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Showing papers in "Neuroendocrinology in 2006"


Journal ArticleDOI
TL;DR: The transsphenoidal route is the most widely used technique for pituitary adenoma surgery due to its rapidity, good tolerance, effectiveness and low complication rate, but tumor removal was notably superior when dealing with tumors having an extrasellar extension.
Abstract: The transsphenoidal route is the most widely used technique for pituitary adenoma surgery due to its rapidity, good tolerance, effectiveness and low complication rate. These are the parameters we utilized in comparing endoscopic with microscopic transsphenoidal surgery. We reviewed the medical records of 418 patients affected by pituitary adenomas who underwent endoscopic transsphenoidal surgery between May 1998 and December 2004, and in this paper, we present the results of 381 patients who fulfilled the follow-up criteria after a minimum period of 15 months. Our experience confirms the previous data on the rapidity and satisfactory tolerance of the endoscopic procedure. We also confirm the low complication rate, specifying that complications characteristic of the approaching phase were certainly reduced; instead, complications characteristic of tumor removal still remained similar to those reported in the microsurgical literature. The results were comparable with those of the best microsurgical series regarding endosellar lesions, but tumor removal was notably superior when dealing with tumors having an extrasellar extension. The improvement may be explained by the excellent vision of the deep surgical fields due to the endoscope and by the extreme flexibility of the surgical trajectory, mainly due to the absence of the divaricator, giving access to the ramifications of the tumor, otherwise difficult to reach.

262 citations


Journal ArticleDOI
TL;DR: a Digestive Diseases Branch, NIH, Bethesda, Md, USA; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Department of Hepatology and Gastroenterology, CHV A Pare Hospital, Boulogne , France; d Department of GastroEnterology, North Hampshire Hospital, Hampshire , UK.
Abstract: a Digestive Diseases Branch, NIH, Bethesda, Md. , USA; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Department of Hepatology and Gastroenterology, CHV A Pare Hospital, Boulogne , France; d Department of Gastroenterology, North Hampshire Hospital, Hampshire , UK; e Department of Surgery, Vivantes Humboldt Hospital, Berlin , Germany; f Department of Radiology, Royal Marsden Hospital, Sutton , UK; g Department of Pathology, Verona University, Verona , Italy; h Department of Radiology, Uppsala University, Uppsala , Sweden; i Department of Pathology, Universitatsspital Zurich, Zurich , Switzerland; j Department of Endocrinology and Metabolism, Hadassah University, Jerusalem , Israel; k Department of Oncology, Alexander Fleming Institute, Buenos Aires , Argentina; l Laboratory of Molecular Imaging and Experimental Radiotherapy, Universite Catholique de Louvain, Brussels , Belgium; m Department of Pathology, University Hospital of Kiel, Kiel , Germany

256 citations


Journal ArticleDOI
TL;DR: Departments of a Surgery and b Radiology, University of Verona, Verona , Italy; c Department of Internal Medicine, Charite, university of Berlin, Berlin , Germany; d Department of Nuclear Medicine,University of Rotterdam, Rotter Amsterdam , The Netherlands; f Department of Oncology, South Florida University, Tampa, Fla.
Abstract: Departments of a Surgery and b Radiology, University of Verona, Verona , Italy; c Department of Internal Medicine, Charite, University of Berlin, Berlin , Germany; d Department of Nuclear Medicine, University of Rotterdam, Rotterdam , The Netherlands; e M. Korner, University of Bern, Institut fur Pathologie, Bern , Switzerland; f Department of Oncology, South Florida University, Tampa, Fla. , USA; g Department of Internal Medicine, Charite, University of Berlin, Berlin , Germany; h Department of Radiology, Charite Universitatsmedizin, Berlin , Germany; i Department of Surgery, Stadtisches Klinikum Neuss, Lukas Hospital, Neuss , Germany; j Department of Surgery, Zurich Hospital, Zurich , Switzerland; k Department of Surgery, Vivantes Humboldt Hospital, Berlin , Germany; l Department of Endocrine Oncology, University of Uppsala, Uppsala , Sweden; m Department of Pathology, University of Lyon, Lyon , France

