Endocrine Abstracts

One of the important proangiogenic factors involved in the growth of normal and neoplastic tissues is vascular endothelial growth factor VEGF.Therefore we hypothesized, that serum VEGF concentration would differ between patients with metastatic and non-metastatic thyroid cancer, with multinodular goiter and healthy subjects. We also hypothesized that endogenous TSH stimulation would effect serum VEGF level. The study protocol was approved by the Ethical ...

The ‘Multiple Endocrine Neoplasia’ predominantly affect the pituitary gland, parathyroids, thyroids, adrenal glands and pancreas. We present the case of a patient with three different functioning endocrine gland tumours, but who cannot be included in any of these groups.Case report: Sixty-five-years-old female with recurrent episodes of nephritic colic and hypertension for 2 years; non-specific gastrointestinal complaints, hirsutism, hyp...

The aim of the study was to estimate the influence of a thyroid remnants’ volume, postsurgical concentration of thyroglobulin and radioiodine dose on the early treatment efficacy of well differentiated thyroid cancer.Material and methods: We retrospectively analyzed 91 patients (76 females, 15 men) with well differentiated thyroid cancer.Results: Histological classification revealed 68.1% (62/91) papillary thyroid cancers, 25....

Purpose: 111In-octreotide scinti aphy may be useful in patients with insulinoma during pre-surgical localization of the tumor and octreotide is effective in inhibiting insulin secretion and reducing the hypoglycemic events. The aim of the study was to evaluate 111in-octreotide scintigraphy in localizing primary and metastatic insulinomas and predicting the response to octreotide administration.Patients and methods: Diagnosis of insulinoma was made in 17 ...

Introduction: Schwannomas are benign, encapsulated, solitary, slow-growing tumors which originate from nerve sheath cells in cranial, periferic, symphathetic nerve system. Aproximately, 25–45% of schwannomas are in head and neck region. N. Vagus Schwannoma are seen relatively, rarely. The patients frequently apply with a slow-growing, painless servical mass. Malign transformation is unusual.Case report: The patient 37 years old applied to our clinic...

Aim: To access the efficiency of mulitispine computed tomography (MSCT) in ectopic ACTH-syndrome.Patients and methods: Five clinical cases (2 female and 3 male cases) with severe hypercortisolism were analyzed, age from 26 to 63 years old.Results: In all of the 5 cases there were significant reasons to suppose ectopic ACTH-syndrome: rapid development of clinical features (in 4 of 5 cases), loss of lean mass compound with rounded an...

The ability of local invasion and distant metastasis indicates malignancy. Focal adhesion complex plays an important role during cell invasion. This complex consists of integrins, focal adhesion kinase (FAK), vinculin, talin, α-actinin and paxillin. Activation of FAK regulates the assembly of focal adhesion and stress fiber formation via GTPase Rho and Rac, which is responsible for the migratory behavior of cells. In this study, we demonstrated the inhibitory effect of ro...

Type 1 iodothyronine deiodinase (D1) is responsible for the conversion of thyroxin (T4) into tri-iodothyronine (T3). The enzyme is mainly present in thyroid, liver and kidneys.There is strong evidence that the metabolism of thyroid hormones is disturbed in some neoplasmatic tissues. However there are only few available data about D1 enzymatic activity in liver tumors.The aim of this study was to estimate the e...

Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Parathyroid hormone-related protein (PTHrP) occurs in a high proportion of breast cancer and is strongly implicated in their metastatic spread to bone. Overexpression of PTHRP and its receptor in breast tumour cells could also promote the growth in an autocrine fashion. Signal transduction of growth factor receptor, EGFR (ErbB1, HER1) and ErbB2 (Neu, HER2) ...

FNH is the second most common benign liver tumor caused mainly by oral contraceptives. D1, which is a crucial enzyme in catalyzing prohormone thyroxine (T4) into active triiodothyronine (T3), is mainly present in such tissues as thyroid, liver and kidney. There are only few data about D1 enzymatic activity in neoplasmatic conditions. Mostly in tumors reduced D1 activity was found.The aim of the study was to examine the activity of t...

We present an unusual case of painful gynaecomastia due to a large adrenocortical tumour secreting oestradiol and other steroid hormones.A 46 years old man presented with a 6 months history of progressive, painful gynaecomastia. He had no other specific symptoms and had previously been well. Alcohol intake was not excessive. Interestingly, his sister had presented with a phaeochromocytoma 2 years previously.Examination demonstrated...

