Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma.

Objective Insulinomas are rare pancreatic endocrine tumors characterized by hypoglycemia. Guidelines by the Endocrine Society (ES), the European (ENETS) and the North American (NANETS) Neuroendocrine Tumor Societies provide divergent diagnostic criteria. This study compared the diagnostic accuracy of these different criteria during the 72-h fasting test.

Endothelial cells regulate β-catenin activity in adrenocortical cells via secretion of basic fibroblast growth factor.

Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCIH295R cells.

Enhanced iodine supplementation alters the immune process in a transgenic mouse model for autoimmune thyroiditis.

Background: The impact of excessive iodine intake on the development of autoimmune thyroiditis (AIT) is still under debate. Transgenic, antibody-devoid TAZ10 mice spontaneously develop AIT due to autoreactive thyroperoxidase-specific T cells. In this model, development of AIT is determined by a T cell infiltration of the thyroid gland leading to an elevation of serum thyrotropin (TSH) levels and significant weight gain.

Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line.

Hedgehog (Hh)-signaling pathway is important in embryonic development. Activation of Hh-signaling is associated with tumorigenesis. Recent studies demonstrate that Hh-signaling is involved in the development of the adrenal gland in mice and is important in regulating adrenal proliferation.

Localization and regulation of pancreatic selenoprotein P.

Progressive loss of pancreatic β-cell mass is a crucial feature of type 2 diabetes mellitus. As β-cells express very low amounts of the antioxidant enzymes catalase and glutathione peroxidase (GPx), they appear to be particularly vulnerable to oxidative damage in the pathogenesis of diabetes. Here, we investigated the pancreatic expression pattern and regulation of selenoprotein P (Sepp1), which may serve as an additional antioxidant enzyme inside and outside of cells.

Immunoregulatory natural killer cells suppress autoimmunity by down-regulating antigen-specific CD8+ T cells in mice.

Natural killer (NK) cells belong to the innate immune system. Besides their role in antitumor immunity, NK cells also regulate the activity of other cells of the immune system, including dendritic cells, macrophages, and T cells, and may, therefore, be involved in autoimmune processes. The aim of the present study was to clarify the role of NK cells within this context.

Endothelin-1 and adrenomedullin plasma levels after exposure to fludrocortisone, dexamethasone, and spironolactone.

We asked whether plasma concentrations of endothelin-1 (ET-1) or adrenomedullin (ADM) are altered by different activity states of the renin-angiotensin-aldosterone system (RAAS). Levels of ET-1 and ADM were studied in patients with primary aldosteronism (n = 15), essential hypertension (n = 15), and adrenal insufficiency (n = 7). Effects of fludrocortisone, dexamethasone, or spironolactone treatment on ET-1 and ADM levels were also analyzed.

Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto's thyroiditis.

Context: Hashimoto's thyroiditis (HT) is a common autoimmune disease leading to thyroid destruction due to lymphocytic infiltration. Only rare data are available regarding the recognition of specific cellular antigens, e.g.

Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation.

Several studies have reported a positive relationship of the body fat mass and bone density. However, it is not clear whether adipocyte-derived signaling molecules directly act on osteoblasts or osteoclasts. Therefore, we investigated the effect of fat cell-secreted factors on the proliferation and differentiation of preosteoblasts and the molecular mechanisms involved.

Exendin-4 upregulates the expression of Wnt-4, a novel regulator of pancreatic β-cell proliferation.

The Wnt-signaling pathway regulates β-cell functions. It is not known how the expression of endogenous Wnt-signaling molecules is regulated in β-cells. Therefore, we investigated the effect of antidiabetic drugs and glucose on the expression of Wnt-signaling molecules in β-cells.

A progressive increase in cardiovascular risk assessed by coronary angiography in non-diabetic patients at sub-diabetic glucose levels.

Objective: Diabetes mellitus type 2 (DM2) is a risk factor for coronary heart disease (CHD). While there is a clear correlation of fasting blood glucose (FBG) and 2 h post-challenge blood glucose values (2h-BG) with microvascular complications, the risk for CHD conferred by glucose dysregulation antecedent to DM2 is less clear. Therefore, we investigated associations of FBG and 2h-BG values with the prevalence of CHD assessed by coronary angiography as the most sensitive diagnostic tool.