244 citations


Journal ArticleDOI
TL;DR: a Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam, The Netherlands; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria;
Abstract: a Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam, The Netherlands; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Hospices Civils de Lyon, Hopital Edouard-Herriot Service Central d‘Anatomie et Cytologie Pathologiques, Lyon , France; d Centre de Medecine Nucleaire, Universite Catholique de Louvain, Brussels , Belgium; e Department of Pathology, University of Kiel, Kiel , Germany; f B Unit of Surgery, Department of Surgery, University of Verona, Verona , Italy; g Department of Nuclear Medicine, Erasmus MC, Rotterdam , The Netherlands; h Department of Endocrine Oncology, University Hospital, Uppsala , Sweden; i Department of Internal Medicine, Division of Hepatology and Gastroenterology, Interdisciplinary Center of Metabolism and Endocrinology, Charite, Campus Virchow Hospital, University for Medicine Berlin, Berlin , Germany; j Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l‘Appareil Digestif, Hopital Beaujon, Clichy , France; k Department of Pathology and Laboratory Medicine, Universita degli Studi, Parma, Italy; l Department of Endocrinology, Genoa University, Genoa , Italy

232 citations


Journal ArticleDOI
TL;DR: A very complex system of six IGF binding proteins provides a sophisticated system for conferring specificity to provide a finely tuned system for local regulation at the tissue level.
Abstract: Insulin-like growth factors (IGFs) are fundamental cell regulators with an evolutionary conserved role synchronising tissue growth, development and function according to metabolic conditions. Although structurally very similar to insulin, the IGFs act in a very different way as cell regulators. Whereas insulin is stored in a specific gland and released when needed, the IGFs are stored outside of cells with soluble binding proteins. A very complex system of six IGF binding proteins, each of which exists in various modified states and interacts with other proteins, provides a sophisticated system for conferring specificity to provide a finely tuned system for local regulation at the tissue level.

154 citations


Journal ArticleDOI
TL;DR: a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Digestive and Liver Disease, Ospedale S. Andrea, Rome , Italy; c Department of Hepatology and GastroEnterology, CHU Bichat – B. Mourier Hospital, Colombes, France; d Department of Pathology, Kantonsspital Baden , Switzerland.
Abstract: a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Digestive and Liver Disease, Ospedale S. Andrea, Rome , Italy; c Department of Hepatology and Gastroenterology, CHU Bichat – B. Claude Bernard University, Paris , France; d Department of Pathology, Kantonsspital Baden , Switzerland; e Department of Gastroenterology, Massachussetts General Hospital, Boston , Mass. , USA; f B. Kos-Kudla, Department of Endocrinology, Slaska University, Zabrze , Poland; g Department of Surgery, UFR Bichat-Beaujon-Louis Mourier Hospital, Colombes , France; h Department of Oncology, Royal Free University, London , UK; i Department of Gastroenterology, Philipps University, Marburg , Germany; j Department of Surgery, Gothenburg University, Gothenburg , Sweden; k Department of Nuclear Medicine, Catholique de Louvain University, Brussels , Belgium; l Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; m Department of Pathology and Laboratory Medicine, Universita degli Studi, Parma , Italy

134 citations


Journal ArticleDOI
TL;DR: Data provide strong evidence for a central role of kisspeptins and GPR54 as molecular conduits for the metabolic regulation of reproductive function – a phenomenon with potential physiopathologic and therapeutic implications.
Abstract: Unraveling of the master role of kisspeptins, the products of the KiSS-1 gene, and their receptor, GPR54, in the control of reproduction has been a major breakthrough in contemporary neuroendocrinology. Indeed, since the disclosure of their reproductive dimension in late 2003, an ever-growing number of genetic, molecular, physiologic and pharmacological studies have defined the crucial role of KiSS-1 neurons as central processors for the dynamic regulation of the gonadotropic axis and its full activation at puberty. Yet, the potential role of the hypothalamic KiSS-1 system as an intermediary factor for the well-known interplay between energy status and reproduction initially received little attention. Recent data, however, strongly suggest a prominent role of KiSS-1 in the metabolic control of fertility, as expression of KiSS-1 gene at the hypothalamus is down-regulated in conditions of negative energy balance and kisspeptin administration is capable of overcoming the hypogonadotropic state observed in undernutrition and disturbed metabolic conditions. Leptin, the adipocyte hormone signaling the size of body energy stores, is likely to play a pivotal role in the metabolic control of the KiSS-1 system, since kisspeptin neurons express leptin receptors and leptin is able to normalize defective KiSS-1 gene expression in models of impaired gonadotropin secretion linked to hypoleptinemia, such as the ob/ob mouse and streptozotocin-induced diabetic rat. In sum, these data provide strong evidence for a central role of kisspeptins and GPR54 as molecular conduits for the metabolic regulation of reproductive function - a phenomenon with potential physiopathologic and therapeutic implications.

