSA).Aims: To demonstrate the efficacy of medical therapy with SSA and PRRT in patients with well and moderately differentiated neuroendocrine tumours.Materials and methods: We evaluat...

Background: Currently, there is no satisfying treatment option other than gross total or subtotal resection in combination with adjuvant radiotherapy for the treatment of craniopharyngiomas. However, recurrence could occur in a substantial proportion of craniopharyngiomas despite gross total resection and radiotherapy. Human epidermal growth factor receptor 2 (HER-2/ErbB2) overexpression was determined in various human carcinomas and is associated with aggressive clinical beha...

Objectives: The Wnt-signalling pathway is involved in tumor development in various tissues. Wnt-signalling molecules are expressed in pancreatic beta-cells. In addition, Wnt-signalling regulates insulin secretion and the proliferation of pancreatic beta-cells in vitro and in animal models. However, it is not clear whether Wnts play a role for the development of human insulinomas. Therefore, we investigated the expression pattern of Wnt-signalling molecules in benign and...

Introduction: In 2009 the Endocrine Society’s clinical practice guidelines for management of hypoglycemic disorders, confirming previous suggestions, have stated that the new cut-off of insulin for the diagnosis of insulinoma should be lowed to 3 μU/mL in presence of hypoglycemia (serum glucose ≤55 mg/dL). Moreover hypoglycemia in post-prandial status has been reported in insulinoma, alone or associated with fasting hypoglycemia. Finally preexisting diabetes me...

Background: The adrenolytic agent mitotane is widely used in the adjuvant treatment of adrenocortical cancer, but its mechanism of action including potential effects on mRNA expression is poorly elucidated.Objective: To examine mitotane-induced mRNA expression changes in the H295R adrenocortical cancer cell line.Methods: Various concentrations of mitotane in different treatment periods (24–120 h) have been tested in cell viabi...

Ouabain is a cardiotonic steroid belonging to Strophanthus species. Recently its role in the treatment of tumors has been investigated, as ouabain seems to exert antiproliferative effects. Adrenocortical carcinoma (ACC) is a rare cancer, with poor prognosis, of which SW13 and H295R cells could be considered a cellular model.Our aim was to evaluate if ouabain exerts anticancer property.The effects of ouabain were assessed by MTT ass...

Introduction: There is scarcity of information regarding the profile of patients with Pheochromocytoma and paraganglioma from India.Aim: To study clinical profile of patients with Pheochromocytoma (PHEO)/Paraganglioma (PGL) attending the AIIMS hospital.Methodology:: Study protocol was approved by the AIIMS ethics committee. Written informed consent was taken from patients (parents in case of children). Patients of PHEO & PGL at...

In recent years, it was demonstrated that tumor infiltrating and circulating regulatory and cytotoxic T-cells are associated with clinical outcome in several solid tumors. However, their role in adrenocortical carcinoma (ACC) was never studied, although 60% of these tumors secrete autonomously cortisol, a well-established potent immunosuppressant that most likely influences the balance between different T-cells.Firstly, we analyzed the circulating regula...

Introduction: Parathyroidectomy is performed in primary hyperparathyroidism using either focussed approach or bilateral neck exploration depending upon the pre-operative localisation results. The type of localising investigations and utility of intra-operative adjuncts like IOPTH vary in individual units. In our unit, parathyroid sestamibi scan and neck ultrasound (USS) are done routinely for all cases, and SPECT/CT and CT or MRI are reserved for selective patients. This study...

Cancer cells have shown an overexpressed fructose transporter GLUT5 and preferential utilization of fructose as compared to glucose, implicating that a fructose-based analogue would be a useful target for diagnosis and treatment of cancer. We have successfully synthesized the fructose conjugated-gefitinib compounds {N-[4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxy-quinazolin-6-yl]-4- [N-methyl-N-(1-deoxy-1-fructosyl)]aminobutanamide}, and examined its antitumor effic...