Multiple endocrine neoplasia type 1 (MEN1) is a rare dominantly inherited neoplastic syndrome. Tipically, it affects three major locations: parathyroid, endocrine pancreas or duodenum (GEP) and anterior pituitary. MEN1 is caused by mutations in MEN1 gene and its testing is now used as a complement to clinical diagnosis which may be hindered by the variable penetrance and expression of the defects. Mutation carriers are life-long monitored, while unaffected relatives can avoid ...

Background: Expression of somatostatin receptor (SST) and therapy with somatostatin analogues have been scarcely investigated in parathyroid tumors.Objective: To evaluate the effects of depot long acting octreotide (OCT-LAR) on primary hyperparathyroidism in patients affected with multiple endocrine neoplasia type 1 (MEN-1).Subjects and methods: Eight patients with a genetically confirmed MEN-1 were enrolled. All patients presented...

Carcinoma of the thyroid gland is an uncommon cancer but is the most common malignancy of the endocrine system. The treatment of the thyroid cancer includes surgery, radioactive iodine and hormone treatment. Postoperative hypothyroidism is the most common complication of thyroidectomy for thyroid cancer. After thyroidectomy, the patient takes a thyroid hormone drug (levothyroxine) in supresive dose for the rest of his life.In hypothyroidism there has bee...

Background: Parathyroid hormone-related protein (PTHrP) was discovered as a tumor product. It is also one of the complex epithelial and mesenchymal interaction signal mediator in breast development. An increase in the prevalence of malignancy in patients with Klinefelter’s syndrome, but not in patients with idiopathic gynecomastia has been previously reported. PTHrP may play a critical role in the development or progression of breast cancer.Aim: We ...

Context: Clinical studies are needed to classify rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC) into one of three clinical risk groups.Objective: We analyzed genotype–phenotype correlations associated with the RET protooncogene mutation R770Q in exon 13 which was detected simultaneously with a Y791N mutation in the same family.Results: Calcitonin determination in a 43-year-old female ...

Aim: To address the role of FDG/PET-CT in the follow-up of DTC.Methods: About 110 consecutive patients (86 female, 24 male, mean age 45±13 years), with DTC were selected between 1999 and 2006. All patients underwent total thyroidectomy, radioiodine ablation and had undetectable serum thyroglobulin (Tg) during L-T4 suppressive therapy and negative serum TgAb. The follow-up included a yearly clinical examination with n...

Poorly differentiated and anaplastic thyroid carcinomas are aggressive human cancers that are resistant to conventional therapy. DAC inhibitors (DACi) are a promising class of drugs, acting as anti-proliferative agents by inducing apoptosis and cell cycle arrest.Panobinostat (LBH589) is a potent DACi belonging to a structurally novel cinnamic hydroxamic acid class of compounds, able to inhibit the activity of different isoforms of HDACs (HDAC 1, 3–6...

AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) is an adenylate uridylate-rich elements (ARE) binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines and cell cycle regulatory genes. Several studies demonstrated AUF1 expression in kidneys, liver, lymphoid tissues and melanocytes, and its involvement in apoptosis, tumorigenesis and development by its interactions with AREs bearing...

Retinoic acid (RA) acts as an anti-proliferative and re-differentiation agent in the therapy of thyroid carcinoma but the molecular mechanisms by which RA mediates these effects are not well understood. We have investigated the effect of RA on the production and post-translational modification of the two ENO1 transcriptional products in the human follicular thyroid carcinoma cell line FTC-133. The single ENO1 transcript encodes a 48 kDa ENO1 with its unique N-terminal enolase ...

Introduction: The adrenal cortex is highly involved at the immune-neuroendocrine interface, and several cytokines are known to influence the proliferation, differentiation, apoptosis and hormone production of adrenocortical cells. We therefore hypothesized that immune mediators might be involved in adrenal tumorigenesis, as well. Gene expression patterns of various inflammatory and immune mediators were studied by a functional genomics/bioinformatics approach.<p class="abs...

Introduction: The pathogenesis of sporadic adrenocortical tumors is poorly elucidated. Considering the importance of the adrenal cortex at the immune-neuroendocrine interface and the known actions of immune mediators on adrenocortical cell functioning, we supposed that immune or inflammatory factors might be involved in the pathogenesis of these tumors. Gene expression patterns of various inflammatory and immune mediators were studied by a functional genomics/bioinformatics ap...

