B Allolio

..Only large prospective multicentre trials comparing different treatment options will allow to make systematic progress in the management of ACC...

..Patients present with hormone excess (e.g. virilization, Cushing's syndrome) or a local mass effect (median tumor size at diagnosis > 10 cm). This paper reviews current diagnostic and therapeutic strategies in ACC...

..Because of the general availability of SPECT technology, [(123)I]IMTO scintigraphy has the potential to become a widely used tool to noninvasively characterize the biology of adrenal lesions...

..We have shown high and specific retention of [123I]metomidate ([123I]IMTO) in ACC lesions, suggesting that labeling of metomidate with 131I offers targeted radionuclide therapy for advanced ACC...

..Until the results of such trials are available DHEA cannot be considered part of standard replacement in AI, but compassionate use of DHEA in individual patients with AI and impaired well-being may be justified...

..We therefore investigated the effects of aminoglutethimide (AG), metyrapone (MTP) and etomidate (ETO) in the human NCI-h295 adrenocortical carcinoma cell line...

..We hypothesized that these results may have been affected by a referral bias because many patients may contact specialized centers only after recurrence...

..However, the pathophysiology and diagnosis criteria of relative adrenal insufficiency and its treatment remain unsettled issues...

..Inhibition of steroidogenesis is followed by increased levels of steroidogenic key proteins and reduced proliferation. These changes reflect adaptations to maintain steroidogenesis at the cost of adrenal proliferation...

..We could not detect a beneficial effect of high-dose compared to low-dose POB pretreatment on intraoperative cardiovascular stability...

..POB was the most effective drug used in monotherapy, but BP stabilization was superior using a combination of POB pretreatment with a continuous nifedipine infusion in this model...

..In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urinary steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites...

..TUD was superior to other T release preparations and represents a convenient and effective tool for T administration in experimental animals...

..Outcome of adrenal crisis is crucially determined by the physician's clinical competence and immediate initiation of specific treatment...

..These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome...

..Therapeutic approaches include weight control by dietary intervention and exercise, as well as bariatric surgery for the morbidly obese. Heart failure treatment should otherwise follow the general heart failure guidelines...

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..The pathophysiological implications of this phenomenon, however, have not been fully elucidated. This clinical study investigated the significance of low serum androgen levels in HF...

..In advanced ACC, the treatment of choice is mitotane with or without cytotoxic chemotherapy (preferably after inclusion into the FIRM-ACT trial)...

..However, in patients with an age related decline of DHEA levels, the available evidence does not support the use of DHEA replacement as an anti aging treatment...

..In conclusion, chronic anabolic T treatment causes myocardial hypertrophy under basal conditions and adversely affects left ventricular remodeling following myocardial infarction in female rats...

..The biological relevance of the changes in leptin and osteocalcin levels remains to be determined...

..Epidemiologic data from Germany indicate that more than 900,000 men are affected by osteoporotic fractures. Diagnosis and therapy of male osteoporosis are hampered by a lack of clinical studies...

..The purpose of this study was to examine whether endogenous estrogen deficiency induced by ovariectomy affects chronic left ventricular dysfunction post-myocardial infarction (MI)...

..Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency...

..In addition, for the first time, we describe a suppressive effect of CLO on steroidogenesis via inhibition of adrenal 21-hydroxylase (P450c21) activity...

..Furthermore, exact documentation of the resection status is essential for optimal decisions on treatment...

..However, because studies in female athletes are still lacking, an ergogenic activity of high-dose DHEA in this population cannot be excluded but is expected to be associated with adverse events like hirsutism, acne, and alopecia...

..This relationship remains of relevance to our understanding of carcinogenesis, but further studies are needed to address the physiological and pathological function of OPN in adrenal tissue...

..In our experience the well-educated patient often guides the physician not familiar with this disease...

..The distinct roles of 1-28-POMC and ACTH in the regulation of adrenal growth and steroidogenesis suggest that the adrenal cortex is under the dual opposing control of fragments from the same mother peptide POMC...

..However, the authors concluded that prospective investigations would be required to fully define the therapeutic potential of this important treatment option...