Introduction: The efficacy and exceptionally good tolerance of estrogen blockade in the treatment of breast cancer is well recognized. Acolbifene (ACOL) is a novel and unique completely free of estrogen-like activity in both the mammary gland and uterus. In theory, this new antiestrogen represents a unique opportunity for a highly potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues (se...

Background: Gonadotropin-releasing hormone (GnRH) receptor is a G protein-coupled receptor involved in the synthesis and release of pituitary gonadotropins. GnRH analogs constitute the most widely employed medical treatment for prostatic cancer. The predominant mechanism of action is presumed to be via the inhibition of gonadotropins and resultant decrease in androgen. Although pituitary and extra-pituitary GnRH-R transcripts appear identical, their functional characteristics ...

Rationale and aims: Aberrant activation or “reactivation” of androgen receptor in the course of androgen-ablation therapy shows a potential cause for the development of castration-resistant prostate cancer. This study tested the hypothesis that belinostat (PXD101), a potent pan histone deacetylase inhibitor, may potentiate hormonal therapy and prevent onset of castration resistant phenotype Material and Methods. A panel of human prostate cancer (Pca) cells with grade...

Multiple endocrine neoplasia type 1 (MEN1) is a relatively rare autosomal dominantly inherited condition characterized by hyperplastic and neoplastic disorders of endocrine organs such as the parathyroid, anterior pituitary and gastroenteropancreatic endocrine tissues. Germline mutation of the causative gene, MEN1, which localizes to human chromosome 11q13 and encodes the 610 amino-acid nuclear protein menin, can be identified in most affected subjects. MEN1 gene mutation anal...

Introduction: miR143 and 145 seem to be involved in the pathogenesis of cortitotrophinomas by modulating the expression of MAPK7 and CCNL1 genes, which protein products are involved in cell proliferation, differentiation, and cell cycle progression. Objective: To analyze the modulation of miR-143 and -145 in the expression of MAPK7 and CCNL1 genes in corticotrophinomas and corticotrophic tumoral lineage (AtT20).Material and Methods: The expression of MAP...

Tc- 99m Sestamibi parathyroid scan (SP scan) is performed to identify location of either hyperplastic or adenomatous gland(s) in primary hyperparathyroidism (HPT). In this study we evaluated diagnostic outcome in 55 consecutive patients with clinical diagnosis of HPT who were referred for SP scans and subsequently had parathyroid surgery. These patients with HPT were of 66.9+12.46 (mean + SD) age, and had serum calcium 10.9+0.93 mg/dl, phosphorus 3.0+0.51 mg/dl, chloride 107+3...

Background: The prostate cancer (CaP) is among the most commonly diagnosed cancers, accounting for about 20% of all newly diagnosed cancers. Subject of recent studies is the role of vitamin D in the pathogenesis of CaP. Literature data speculated about the role of vitamin D in the progression of Cap. In addition, several studies have shown an association between VDR gene polymorphism FokI and CaP especially in the Asian population.Objective: The aim of t...

Progesterone (PRG) deficiency has been linked to an increased risk of cancer, while normal levels of PRG in the body actually help protect you against some forms of cancer. The tumor suppressor role of this steroid was envisaged, however the mechanism through which this occurs was not clearly established. The effects of progesterone act via the progesterone receptor (PR) of which two isoforms, called A (PR-A) and B (PR-B) were discovered. Herein, we present a novel finding sin...

More than half of patients with multiple endocrine neoplasia type 1 (MEN1) develop gastroenteropancreatic neuroendocrine tumors (GEPNETs). Among GEPNETs in MEN1, insulinoma is the second common functioning tumor and often diagnosed by its pathognomonic clinical feature, i.e. hypoglycemia. Compared to other functioning and nonfunctioning GEPNETs in MEN1, insulinoma is known to develop in younger age. We have recently constructed a database of Japanese patients with MEN1 and her...