Introduction: Hipersecretion of somatotrophin axis hormones in acromegaly favours the development of numerous metabolic and organ complications. The aim of the study was to establish the occurrence integrity of these complications in acromegalics.Material and methods: The tested 72 acromegalics – 32 men aged 46.9±15.2 years and 40 women aged 58.8±12.0 years, for which the period of the illness was determined, the body mass index (BMI) and ...

The pattern of SSTRs expression in neuroendocrine neoplasms determines the possibility of the detection of the primary tumour and distant metastases, the application of radio-guided surgery (RGS) and the outcome of the treatment with itrium or lutetium labeled somatostatin analogues. The frequency and expression pattern of each subtype of SSTRs not only vary considerably in different NET but also in each patient.The aim of the study was to assess the SST...

Potassium bromate (KBrO3) is a known prooxidant and carcinogen. Melatonin is a highly effective antioxidant. Indole-3-propionic acid (IPA) – an indole substance, and propylothiouracil (PTU) – an antithyroid drug, also reveal some antioxidative effects. The aim of the study was to evaluate KBrO3-induced lipid peroxidation in vitro in tissues collected from either control or melatonin-treated rats, and to compare potential preventive effect...

The heterodimeric peptide hormone relaxin is involved in extracellular matrix turnover during development and lactational differentiation of the breast. Relaxin expression is increased in human breast cancer and serum relaxin levels in breast cancer patients were reported to correlate with metastatic disease. We have established relaxin over-expressing transfectants of the highly invasive estrogen receptor-negative human breast cancer cell line MDA-MB-231 (MDA/RLN) to investig...

The peptide growth factor relaxin (RLN) is expressed in human thyroid carcinoma cell lines and tissues. We have previously established thyroid carcinoma cell transfectants with over-expression of relaxin and demonstrated that relaxin increases cellular motility and in-vitro invasiveness in these transfectants. This increase in motility and migration is relaxin receptor (LGR7)-dependent. S100A4 (metastasin), a member of the S100 family of calcium binding proteins, is known to c...

Cyclic Cushing’s disease is a rare situation due to episodic hypersecretion of ACTH. Suspicion is raised when strong clinical stigmata occur, with normal basal values of cortisol and normal responses to dynamic tests. After performing several tests, particularly during phases without symptoms (well-being), the probability of successful diagnosis increases.We describe the case of a 33 years old female patient with full-blown clinical picture (weight ...

Introduction: Ganglioneuromas are rare, benign tumors of mature ganglion cells, arising from the sympathetic ganglia and 20% are located in the adrenal medulla, representing 1–4% of adrenal incidentalomas. About 1/3 secrete catecholamines but hypertension and other adrenergic symptoms are rare. About 60% are depicted with 131I- MIBG.Case report: A 72-year-old man was admitted for a left adrenal tumor 9×8 cm, incidentally found in abd...

GH-secreting and non-functioning pituitary tumors are clinically distinct, usually benign but potentially locally aggressive lesions originating from the replication of a single mutated pituitary cell. As for the underlying genetic and epigenetic alterations, also the patterns of activation of specific signaling pathways as well as the prognostic molecular factors leading to local invasiveness are, to date, largely unknown. In this study, we used two-dimensional electrophoresi...

Introduction: Multiple endocrine neoplasia type 2 (MEN2) and medullary thyroid carcinoma (MTC) are autosomal-dominant inherited diseases caused by germline mutations within the RET protooncogene. Until now, genetic testing for mutations of exon 10, 11, 13, 14, 15 and 16 was recommended for these patients (familial and sporadic cases) to identify disease-causing mutations. Because of a strong genotype–phenotype correlation in these diseases, early genetic testing of...

Introduction: Thyroglobulin (Tg) measurement is the cornerstone in the follow-up of DTC. Sensitivity can be optimised by measuring recombinant TSH stimulated Tg (rhTSH-Tg). Higher sensitivity results in more Tg positive patients who need imaging and considerable patient burden. We assessed the impact of rhTSH-Tg measurement on health related quality of life (HRQOL).Methods: In 121 patients in follow-up for DTC, Tg during thyroid hormone suppression thera...

Ectopic ACTH syndrome (EAS) occurs in around 10% of all cases with ACTH-dependent hypercortisolism. The mean age of clinical presentation varies from 45 to 50 years, and most of them caused by intrathoracic neoplasm, and recognition of the disorder may be delay. Subsequently, it may be difficult to locate the ACTH source and manage the patients’ hypercortisolism. We present our patients with EAS from 2000 to 2007. Four patients, aged 15–43 years, two females and two ...