Cushing's disease in a patient with steroid 21-hydroxylase deficiency.

Cushing's disease rarely appears as a consequence of hereditary disease. However, familial diseases with diminished glucocorticoid feedback are associated with secondary hypercorticotropinism and have been shown to give rise to pituitary adenomas. We here describe the rare case of a 30-year old female patient with congenital adrenal hyperplasia who also showed clinical signs and a typical history of hypercortisolism that was specified as Cushing's disease.

Increased numbers of tumor-lysing monocytes in cancer patients.

Lymphatic infiltration is a well known phenomenon in different tumors including endocrine malignancies. However, little is known about the role of antigen-presenting cells and T cell activation in this context. The aim of our study was to investigate the quantity and function of CD14+/CD56+ monocytes in tumor patients including endocrine malignancies.

Indicators of mineralocorticoid excess in the evaluation of primary aldosteronism.

It is suggested to use the aldosterone-to-renin ratio (ARR) as a first test in the screening for primary aldosteronism (PA). However, many groups rather rely on the determination of urinary tetrahydroaldosterone secretion; others calculate a ratio of urinary aldosterone to plasma renin activity. The aim of the present study was to evaluate the usefulness of different parameters of aldosterone excess in the case finding of PA.

Association of serum levels of retinol-binding protein 4 with male sex but not with insulin resistance in obese patients.

Background: Retinol-binding protein 4 (RBP4) is secreted by adipocytes and by the liver and modulates insulin sensitivity in animal models. However, controversial data exist regarding the association of serum levels of RBP4 with insulin resistance in humans. Obesity confers a major risk to develop insulin resistance.

Sporadic solitary aldosterone- and cortisol-co-secreting adenomas: endocrine, histological and genetic findings in a subtype of primary aldosteronism.

Adrenal adenomas producing both aldosterone and cortisol (A/CPAs) have been described in only a few cases. Correct subtype classification is necessary for making therapeutic decisions in primary aldosteronism (PA). Therefore, we studied in detail the clinical, hormonal and histological features of this entity in two patients with A/CPAs.

Evidence for the involvement of endothelial cell products in adrenal CITED2 expression.

The adrenal gland contains a well-organized network of blood vessels, and adrenocortical cells are situated in close proximity to endothelial cells. Recently, several new mechanisms have been characterized that control the release of aldosterone by adrenocortical cells, including the involvement of endothelial-cell-derived factors. Interestingly, a CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), which is necessary for adrenal development, has been linked to aldosterone synthesis.

Pathophysiological aspects of Wnt-signaling in endocrine disease.

Wnt-signaling has recently been identified as a regulator of a number of endocrine functions in health and disease in addition to its original attribution to developmental biology. Wnts are extracellular ligands on frizzled receptors and on lipoprotein receptor-related protein co-receptors. Ligand binding leads eventually to the activation of intracellular signaling cascades; based on the involvement of the transcriptional co-activator beta-catenin it can be distinguished between canonical (i.

Dendritic cell vaccination with xenogenic polypeptide hormone induces tumor rejection in neuroendocrine cancer.

Purpose: No relevant breakthrough has yet been achieved in the identification of tumor antigens in many neuroendocrine cancer types that exist, such as malignant gastrinoma, insulinoma, or medullary thyroid carcinoma. The aim of this study was to proof the concept of dendritic cell immunization with a tumor cell-specific polypeptide hormone as a target molecule in a transgenic mouse model for medullary thyroid carcinoma (Ret/Cal mice).

Experimental Design: Ret/Cal mice were repeatedly immunized for up to 6 months with amino acid-modified (xenogenic) calcitonin-pulsed dendritic cells.

IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo.

The antitumor effect of IFN-alpha is mediated by the activation of CTLs, NK cells, and the generation of highly potent Ag-presenting dendritic cells (IFN-DCs). In this study, we show that IFN-DCs generated in vitro from monocytes express CD56 on their surface, a marker which has been thought to be specific for NK cells. FACS analyses of CD56(+) and CD56(-) IFN-DCs showed a nearly identical pattern for most of the classical DC markers.

Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.

Context: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.