Introduction: The genetic basis of multiple endocrine neoplasia type 1 (MEN-1) syndrome is often represented by inactivating mutations of Men-1 gene, found in 50–80% of different series. Recently, other mutations of genes encoding for the CDKI complex (p15, p18, p21, and p27) and of the AIP gene have been described in a small number of Men-1-negative patients.Methods and results: Since 2002 we tested for Men-1 mutations 16 patients born and living i...

Introduction: Pheochromocytoma (PHEO) is a rare tumor of chromaffin cells with variable clinical presentation. Adrenal PHEOs secrete excessive amounts of noradrenaline or of noradrenaline plus adrenaline, whereas extra-adrenal PHEOs (paragangliomas) mostly secrete noradrenaline alone due to lack of expression of phenylethanolamine-N-methyltransferase (PNMT), the key enzyme converting noradrenaline into adrenaline. We report two exceptional cases of paragangliomas responsible f...

Aim of the study: Presenting the changes in surgical management and patients’ characteristics based on a single-center data.Material and method: From 29/10/1997 to 31/04/2011 824 adrenalectomies were carried out, 641 (78%) laparoroscopic and 183 (22%) open. In all cases of laparoscopic adrenalectomy (LA) lateral transabdominal approach was used. Bilateral simultaneous adrenalectomy with the changing patient position was performed for bilateral pheoc...

Introduction: Follicle stimulating hormone receptors (FSHR) are physiologically expressed in gonads. FSHR are also expressed in gonadal cancers, but nothing is known on FSHR appearance in non-gonadal endocrine tumors. The present paper reports on the immunohistochemical detection of FSHR in pituitary, thyroid, adrenal and neuroendocrine tumors (NET).Materials and methods: The study included samples of 80 endocrine tumors (28 pituitary adenomas, 7 thyroid...

Tumour-associated myofibroblasts are activated fibroblasts known to influence many aspects of tumour development. Parathyroid tumours show increased microvessels and atypical/malignant tumours are characterized by fibrous bands suggesting activation of the stromal cells. The aim of the present study was to investigate the role of myofibroblasts in parathyroid tumorigenesis. Human parathyroid tissues were analysed by specific immunostaining for the myofibroblast marker alpha-sm...

Introduction: Neuroendocrine neoplasms are rare and multiform requiring a multidisciplinary approach. We report the experience of a Neuroendocrine tumor board (TB) established at our University Hospital.Aims: The aim is to share clinical and diagnostic data for best decision-making according to the existing ENETS guidelines.Materials and methods: According to the indications for ENETS Centers of Excellence, meetings with experts in...

Objective: Primary aldosteronism (PA) is a common cause of secondary hypertension. Antihypertensive agents interfere with the renin-angiotensin-aldosterone axis, and screening with the aldosterone to renin ratio (ARR) is preferably made without medication. Withdrawal may however be harmful. We examined the detection rate of PA in hypertensive patients taking their prescribed medication, apart from amiloride and spironolactone.Design and setting: Hyperten...

Aim of the study: To test B-Lymphocyte Stimulator (BLyS) as a new serological marker in the follow-up of patients with neuroendocrine tumors (NET).Methods: Eighty-one consecutive patients with NET and 56 age and sex-matched controls were enrolled in the study. According to the clinical course, patients were classified in 2 subgroups: evidence of persistent but stable disease or in remission (n=45) and patients with evidence of recurrent disease (p...

Introduction: Medullary thyroid carcinoma (MTC) and C cell hyperplasia (CCH) have a variable clinical presentation and prognosis and few data are available on the correlation between immunohistochemical characterization (IIC) and clinical behavior.Aim: We studied the clinical and morphological characterization of CCH and MTC and we evaluated IIC expression of PTTG-1, SSTR2A, VEGFR-1, VEGFR-2 and VEGFR-3 in 23 cases of CCH and/or MTC, correlating it with ...