Objective: Therapeutic options for patients with dedifferentiated thyroid carcinoma are rare and alternative treatment strategies are needed. Among the most promising new agents for these patients are protein kinase inhibitors like the BRAF- and multi-targeted kinase inhibitor sorafenib. We have already shown that sorafenib inhibits growth of dedifferentiated thyroid carcinoma cell lines with and without BRAF mutation. The purpose of this study was to analyze the molecular eff...

Background: The androgen-secreting tumors constitute fewer than 1% of ovarian tumors. Leydig cell tumor is one of the most common of this type of lesion and it is usually benign, small and unilateral.Case report: A 67-year-old women was referred to the Endocrine clinic due to hirsutism (score 22 Ferriman–Gallwey) and male type alopecia with 3 years of evolution and progressive worsening. Biochemically she had high levels of serum testosterone –...

This study examined whether different forms of hereditary pheochromocytoma are characterized by different catecholamine phenotypes and whether this is reflected by differences in plasma concentrations of normetanephrine, metanephrine and methoxytyramine – the respective O-methylated metabolites of norepinephrine, epinephrine and dopamine. Subjects included 154 patients with hereditary pheochromocytoma, 72 with tumors associated with von Hippel–Lindau (VHL) syndrome, ...

Background/aim: Vitamin D receptor (VDR) expression has been shown to be upregulated in several tumors and is thought to represent an important endogenous response to tumor progression. Therefore, in order to evaluate the role of VDR-gene and of the 25(OH)-Vitamin D3 in thyroid cancer we analysed four polymorphisms in patients with thyroid cancer and healthy controls.Patients and methods: Patients (n=136; 84 females and 52 males) with d...

Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and no established therapy in advanced stage. Cisplatin is the most frequently used cytotoxic drug, but even combined with doxorubicin and etoposid, the response rate is <50%. Recently, it has been demonstrated that the excision repair cross complementing group 1 (ERCC1) plays a relevant role in the DNA repairing process, particularly in the correction of platinum-induced DNA adducts. Accordingly, ERCC...

Introduction: Prostate cancer (PCa) progression is known to depend on various hormones and growth factors, but their role and underlying molecular mechanisms remain poorly understood. We recently presented preliminary findings indicating that leptin causes a greater level of activation of the JAK2/STAT3 and MAPK (ERK1/2) pathways, as well as transactivation of HER2, in androgen-sensitive LNCaP cells than in androgen-insensitive PC3 and DU145 human PCa cell lines. We and others...

Adrenocortical carcinoma is a rare tumor characterized aggressive growth and poor prognosis. This tumor requires the complex way of treatment, where basic method is surgery.The aim of this study was to evaluate the long-term outcome and role of surgery in patients with adrenocortical carcinoma.Methods: From 1998 to 2007, 44 patients were operated for adrenocortical carcinoma (14 cortisol-secreting tumors, 1 virilizing tumor and 29 ...

Adrenocortical tumor (ACT) is a rare, heterogeneous malignancy whose pathogenesis is unclear. The oncoprotein PTHrP, found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the receptor PTH-R1. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinoma (ACC), 13 adrenocortical adenoma (ACA), and investigated the effects of PTHrP (1–34) on H295R c...

Even after complete resection, patients with ACC have a high risk of relapse, and adjuvant treatment with mitotane is frequently recommended. Although mitotane has significant efficacy in this setting, it is associated with a wide range of side effects. As survival is highly variable, prognostic factors are of great interest to better guide adjuvant therapy after radical resection.We analyzed clinical and histopathological data of patients without distan...

Aim: The aim of multi-center, observational study was to assess the outcome of the treatment with somatostatin analogue octreotide-LAR (O-LAR) patients with acromegaly.Material: Material consisted of 360 patients (60% women) aged 18–84 years (mean 45.5; S.D.±12.9) with active acromegaly. Prior to the inclusion 172 patients underwent unsuccessful neurosurgery.Methods: Observation was planned for 1 year. O-LA...

We studied the practice of investigations for diagnosing and localising insulinoma in our hospital. We looked at the number of investigations performed before exact localisation of insulinoma.We identified 5 cases that were confirmed on clinical, biochemical or histopathological bases and were recorded on the histopathology and IT database as ‘insulinoma’ from 1986 to 2004. We looked retrospectively at the case notes of these cases.<p class...

