Znaczenie przedoperacyjnego zastosowania analogów somatostatyny w akromegalii

Different types of treatment, including surgery, medical therapy and radiotherapy, are possible in achieving control of acromegaly. Of the medical therapies available, somatostatin analogues are effective in the majority of patients and can induce pituitary tumour shrinkage. The rationale and outcome of somatostatin analogue treatment before surgery in patients with acromegaly is briefly presented. In summary, the benefits of somatostatin analogues given preoperatively should be considered carefully as optimisation of cardiovascular, respiratory and metabolic functions is clinically relevant for perioperative morbidity. Somatostatin analogues also induce significant shrinkage of GH-secreting pituitary tumours, although this does not seem to be helpful in terms of improved surgical outcome. (Pol J Endocrinol 2007; 58 (4): 356-360)W leczeniu akromegalii możliwe jest zastosowanie różnych form terapii (leczenie operacyjne, farmakoterapia, radioterapia). Analogi somatostatyny wykazują skuteczność u większości pacjentów i mogą powodować zmniejszenie wielkości gruczolaka przysadki. Krótki przegląd przedstawia uzasadnienie i wyniki stosowania analogów somatostatyny przed leczeniem chirurgicznym. W podsumowaniu, korzyści przedoperacyjnego zastosowania analogów somatostatyny powinny być starannie rozważone celem optymalizacji zaburzeń kardiologicznych, oddechowych i metabolicznych ważnych dla chorobowości okołooperacyjnej. Analogi somatostatyny powodują również istotne zmniejszenie guzów przysadki wydzielających GH, chociaż nie udowodniono jego wpływu na poprawę wyników leczenia neurochirurgicznego

Role of the lipid rafts in the life cycle of canine coronavirus

Coronaviruses are enveloped RNA viruses that have evolved complex relationships with their host cells, and modulate their lipid composition, lipid synthesis and signalling. Lipid rafts, enriched in sphingolipids, cholesterol and associated proteins, are special plasma membrane microdomains involved in several processes in viral infections. The extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to lipid rafts. Because cholesterol-rich microdomains appear to be a general feature of the entry mechanism of non-eneveloped viruses and of several coronaviruses, the purpose of this study was to analyse the contribution of lipids to the infectivity of canine coronavirus (CCoV). The CCoV life cycle is closely connected to plasma membrane cholesterol, from cell entry to viral particle production. The methyl-β-cyclodextrin (MβCD) was employed to remove cholesterol and to disrupt the lipid rafts. Cholesterol depletion from the cell membrane resulted in a dose-dependent reduction, but not abolishment, of virus infectivity, and at a concentration of 15 mM, the reduction in the infection rate was about 68 %. MβCD treatment was used to verify if cholesterol in the envelope was required for CCoV infection. This resulted in a dose-dependent inhibitory effect, and at a concentration of 9 mM MβCD, infectivity was reduced by about 73 %. Since viral entry would constitute a target for antiviral strategies, inhibitory molecules interacting with viral and/or cell membranes, or interfering with lipid metabolism, may have strong antiviral potential. It will be interesting in the future to analyse the membrane microdomains in the CCoV envelope

Managing Cushing's disease: the state of the art.

Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management

Nutritional and Environmental Factors in Thyroid Carcinogenesis

Several epidemiological studies suggest an increased incidence of thyroid carcinoma (TC) in recent years, especially for the papillary histotype (PTC), suggesting that specific carcinogens might promote molecular abnormalities that are typical of PTC. The increased incidence is probably attributed to more intensive and sensitive diagnostic procedures, even if recent data suggest that various toxic elements could explain the phenomenon. Ionizing radiation exposure represents the most accepted risk factor for differentiated thyroid cancer that includes both the follicular and papillary histotypes. In this review, we examined the other environmental carcinogens that play a role in TC, such as eating habits, living in volcanic areas, and xenobiotic elements. Among eating habits, iodine intake represents one of the more discussed elements, because its deficiency is associated with follicular thyroid carcinomas (FTCs), while its progressive increment seems to be responsible for PTC. The gas, ash, and lava emissions of volcanoes are composed of various toxic compounds that pollute ground water, vegetables, and animals, contaminating humans via the food chain. Finally, the risk of developing PTC has also been associated with exposure of the population to xenobiotics in the environment or in the home. Their carcinogenic effects are probably caused by their accumulation, but additional studies are necessary to better understand the mechanisms of action

Diagnosis and Differential Diagnosis of Medullary Thyroid Cancer

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Application of molecular biology of differentiated thyroid cancer for clinical prognostication

Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF(V600E) is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF(V600E) and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated

Hereditary Neuroendocrine Tumor Syndromes

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THE COMPLEX RELATIONSHIP BETWEEN OBESITY AND THE SOMATROPIC AXIS: THE LONG AND WINDING ROAD.

Despite the considerable body of evidence pointing to a possible relationship between state of the adipose tissue depots and regulation of the somatotropic axis, to date the relationship between obesity and low growth hormone (GH) status remains incompletely understood. The low GH status in obesity is mainly considered as a functional condition, largely reversible after a sustained weight loss. Moreover, due to the effects of the adiposity on the regulation of the somatotropic axis, the application of GH stimulation tests in obesity may also lead to an incorrect diagnosis of GH deficieny (GHD). On the other hand, similar to patients with GHD unrelated to obesity, the reduced GH response to stimulation testing in obese individuals is associated with increased prevalence of cardiovascular risk factors and detrimental alterations of body composition, which contribute to worsening their cardio-metabolic risk profile. In addition, the reduced GH secretion may result in reduced serum insulin-like growth factor (IGF)-1 levels, and the concordance of low peak GH and low IGF-1 identify a subset of obese individuals with high cardiovascular risk. Furthermore, after weight loss, the normalization of the GH response and IGF-1 levels may or may not occur, and in patients undergoing bariatric surgery the persistence of a low GH status may affect the post-operative outcomes. In this review, we will provide an overview on some clinically relevant aspects of the relationship between obesity axis and the somatotropic axis in the light of the recently published research

Is arginine test a reliable tool for differential diagnosis of multiple system atrophy?

Arginine test for differential diagnosis of multiple system atrophy