We hypothesized that hormonal therapy favors the development of the hormone-resistant (HR) phenotype through epigenetic mechanisms. Human prostate cancer (Pca) tissues and in vitro and in vivo models were used to verify this hypothesis. We demonstrated that tumor cells continuously treated with BCLT or cultured in androgen depleted medium progressively acquire higher DNMT activity and expression. Increased DNMT expression and activity also paralleled the up-regul...

Antagonists of growth hormone-releasing hormone (GHRH-ant) may exert their antiproliferative effects directly on cancer cells, which are mediated by the tumoral GHRH receptors identified by us. Furthermore we showed that GHRH-ant are able to induce apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway. However, the molecular features involved in the antiproliferative effect of GHRH-ant have not yet been elucidated. To study this, gene expression profi...

Background: Patients with an insulinoma are at variable risk of severe hypoglycemia due to wide ranges of both tumoral insulin secretion and peripheral tissue sensitivity to chronic hyperinsulinaemia.Objectives: In this study we investigated the clinical, biological and tumoral characteristics of a large series of patients with immunohistochemically confirmed insulinoma and we assessed both insulin sensitivity and beta-cell function in fasting steady-sta...

Background: Riedel’s thyroiditis (RT) is a rare thyroid disease. Clinical and citological differential diagnosis with thyroid malignancy is difficult pre-operatively and often only pathological report may confirm the diagnosis.Methods: We report a case of a 72-year-old Italian woman with a known history of goiter, which showed a rapid increase in size at ultrasound check, suggesting malignancy. Based on non-diagnostic cytology (Thy 1), a total thyro...

Prolactin-secreting (PRL) adenomas are about 40% of all pituitary adenomas. The most important clinical symptoms of PRL excess are gonadal and sexual dysfunction as a result of tumor expansion in patients with macroadenomas. Medical therapy of prolactinomas relies on the use of dopamine agonists which induce normalization of PRL levels and shrinkage of the tumor mass in the majority of patients. The present study evaluated whether doses of dopamine agonist inducing normalizati...

The purpose of the present study was to elucidate expressions of ERβ1 and ERβ2 expression in papillary thyroid cancer (PTC). ER β splicing variants expressions were examined on formalin-fixed, paraffin-embedded thyroid tissues from 106 PTCs and 30 nodular thyroid goiters (NTGs) by immunehistochemical methods using Elivision plus two-step system. There was significant difference in the subcellular localization of ERβ1 expression (P<0.001), but not...

It is well established that oestrogens participate in the control of normal spermatogenesis and endogenous or environmental oestrogens are involved in pathological germ cell proliferation including testicular germ cell tumours. The effects of oestrogen are now known to be mediated by oestrogen receptor-α (ERα) and ERβ subtypes, but only ERβ has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, emb...

Introduction: Primary lymphomas of the endocrine glands are extremely rare entities. We retrospectively evaluated the clinical profile and the patterns of outcome among patients who were treated in our center with the diagnosis of high-grade B-cell primary endocrine lymphomas.Methods: Between May 1980 and August 2010, 450 patients were diagnosed as extranodal non Hodgkin Lymphomas (NHLs). Among them, 18 cases (4%) were primary testicular lymphomas (PTLs)...

Background: Chromogranin A (CgA) is essential for the formation of secretory granules and sequestration of hormones in neuroendocrine cells. Measurement of CgA levels is included in the diagnostic procedure of neuroendocrine tumors and pheochromocytoma. The aim of this study was to assess the reliability of the Kryptor assay for CgA measurement.Methods: Imprecision of the Kryptor CgA assay was determined with two levels of CgA concentration. Reference va...

Adrenal cortical carcinoma (ACC) is a rare malignancy, especially in children, and the annual worldwide incidence has been calculated as 0.3 cases per million children younger than 15 years old. We present a case of functioning ACC in a 7 years-old female child who manifested with virilization. She presented with low-pitched voice, excessive pubic hair growth, growth acceleration, clitoral enlargement and increased muscle strength at the age of six. Her blood pressure was norm...