125 citations


Journal ArticleDOI
TL;DR: a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Oncology, Institut Catala d’Oncologia, Barcelona , Spain; c Department of Surgery, Verona University, Ver Italy; d Department of Endocrinology and Metabolism, Genimatas Hospital, Athens , Greece.
Abstract: a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Oncology, Institut Catala d’Oncologia, Barcelona , Spain; c Department of Surgery, Verona University, Verona , Italy; d Department of Endocrinology and Metabolism, Genimatas Hospital, Athens , Greece; e Department of Gastroenterology, Beaujon Hospital, Clichy , France; f Department of Endocrinology, Erasmus MC University, Rotterdam , The Netherlands; g Department of Internal Medicine, Martin University, Martin , Slovakia; h Department of Propaedeutic Internal Medicine, Laiko Hospital, Athens , Greece; i Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; j Department of Gastroenterology, Beaujon Hospital, Clichy , France; k Department of Gastroenterology, Royal Free Hospital, London , UK; l Department of Cell Biology, National Institute of Health, Bethesda, Md. , USA; m Department of Endocrinology, University Hospital, Uppsala , Sweden

122 citations


Journal ArticleDOI
TL;DR: A department of Pathology, gothenburg University, Gothenburg , Sweden, and a Department of Gastroenterology, Gasthuisberg University, Leuven, Belgium are listed.
Abstract: a Department of Pathology, Gothenburg University, Gothenburg , Sweden; b Department of Gastroenterology, Gasthuisberg University, Leuven , Belgium; c Department of Gastroenterology, Ospedale S. Andrea, Rome , Italy; d Department of Oncology, University of Texas, Houston, Tex. , USA; e Department of Endocrinology, Erlangen University, Erlangen , Germany; f Department of Oncology and Pathology, Royal Infirmary Hospital, Glasgow , UK; g Department of Oncology, Virgen de la Victoria Hospital, Malaga , Spain; h Department of Nuclear Medicine, Medizinische Hochschule Hannover, Hannover , Germany; i Department of Endocrinology, Erciyes University, Kayseri , Turkey; j Department of Surgery, Beaujon Hospital, Clichy , France; k Department of Nuclear Medicine, Catholique de Louvain University, Brussels , Belgium; l Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; m Department of Gastroenterology, Royal Free Hospital, London , UK

114 citations


Journal ArticleDOI
TL;DR: Preoperative treatment with somatostatin analogues reduces the comorbidity and facilitates adenoma removal which is still controversially discussed in the literature and the complication rate of microsurgery in experienced hands is low.
Abstract: The aim of this short review is to inform about the possibilities and limits of transnasal microsurgery in acromegaly. The current reports on surgical remissions, according to the strict criteria with international consensus using age- and sex-related normal levels for insulin-like growth factor-I and suppression of growth hormone (GH) with oral glucose tolerance below 1 mug/l, are more or less agreeable with values between 34 and 74%. In microadenomas (<10 mm in diameter), 59-95% remissions are published. Some improvement might be achieved in macroadenomas which presently have a chance of 26-68% to be satisfactorily operated on. Special instruments introduced by us to visualize and remove partially invasive adenoma parts are described. Intraoperative magnetic resonance imaging is discussed. With intraoperative measurement of GH, small adenoma rests <3 mm can be diagnosed. When GH did not sufficiently decline, an additional tumor search resulted in a significant improvement in results in resectable macroadenomas. With these techniques, we achieved remission rates which can hardly be further increased (micros 95%, macros 68%). In grossly invasive grade 4 adenomas, which are frequent in our unit, only an 80-95% reduction in tumor mass is feasible. Preoperative treatment with somatostatin analogues as used in most of our patients reduces the comorbidity and facilitates adenoma removal which is still controversially discussed in the literature. The complication rate of microsurgery in experienced hands is low.