Pituitary tumours may be more prevalent than previously appreciated. Although this is thought to relate mostly to greater utilisation of imaging techniques in recent years, evidence suggests that the increased prevalence also applies to clinically important tumours.We have created a nationwide registry of pituitary tumours occurring in Iceland for the last 55 years. We have examined medical, surgical, pathology and imaging records at all hospitals as wel...

Bronchopulmonary endocrine tumors represent 25–30% of lung neoplasms. Surgery provides good survival for differentiated tumors (typical and atypical carcinoids), but is not useful for aggressive poorly differentiated forms. Somatostatin (SRIF) analogs can be used as medical therapy, prolonging patient survival. However, the compounds employed so far did not display antiproliferative effects. Recently, a new stable SRIF analog, pasireotide (SOM230), which activates SSTR1, ...

Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Patients present signs of hormone excess: virilisation, Cushing’s syndrome or only enlarged abdominal mass. Incidentally ACC can be also detected in the ultrasonography. Some of ‘non-hypersecretory’ ACCs can produce non-bioactive hormones steroid precursors or not very big amount of them and sometimes patients present subclinical Cushing’s symptoms. Surgery and adjuvant radiotherapy and ...

The CNC is a dominantly syndrome, characterized by spotty skin pigmentation, endocrine overactivity and myxomas (Carney & Young 1992), associated with lentigines and blue naevi; the disease links to 17q22-24, and its mutations have been identified in the genes PRKAR1α. The most common endocrine manifestations affect two o more endocrine glands, including acromegaly, thyroid and testicular tumours and ACTH-independent Cushing’s syndrome due to primary pigmented no...

Background: Acromegalia is an infrequent chronic disease requiring lifelong control. A total of about 350 Danish patients have acromegalia. It is difficult for this patient group to find information on coping strategies in fellow patients.There are numerous international quantitative studies on the symptoms in acromegalia patients; no qualitative studies on self-observations as a way to exchange experiences and optimize nursing in connection with hospita...

Standard treatment of adrenocortical carcinoma (ACC) comprises adrenolytic therapy with mitotane. Prolongation of bleeding time has previously been observed based on a series of 7 patients (Haak et al. 1991). As patients with ACC frequently undergo surgery for local recurrence or metastases, we have studied the effect of mitotane on coagulation in 44 patients with ACC before and/or during treatment with mitotane (total sample size n=62).Pla...

Background: Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism is routinely performed in many centres. Various preoperative and intraoperative localisation techniques are used along with intraoperative PTH monitoring (IOPTH).Results: We report the results of 110 consecutive patients presenting to our unit with a diagnosis of primary hyperparathyroidism from January 2004 until November 2007. All patients had sestamibi scintigraphy ...

Background: Radioiodine (131I) therapy is performed in patients with differentiated thyroid cancer (DTC), either for thyroid remnant ablation or treating distant metastasis. Although 131I therapy is generally considered safe, a genotoxic damage has been demonstrated both in vivo and in vitro.Aim: To evaluate the possible effect of Ginkgo biloba extract (EGb 761) supplementation on the time-course (up to 1...

Background: NETs are rare tumours arising from dispersed neuroendocrine system. Nevertheless, their estimated prevalence increased lately, mostly due to progress in imaging, biochemical and histopathological diagnostics.The aim of the study was to present the characteristics of the NETs patient surveyed in our Endocrinology Department since 2000.Material and methods: One hundred and fifty-eight patients (males – 42.4%, females...

Background: Acromegaly is characterized by disabling symptoms and relevant comorbidities. Insulin resistance, leading to glucose intolerance is one of the most important contributory factor to the cardiovascular mortality in acromegaly.Aim: To assess the impairments of glucose homeostasis in acromegalic patients and find association between activity of the disease and the severity of glucose intolerance.Patients and methods: In thi...

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands; MEN 2 is defined by medullary thyroid carcinoma in association with phaeochromocytoma and appears in several clinical variants, which may be inherited as autosomal dominant syndromes. Mutational analysis of RET protooncogene has been use in the diagnosis and management of patients and families with MEN 2 variants.Aim: In this study, we ...