Introduction: The adrenal glands are paired organs neuroendocrine, formed by the adrenal cortex and medulla, two distinct structures for histology, function, and embryological origin. The processes that most frequently affect the adrenals are adenomas 81.8%, 11.8% cysts, metastases, 11.8%, 5.9% carcinoma, pheochromocytoma 2.9%, 2.9% adrenalitis. 20–40% of adrenal masses are afuncionantes and/or discovered incidentally (incidentalomas) scans during abdominal imaging.<p...

Vitamin D receptor (VDR) and its ligand 1,25-Dihydroxyvitamin D3 (1,25OHD3) play, in general, an inhibitory role on the growth of normal and malignant cells. However, the mechanisms for this anti-proliferative action remain not completely understood. Recently, a 1,25OHD3-mediated effect on hormone production and steroidogenic genes has been reported in the human steroid-secreting adrenocortical cancer cell line NCI-H295R (Lundqvist J et al. 2010). The aim of this study ...

Multiple endocrine neoplasia type 2A (MEN2A) is an inherited syndrome caused by the mutation of RET gene. The classic variant of this syndrome includes the presence of medullary thyroid carcinoma (MTC), in association with pheochromocytoma and parathyroid neoplasia. MTC is usually the first presentation, with palpable neck mass and hypercalcitonemia, metastatic spread to local lymph nodes or distant sites.We report the case of a 41 year old Caucasian man...

Several studies have addressed the possible role of leptin, the product of the obesity gene (Ob), in ovarian cancer development and progression. Herein, we used the OVCAR-3 cell line expressed both the long (ObRb) and short (ObRt) isoforms of the mRNAs of the leptin receptor, to analyse the effect of leptin on the expression of selected genes involved in the cell cycle and apoptosis. OVCAR-3 cells were exposed to 2 and 20 ng/ml of leptin (noted in non-obese women) or 40 and 10...

With the development of medical imaging, many malignant lesions of the adrenal lodge are incidentally discovered. In this prospective monocentric study we are looking for factors of presumption of malignancy in the preoperative stage on a non-oncological series of 91 IS.Monocentric prospective study, AI revealed by TDM±echo supplemented by a clinic/hormonal adrenal exploration ±isotopic. In the absence of against indications, the indication of ...

Introduction: Pancreatic neuroendocrine tumors (PNET) are rare with an incidence of 3–4/1000,000. These tumors are non functional in 70–80% of the cases. The vast majority of them are differentiated neuroendocrine carcinoma. Distant metastasis detected frequently at the onset of diagnosis. Liver and lymph node metastases are the most frequent localizations. Cerebral, skeletal and pulmonary are not infrequent. Primary and metastatic small cell carcinomas with NE diffe...

Background: A number of studies have evaluated the association between prolactin (PRL) and breast cancer risk, but some results have been inconsistent.The aim of this study was to investigate, if the circadian rhythm of PRL was maintained in pre- and post-menopausal patients with breast cancer and if there is a correlation between serum PRL level, serum concentration of insulin-like growth factor 1 (IGF1), tumor staging and expression of estrogen, proges...

Introduction: Neuroendocrine lesions in the thyroid gland are uncommon. The differential diagnosis usually includes medullary thyroid carcinoma, paraganglioma and metastases. There are few non-conclusive reports of primary neuroendocrine carcinomas of the thyroid.Clinical case: A 49-year-old woman with a past medical history for familial hypercholesterolemia and right oophorectomy for mature teratoma with struma ovarii, was evaluated for a rapidly growin...