113 citations


Journal ArticleDOI
TL;DR: Quality of life (QoL) is impaired in acromegaly, especially in active disease, and QoL is associated with the presence of musculoskeletal pain, headache, having required treatment with radiotherapy, being older, of female gender, with a longer disease duration, coexisting diabetes mellitus, a higher BMI or becoming GH deficient after treatment for acromEGaly.
Abstract: Available disease-specific questionnaires like the Acromegaly Quality of Life questionnaire have confirmed that quality of life (QoL) is impaired in acromegaly, especially in active disease. Successful therapy improves QoL, but it may not normalize completely even after endocrine cure; furthermore, there is not always a correlation between growth hormone (GH) and insulin-like growth factor 1 and subjective health perception of QoL. Appearance is the dimension most affected and has the highest impact on the patient's QoL. Worse QoL is associated with the presence of musculoskeletal pain, headache (if only medical therapy, not surgery, has been provided), having required treatment with radiotherapy, being older, of female gender, with a longer disease duration, coexisting diabetes mellitus, a higher BMI or becoming GH deficient after treatment for acromegaly.

Journal ArticleDOI
TL;DR: It is demonstrated that estrogens were locally synthesized in the adult hippocampal neurons and that synaptic ERα can drive rapid modulation of synaptic plasticity by endogenous estradiol.
Abstract: In neuroendocrinology, it is believed that steroid hormones are synthesized in the gonads and/or adrenal glands, and reach the brain via the blood circulation. In contrast to this view, we are in prog

Journal ArticleDOI
TL;DR: CNC is the first human disease caused by mutations of one of the subunits of the PKA holoenzyme, a critical component of numerous cellular signaling systems, and has wide implications for cAMP involvement in endocrine tumorigenesis.
Abstract: Carney complex (CNC) is a unique multiple endocrine neoplasia syndrome (MIM 160980) which is characterized by unusual biochemical features (chronic hypersomatotropinemia and paradoxical responses of c

Journal ArticleDOI
TL;DR: It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex.
Abstract: Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 +/- 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

Journal ArticleDOI
TL;DR: These findings suggest that the neuroprotective actions of estradiol and IGF-I after brain injury depend on the coactivation of both ERs andIGF-IR in neural cells.
Abstract: The actions of estradiol in the brain involve the interaction with growth factors, such as insulin-like growth factor-I (IGF-I). Many cells in the brain coexpress receptors for estradiol (ERs) and IGF-I (IGF-IR) and both factors interact to regulate neural function. Several studies have shown that there is an interaction of IGF-IR and ERs in neuroprotection. Neuroprotective effects of estradiol are blocked by the inhibition of IGF-IR signaling, while the neuroprotective effects of IGF-I are blocked by the inhibition of ER signaling. These findings suggest that the neuroprotective actions of estradiol and IGF-I after brain injury depend on the coactivation of both ERs and IGF-IR in neural cells. The relationship of ERalpha with IGF-IR through the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta (PI3K/Akt/GSK3) signaling pathway may represent the point of convergence used by estradiol and IGF-I to cooperatively promote neuroprotection. Administration of estradiol to ovariectomized rats results in the association of ERalpha with IGF-IR and with components of the PI3K/Akt/GSK3 signaling pathway and in the regulation of the activity of Akt and GSK3 in the brain. Conversely, IGF-I regulates ERalpha transcriptional activity in neuroblastoma cells and the PI3K/Akt/GSK3 signaling pathway is involved in this effect.