Introduction: Transsphenoidal adenomectomy is the treatment of choice in secreting pituitary adenomas with the symptoms of Cushing’s disease, acromegaly as well as few cases of Prolactinoma, which – due to resistance to pharmacological treatment – require surgery. The efficacy of selective adenomectomy ranges from 60 to 95%. It is the highest in patients with well-visualized by MRI microadenomas, lower in macroadenomas and the lowest when the surgery was ...

Background: Neurosurgery is treatment of choice in patients with GH-secreting pituitary adenoma. However, in about 50% of cases surgery is ineffective or contraindicated. Long-acting somatostatin analogues are possible, although expensive therapeutic alternative. Generally, 60–70% of patients with active disease responds to such medical treatment.Aim: Aim of this study was to identify factors influencing medical treatment outcome and to determine if...

A 72-year-old depressed woman complained about fatigue, weight gain (20 kilos/2 years), severe and recent hypertension, easy bruises, and venous insufficiency. Whereas she was treated with six antihypertensive drugs, she had hypokaliemia (2.6 mM). Cardiac ultrasounds showed myocardial hypertrophy. A Cushing syndrome was suspected. UFC was increased (400 mM/d), cortisol cycle disrupted and a standard DXM test showed no cortisol suppression (775 nM/l). ACTH levels were consisten...

A 61-year-old man was hospitalized for paresthesias and renal insufficiency (creatinine clearance 24 ml/min) with proteinuria. Type 2 diabetes was diagnosed in 2003 and hypertension in 2007. Hypercalcemia (4.6 mM) with normal phosphorus level 1.23 mM was discovered with very high PTH levels (863 ng/l; N<78). MIBI scintigraphy localized a right inferior parathyroid tumour. No obvious sign favouring MEN1 was observed and no familial case was reported. After a short pa...

Purpose: The purpose of this study was to evaluate the histologic spectrum of stromal–epithelial patterns of invasion in ovarian serous and mucinous tumors of low malignant potential.Materials and methods: We retrospectively analyzed 31 cases of borderline ovarian serous and mucinous tumors diagnosed of the Pathology Department of County Hospital Timisoara in a period of 5 years, between 2003 and 2007. Epithelial architecture, the patterns of stroma...

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder, associated with mutations of the MEN1 gene, characterised by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary.Aim: To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1.Patients and methods: We studied 4 ...

Ghrelin is a 28-aa peptide originally isolated from stomach but present also in many tissues, including hypothalamus and pituitary, where it stimulates growth hormone (GH) release through the ghrelin/GH secretagogue receptor (GHS-R). Ghrelin also increases food intake and adiposity and could play a key integrative role in the endocrine–metabolic interface. Although its primary pituitary cell target are somatotropes, ghrelin also modulates other pituitary cell types, speci...

Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis. Accordingly, in many cases, the attending doctors have no previous experience with the disease. The aim of our study was to evaluate the quality of care in a large number of patients with ACC in Germany. Data from 263 adult patients of the German ACC registry were analyzed with regard to the following parameters: time to diagnosis, hormonal assessment, imaging, histopathological documentation, follow-up. The...

Various alterations of the cyclic AMP (cAMP) signalling cascade has been observed in adrenocortical tumors. Changes of the PKA regulatory subunits expression in tumors may positively or negatively regulate proliferation. 8CL-cAMP, a site selective cAMP analogue, induces growth inhibition in a variety of human cancer cell lines. The aim of the study was to determine if 8CL-cAMP acts on adrenocortical carcinoma H295R cell growth.We have determined the invo...

Hyperprolactinaemia is the most common disturbance in the pituitary gland function. Different physiological and patological conditions could influnce prolactin (PRL) secretion. Prolactin secreting tumors (micro and macroprolactinomas) are rare in children and adolescents (estimated incidence is 1 per milion). Functional diversity of prolactin action is responsable for different initial clinical expression of hyperprolactinaemia.We investigated causes of ...

The malignant phenotype of small cell lung cancer (SCLC) cells critically relies on the autocrine stimulation of G12/13- and Gq/11-coupled neuropeptide receptors. By this means, G12/13- and Gq/11-dependent signalling pathways are constitutively activated in these cells. While Gq/11-dependent signalling has been shown to promote proliferation of SCLC cells, the role of signalling pathways via G12/13 is still elus...

Background: Pituitary adenomas (PA) are considered very rare conditions, with an estimated prevalence of 25 cases/100 000 inhabitants. However, community-based studies on the prevalence of PA are currently scant.Aim: To ascertain the prevalence of PA and the characteristics of the patients diagnosed with them in a large population of inhabitants.Methods: A survey on the GP surgeries of Banbury (Oxfordshire, UK) covering 89 334 inha...