Background: Persons with CAH may be at increased risk of developing adrenal myelolipomas, particularly if their CAH is poorly controlled. Adrenal masses can be detected by ultrasound with high sensitivity and specificity. Contrast-enhanced ultrasound (CEUS) may be a useful method in the diagnostic work-up of adrenal mass with excellent sensitivity for the diagnosis of malignancy. However, ultrasound is not included in the diagnostic algorithm of patients with CAH.<p class=...

Introduction: MEN1 is characterized by tumors of parathyroid glands, pituitary and pancreas. Pituitary tumors frequently produce PRL and GH, but acromegaly due to ectopic GHRH secretion has been reported in <1% of cases. Here we present a case of two patients belonging to a MEN1 family (c.207delC; p.P69PfsX118 mutation (ENST00000377313), affected by primary hyperparathyroidism, in association with acromegaly due to ectopic GHRH secretion and bronchial carcinoid, respective...

A 66-year-old woman had no history of systemic diseases. She had developed watery diarrhea for 4 months initially, without abdominal pain, fever, any aggravating or relieving factor. She visited gastroenterologist, and colonoscopy showed only mixed hemorrhoid. Irritable bowel syndrome was impressed then. Thus, anti-spasmodics and anti-diarrheals were prescribed. However, diarrhea persisted for 1 year, and body weight loss of 7 kg occurred during this period of time. She later ...

Introduction: Pheochromocytomas are rare but treacherous catecholamine-producing tumors of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue. We refer a case with stabilization of tumor growth and hormonal improvements following repeated s.c. injections of octreotide.Case report: We report a female patient aged 35 with a finding of bilateral adrenal mass with sever cardiovascular symptomatology (f...

Adrenocortical carcinoma (ACC) is rare and aggressive malignancy with poor prognosis. Patients present with hormone excess or a local mass effect, or incidentally. ACC has undergone metastatic spread in 40–70% of patients at the time of diagnosis. Surgical removal is treatment of choice. Standard chemotherapy with mitotane has limited efficacy.The aim of this paper is to present the results of single tertiary center for diagnosis and treatment of AC...

Introduction: Leydig cell tumors are a type of steroid cell tumor, account for 0.1% of all ovarian tumors. The clinical presentation is usually a hyperandrogenic state with signs of virilisation. The tumor has a benign behavior, with an excellent prognosis and reversion of symptoms after surgical treatment.Case report: Woman, 81 years-old, nulliparus, with clinic hyperandrogenism and vaginal bleeding during the last year. She had history of dementia synd...

A 31-year-old man presented with a two month history of sweating, right-sided abdominal pain and supraclavicular swelling. CT scanning showed widespread lymphadenopathy with multiple retroperitoneal lymph nodes. Biopsy of a left supraclavicular node resulted in a diagnosis of metastatic paraganglioma. Raised urinary catecholamine as well as urinary metanephrine levels further confirmed the diagnosis.A normocytic anaemia requiring repeated blood transfusi...

Clinical caseIntroduction: Insulinoma is a rare disorder with an estimated incidence of 1 case per 250 000 people per year.Case report: 37 years old female, with a history of irritable bowel syndrome, dyslipidemia and kidney stones. In December 2010, she developed a headache, dizziness and visual disturbances, predominantly in the evening and amnesia for some of the episodes. Initially interpreted as peripheral vertiginous syndrome, because of recurrence...

Introduction: Among three types of gastric neuroendocrine tumors (GEPNETV) type 1 are most common. At the basis of the pathogenesis of type 1 is atrophic gastritis, which leads to achlorhydria and deficiency of intrinsic factor, resulting in G cell hyperplasia and hypergastrinaemia. Gastric endoscopy usually reveals the multiple and polypoid lesions (<1–2 cm) in the corpus. Five-year survival in these patients is not different from survival in the selected age group p...