Journal ArticleDOI
TL;DR: In this paper, the authors used DNA labeling techniques to identify apoptotic cells and found that a higher apoptotic LI was found in functioning compared with nonfunctioning adenomas, in microadenomas, particularly in corticotrope adnomas, and in untreated adenoma, particularly prolactinomas.
Abstract: The optimal goal for pathologists is to provide important information to clinicians in order to predict tumor biology. Specific morphologic features may serve as predictive markers of tumor behavior. Macroscopic invasion of the perisellar tissues, defined as radiographic or gross operative finding, is considered a more consistent prognostic indicator. Regarding morphology, cytologic atypia is not a reliable feature. In contrast, the number of mitoses is very important for prognosis. Given that only scarce mitoses can be identified in some aggressive cases, Ki-67 represents an alternative key feature to assess tumor proliferation. In the recent World Health Organization classification, the Ki-67 labeling index (LI) represents a major prognostic indicator for pituitary adenomas. Expression of the p53 gene product is very important for tumor biology. Adenomas with more than 3% Ki-67 LI and extensive p53 immunoreactivity are classified as 'atypical adenomas'. Apoptosis and mitoses represent two adverse and asynchronous events, maintaining the optimal cell numbers. Using DNA labeling techniques, we can identify apoptotic cells. A higher apoptotic LI was found in functioning compared with nonfunctioning adenomas, in microadenomas, particularly in corticotrope adenomas, and in untreated adenomas, particularly prolactinomas. Cytogenetic analysis of chromosomes may provide important information regarding tumor development and progression. Increased chromosome 11 copies are more frequent in functioning, aneuploid pituitary adenomas. Monosomy or partial loss of chromosome 11 in adenomas with a normal or increased DNA LI indicates complex genomic abnormalities of chromosomes, other than chromosome 11. Immunohistochemical detection of somatostatin receptors is important, as their density in the cytoplasmic membrane is directly related to the effectiveness of somatostatin analogues. Therefore, morphologic assessment of the somatostatin receptor profile can predict the responsiveness and validate the effectiveness of treatment with somatostatin analogues. We can conclude that among the currently available predictive factors, tumor invasiveness is important, whereas the presence of mitoses, the Ki-67 LI, p53 expression and apoptosis are very important; DNA ploidy and fluorescent in situ hybridization analysis, although important, are difficult to apply. Finally, in the near future, immunohistochemistry for somatostatin receptors will be a very important application.

Journal ArticleDOI
TL;DR: Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction, and an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory.
Abstract: Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully treated, concentric biventricular hypertrophy and diastolic dysfunction can develop and, at least, lead to diastolic congestive heart failure. Rhythm disturbances and valve dysfunction are also frequently described in acromegaly. The coexistence of other complications, such as diabetes and arterial hypertension, can induce the worsening of acromegalic cardiomyopathy. Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction. In conclusion, an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory in acromegaly.

Journal ArticleDOI
TL;DR: A large number of the subjects studied had previously been diagnosed with central giant cell granuloma, a leading cause of Digestive Diseases encephalopathy, and the use of these lesions in humans is still a new phenomenon.
Abstract: a Digestive Diseases Branch, NIDDK, NIH, Bethesda, Md. , USA; b Dipartimento di Patologia e Medicina di Laboratorio, Universita di Parma, Parma , Italy; c Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps University, Marburg , Germany; d Department of Pathology, IPATIMUP Hospital, Porto , Portugal; e Dipartimento di Fisiopatologia Clinica, Universita di Firenze, Firenze , Italy; f Department of Surgery, Johann-Wolfgang-Goethe-Universitat, Frankfurt , Germany; g E. Christ, Department of Endocrinology, Inselspital, Bern , Switzerland; h Department of Oncology, Netherlands Cancer Centre, Amsterdam , The Netherlands; i Department of Surgery, Rigshospitalet Blegdamsvej Hospital, Copenhagen , Denmark; j Department of Surgery, Gothenburg University, Gothenburg , Sweden; k Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam , The Netherlands; l Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l’Appareil Digestif, Hopital Beaujon, Clichy , France

Journal ArticleDOI
TL;DR: The variable patterns of response to sst2, sst5 and dopamine D2 analogs may explain the greater efficacy of drugs which bind to the 3 receptors in suppressing GH secretion.
Abstract: Aim: We report the comparative efficacy of octreotide, cabergoline and multiple ligands directed towards the different somatostatin subtypes (ssts), such as BIM-23A779 and SOM-230,

Journal ArticleDOI
TL;DR: Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery.
Abstract: Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.