The incidence of GNT appears to be increasing, what can be explained by the increased detection caused by the common use of the endoscopy and the pervasive use of acid suppressive therapy leading to enterochromatofine like cells proliferation. There are numerous new diagnostic/therapeutic GNT methods in use like: EUS, SRS, somatostatin therapy and 90Y/177Lu-DOTA-TATE radiotherapy.Materials and methods: In 1998–2007, 25 patients were diagnosed with t...

Mutation Y791F of RET protooncogene is a well known mutation so far described in families with FMTC and familial pheochromocytoma in one family. It activates the receptor in a monomeric form. Here we present eight unrelated families with the same mutation but different fenotype expression.Patients and methods: In last 20 years, we analyzed 216 patients with MTC (age range: 3–75 years, 45.0 mean). Genetic testing for mutation in RET pro...

Ghrelin is a somatotrophic, orexigenic and adipogenic hormone that has an important homeostatic role by linking regulatory systems for growth and energy balance. Ghrelin- secreting neuroendocrine tumors are rare, but we had the opportunity to study a 71 years old female patient with a gastric ghrelinoma. The patient was submitted to gastroenterological examination after having episodes of diarrhea, and small subepithelial polyp (5 mm) was revealed on gastroscopy. Pathohystolog...

Full gene coding sequence of somatostatin receptor 5 and 2000 bp of upstream region was estimated using direct sequencing in 28 patients with acromegaly and 97 controls. Total 19 polymorphisms were identified (SNP1-19) and possible haplotypes were reconstructed. From all polymorphisms found silent substitution SNP15 was significantly associated with acromegaly as compared with control group (P=0.005). Another substitution SNP17 involves the amino acid change from prolin...

Introduction: Cyclic Cushing syndrome (CCS) involves rhythmic fluctuations in ACTH secretion resulting in a cyclic variation of adrenal steroid production.Case presentation: A 37-year-old woman was referred to our Pituitary Clinic in 1999, for evaluation of galactorrhea and irregular menses that had started four months ago. She also complained of depression, facial hirsutism, alopecia and progressive obesity. Blood pressure was normal. Endocrinological e...

Raloxifene (RAL) is a selective estrogen receptor (ER) modulator (SERM) proposed for chemoprevention of breast cancer and osteoporosis. SERMs exert agonist–antagonist effects depending on tissue or ERs expressed. RAL induces apoptosis in both androgen-dependent and independent cell lines, suggesting a selective activation of ERβ and prevalent antagonist effect on ERα in prostate cells (PC). In this study we evaluated effects of estradiol (E2) and RAL on epitheli...

Introduction: There are limited data on the incidence and prevalence of pituitary adenomas (PA). Although classically considered rare, systematic assessments from autopsy and radiological studies have shown a prevalence of 17% in the general population.Objective: We describe the epidemiologic of PA in Braga, the third most populous district of Portugal (860 000 inhabitants, 2673 km2), over the last 20 years.Methods: We r...

Background: Aberrant accumulation of cytoplasmic/nuclear β-catenin frequently occurs in breast cancers and breast cancer cell lines. Deregulated expression of Wnt ligands, sFRP1 and Dvl1, but no inactivating or activating mutations in Wnt signaling components have so far been reported. We have recently described an internally truncated LRP5 receptor (LRP5Δ) in 91% of hyperparathyroid tumors, and showed that LRP5Δ was strongly implicated in the aberrant accumulat...

The pocket protein family members, pRb, p107 and p130, are negative regulators of the cell cycle. But, while the role of pRB as a tumor suppressor has been extensively established, genetic inactivation of p107 or p130 is uncommon in tumors. Previous studies have shown that p130 cooperates with the CDK inhibitor p27Kip1 restricting proliferation of mouse intermediate lobe pituitary cells. Accordingly double knockout mice show higher incidence of pituitary tumors than single KO ...

Introduction: Ghrelin is known to strongly stimulate growth hormone release from the pituitary. It was also found to be produced locally in hypothalamus and anterior pituitary and in different types of pituitary adenomas. It’s been suggested that ghrelin synthesized locally in hypothalamo–pituitary area or within pituitary tumours can be an important factor contributing to pituitary tumorogenesis.Aim: The aim of the study was the immunohistoche...