Introduction: Multiple endocrine neoplasia type 1 syndrome (MEN1sy.) is a complex disease predisposing to a variety of multifocal neuroendocrine tumors (NET). Approximately 5% of pancreatic VIPomas and glucagonomas are associated with MEN1sy., most of them with metastases at diagnosis.Case report: A 15-year-old boy was admitted with primary hyperparathyroidism, pituitary microadenoma (6 mm) and suspected MEN1sy. His father had primary hyperparathyroidism...

Neuroendocrine tumors are rare in young patients and usually have favorable course. We present a case of young, 13-year-old girl diagnosed with insulinoma. The diagnosis was stated on the basis of the presence of neuroglycopenic symptoms. An abdominal CT scan demonstrated a tumor localized in the head of pancreas. The patient received diazoxide as a preparation to surgery. Therapy was effective, but discontinued due to side effects. Patient underwent the Whipple operation. Dur...

During the evaluation of hypercortisolism, distinction between Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) may be problematic. Detailed medical history, diagnostic procedures and pitfalls associated with EAS of four cases are presented. All the four patients had ectopic Cushing’s syndrome due to typical bronchial carcinoids. Their mean age was 39 years, and the mean time from the presentation of Cushing’s symptomes until diagnosis and definitive cure ...

Introduction: Insulinomas are the most common form of functioning pancreatic neuroendocrine tumors (NET) with an estimated incidence of 1–3/million per year. Less than 10% are malignant and rarely with distant metastases, carrying a poor prognosis.Case report: We report a case of a 73-years-old woman attended at our ER for recurrent syncope, with irrelevant medical history. Several radiology exams were preformed, revealing numerous liver metastases ...

Introduction: Mucinous ovarian cystoadenoma with stromal luteinization and hilar cell hyperplasia is a rare cause of hirsutism and virilization and only few cases are described in literature. We present a rare case of mucinous cystadenoma with hypertestosteronemia.A 38-years old woman came to our observation for severe hirsutism and oligomenorrhea. Hormonal work-up showed severe hypertestosteronemia (total testosterone: 4.39 ng/ml) with high levels of DH...

Introduction and objective: Neuroendocrine tumors (NETs) are relatively rare tumors. The majority are located in the gastrointestinal (GI) tract and bronchopulmonary system. The aim of this report is to study the characteristics of gastrointestinal NETs at diagnosis.Material and methods: Descriptive study about 18 patients diagnosed of gastrointestinal NETs during 1993–2011 in our hospital. Data regarding demographic, clinical, analytical, anatomopa...

Objective: A prospective study to research the relationship between initial levels of prolactin in the development and outcome of patients with gestational trophoblastic disease.Material and method: A longitudinal study including 51 women attending the Reference Center of Gestational Trophoblastic Neoplasia of Rio de Janeiro- Brazil, with complete mole, and comproved histopatologic examination. All women were followed up until remission was achieved. The...

Background: A 27-years-old women affected by recurrent pheocromocytoma/paragangliomas. We describe the evolution of disease and the surgical approach. The patient underwent a two-steps bilateral adrenalectomy for pheocromocytoma. At 15 years she underwent a left adrenalectomy. At 19 a right adrenalectomy+removal of paracaval paraganglioma were performed. After 8 years of good health she experienced again headache, tachycardia and hypertension not responsive to therapy. A diagn...

A palpable parathyroid mass, in a patient with primary hyperparathyroidism, is presumed to be parathyroid carcinoma until proven otherwise, with other less common causes including parathyroid cysts and adenomas.In developing world primary hyperparathyroidism presented in different way not only in the disease age group as well as in clinical symptoms and signs. More cases of symptomatic PHPT are presented in younger age group and some time large adenomas ...

Insulinoma is a very rare type of islet cell tumor. The aim of our study is to report our clinical experience with insulinoma in order to determine clinical, biological, radiological and therapeutic particularities of this tumor type.It’s a retrospective study, including five patients (three women and two men) referred to our department between 2005 and 2011 for hypoglycemia exploration. Mean age of our group is 39.8±15.4 years (ranges: 20&#150...