Journal ArticleDOI
TL;DR: There is some evidence to suggest that breast and prostatic malignancies might also be increased in acromegaly, however, these associations have been based mostly on small epidemiological surveys and circumstantial evidence.
Abstract: Acromegaly is characterised by excessive levels of circulating growth hormone and its tissue mediator, insulin-like growth factor (IGF)-I Prior to effective treatment and lowering of growth hormone and IGF-I, the majority of patients with the disease died by the age of 60 years, largely due to diabetes mellitus, cardiovascular and cerebrovascular diseases More recently, it has become apparent that patients with acromegaly may also have an increased prevalence of colorectal adenomas and cancer This may be due to elevated IGF-I, which is implicated in the development of sporadic colorectal cancer, and environmental factors, such as the bile acid deoxycholic acid, the levels of which are also increased in acromegaly There is some evidence to suggest that breast and prostatic malignancies might also be increased in acromegaly However, these associations have been based mostly on small epidemiological surveys and circumstantial evidence Large-scale epidemiological studies are required to clarify this issue

Journal ArticleDOI
TL;DR: Analysis of data from 110 consecutive patients operated on transsphenoidally for pituitary and hypothalamic tumors showed that postoperative hyponatremia after TSS was not rare, and the hypon atremia was mainly associated with SIADH.
Abstract: Transient diabetes insipidus is a well-known complication after transsphenoidal surgery (TSS). On the other hand, transient hyponatremia has been reported as being a delayed complication of TSS. Trans

Journal ArticleDOI
TL;DR: Combined treatment of a somatostatin analog with pegvisomant appears to be an effective and rational approach.
Abstract: The currently available long-acting somatostatin analogs normalize serum growth hormone (GH) levels and insulin-like growth factor-I levels in approximately 60% of patients with acromegaly. The recently introduced GH receptor antagonist, pegvisomant, is able to normalize insulin-like growth factor-I levels in virtually all acromegalic subjects. Although no correlation between increased GH concentrations and tumor size has been found, long-term safety studies are still in progress. Also, pegvisomant monotherapy is administered once daily and is very costly. Combined treatment of a somatostatin analog with pegvisomant appears to be an effective and rational approach.

Journal ArticleDOI
TL;DR: The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson’s staining techniques, identified ‘helle Zellen’ within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system.
Abstract: As early as the 2nd century, Galen proposed that 'vital spirits' in the blood regulated human bodily functions. However, the concept of hormonal activity required a further 18 centuries to develop and relied upon the identification of 'ductless glands', Schwann's cell and the recognition by Bayliss and Starling of chemical messengers. Bernard's introduction of 'internal secretion' and its role in homeostasis laid a physiological basis for the development of endocrinology. Kocher and Addison recognized the consequences of ablation of glands by disease or surgery and identified their necessary role in life. Detailed descriptions of the endocrine cells of the gut and pancreas and their putative function were provided by Heidenhain, Langerhans, Laguesse and Sharpey-Schafer. Despite the dominant 19th century concept of nervism (Pavlov), in 1902, Starling and Bayliss using Hardy's term 'hormonos' described secretin and in so doing, established the gut as an endocrine organ. Thus, nervism was supplanted by hormonal regulation of function and thereafter numerous bioactive gut peptides and amines were identified. At virtually the same time (1892), Ramon y Cajal of Madrid reported the existence of a group of specialized intestinal cells that he referred to as 'interstitial cells'. Cajal postulated that they might function as an interface between the neural system and the smooth muscles of the gut. Some 22 years later, Keith suggested that their function might be analogous to the electroconductive system of the heart and proposed their role as components of an intestinal pacemaker system. This prescient hypothesis was subsequently confirmed in 1982 by Thuneberg and a decade later Maede identified c-Kit as a critical molecular regulator in the development and function of the interstitial cells of Cajal and further confirmed the commonality of neural and endocrine cells. The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson's staining techniques, identified 'helle Zellen' within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system. Pearse subsequently grouped the various cells belonging to that system under the rubric of a unifying APUD series. Currently, the gut neuroendocrine system is viewed as a syncytium of neural and endocrine cells sharing a common cell lineage whose phenotypic regulation is as yet unclear. Their key role in the regulation of gastrointestinal function is, however, indubitable.

Journal ArticleDOI
TL;DR: The histologic, immunohistochemical and electron microscopic study provided conclusive evidence that a marked diversity exists between the tumors which secrete growth hormone in excess, such as densely and sparsely granulated GH cell adenoma, the mixed GH prolactin cellAdenoma and the mammosomatotrope adenomas.
Abstract: This review summarizes current knowledge on pituitary changes in patients with acromegaly. The histologic, immunohistochemical and electron microscopic study provided conclusive evidence that a marked

Journal ArticleDOI
TL;DR: The Conference was divided sequentially into 8 sessions devoted to specific topics on an anatomical basis, using as a basis the published text of the ENETS Guidelines so that specific questions could be prepared and presented to different working groups.
Abstract: Sixty-two experts active in the field of digestive NETs from 20 different countries attended the first Consensus Conference. Attendees were invited on the basis of their proven expert scientific and clinical experience in NETs. The attendees represented all medical disciplines involved in managing patients with digestive NETs. They were assigned to four working groups according to their specific clinical expertise: (1) Pathology and Genetics (11 participants); (2) Surgery (10 participants); (3) Imaging and Radiology (10 participants), and (4) Medicine and Clinical Pathology (31 participants). The complete list of delegates is provided at the end of this commentary, as well as at the end of each of the six following papers. The Conference was divided sequentially into 8 sessions devoted to specific topics on an anatomical basis (Gastric NET, Sessions 1 and 2; Duodenal NET; Pancreatic NET, Sessions 1–4; Poorly Differentiated Endocrine Carcinomas of foregut origin). A working booklet was prepared in advance by the organizing committee, using as a basis the published text of the ENETS Guidelines so that specific questions could be prepared and presented to different working groups. The booklet was provided to the participants only at the conference venue. The Starting Point

Journal ArticleDOI
TL;DR: It is demonstrated that progesterone and MPA have a similar but not identical effect on central and peripheral allopregnanolone and β-END levels and their association with an estrogenic compound does not interfere with the positive effects produced by estrogen.
Abstract: The increased use of hormonal therapies has led to the study of the properties of different progestin molecules and their effects on the central nervous system. The central and peripheral levels of ne

Journal ArticleDOI
TL;DR: Results show that orexin A is capable of directly stimulating GnRH transcription and neuropeptide release from these immortalized hypothalamic neurons, and that the effects of orex in A appear to be mediated via the OX1R, coupled with activation of the PKC-, MAPK- and PKA-signaling pathways.
Abstract: Orexin A, a recently discovered hypothalamic peptide, has been shown to have a stimulatory effect on release of gonadotropin-releasing hormone (GnRH) from rat hypothalamic explants in vitro. However,

Journal ArticleDOI
TL;DR: The studies suggest that GLT-1b expression is regulated by stress levels of glucocorticoids (GCs) and GLt-1 expression isregulated by stress-induced increases in extracellular glutamate levels in the CA3 region.
Abstract: Background: In the rat hippocampus, the predominate glutamate transporters are GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress increases GLT-1b expression throughout the hippocampus while more selectively increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1 expression is regulated by stress-induced increases in extracellular glutamate levels in the CA3 region. Methods: In order to differentiate between the actions of GCs and glutamate, we examined GLT-1 isoform expression in adrenalectomized (ADX) rats and rats exposed to stress levels of GCs. Results: ADX rats revealed no significant differences in GLT-1b mRNA or protein levels compared to sham-operated controls or ADX rats given GC replacement. However, rats exposed to stress levels of GCs exhibited increases in GLT-1b protein expression in the CA3 region and the dentate gyrus. GLT-1 mRNA expression was increased by ADX, increases that were inhibited by GC replacement. Similarly, stress levels of GCs increased GLT-1 protein expression throughout the hippocampus. Conclusions: Taken together, these data indicate that GLT-1b protein expression is regulated by stress levels of GCs while the regulation of GLT-1 mRNA and protein expression provides another example of the biphasic actions of GCs in the central nervous system.

Journal ArticleDOI
TL;DR: It is suggested that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response.
Abstract: Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3α-reduced pregnane steroids are potent positive allosteric modulators of the γ-aminobutyric acid