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..Although radiotherapy is often considered ineffective in the treatment of ACC, the limited number of available studies does not support this statement...

..Our results suggest that ZG cells, in addition to PKA and Epac/Rap proteins, contain other as yet unidentified cAMP mediator(s) involved in regulating CaMK activity and aldosterone secretion...

..Several targeted therapies are under investigation (e.g. IGF-1 inhibitors, sunitinib, sorafenib) and may lead to new treatment options...

..The prognostic significance of cortisol that may also bind and activate the mineralocorticoid receptor in chronic heart failure is unknown...

..CONCLUSIONS: Our results provide evidence for significant changes in sex steroid metabolism by human PBMCs with aging, which may represent an endocrine link to immune senescence...

..In conclusion, administration of testosterone significantly improves recovery from global ischemia. These beneficial effects are associated with an attenuation of reperfusion induced [Ca2+]i overload...

..In all patients a structured follow-up for 10 years is strongly recommended...

..This improvement, however, did not include preservation of high-energy phosphate metabolism. Other potential mechanisms include an anti-oxidant activity of 17beta-estradiol-and estrogen-induced alterations in glucose metabolism...

..Future research should focus on DHEA treatment for adrenal insufficiency, and DHEA administration in both patients receiving chronic glucocorticoid treatment and women with androgen deficiency...

..However, to date, the prognostic value of the proposed classification has not been evaluated...

..AsP may therefore play a crucial role in adrenal growth and tumourigenesis. The aim of this study was to further characterize the human homologue of AsP and its possible role in adrenal tumourigenesis...

..Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas...

..This review covers these recent molecular and clinical advances which most likely will dramatically alter the treatment of endocrine malignancies within the coming decade...

..Thus, in contrast to previous findings in adrenal insufficiency, we found no obvious benefit of 4 months of dehydroepiandrosterone supplementation in healthy men with a physiological decline of dehydroepiandrosterone production...

..Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still-limited number of reported cases, the potential benefits of octreotide treatment should be weighed carefully against its possible risks...

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..Testosterone treatment had no detrimental effects following MI. Reduced wall stress and LVEDP may even improve long-term outcome...

..The predominant receptor expressed in adrenocortical tumours is the Angiotensin II type 1 receptor whereas type 2 receptor expression is minimal...

..For the first time, patients with metastatic/unresectable ACC can participate in a prospective controlled randomized trial comparing two different cytotoxic chemotherapy regimes (FIRM-ACT)...

..In conclusion, an interdisciplinary approach with a structured use of available diagnostic tools is needed to classify adrenal tumors correctly...

..New specific imaging methods would therefore be of great clinical value. We, therefore, studied the potential of iodometomidate (IMTO) as tracer for molecular imaging of cytochrome P450 family 11B (Cyp11B) enzymes...

..However, there is no evidence for any therapy beneficial in patients failing these therapies. Therefore, we evaluated the effects of the anti-VEGF antibody bevacizumab plus capecitabine as salvage therapy in ACC...

..31 (1.80-15.62) in patients with metastatic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2.16-16.94). In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC...

..Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here, we evaluated frequency, causes and risk factors of AC in patients with chronic AI...

..These findings indicate a multifunctional role of these proteases beyond adrenal proliferation...

..Here we evaluated the subjective health status in primary and secondary AI and the effect of concomitant disease...

..The present study is in agreement with findings of previous reported studies in human subjects demonstrating beneficial effects of low glycaemic diets on glucose metabolism in patients with diabetes mellitus type 2...

..These findings will facilitate the use of the zebrafish as a model organism in the study of the physiological role of POMC-derived peptides...

..05). Taken together, these data indicate enhanced peripheral 5 alpha-reductase activity in PCOS. Thus, not only ovary and adrenal, but also liver and peripheral target tissues, significantly contribute to steroid alterations in PCOS...

..Future studies need to address the impact of more physiological treatment options like parathyroid hormone(1-34) or parathyroid transplantation on well-being and mood in these patients...

..DHEAS does not seem to represent a circulating storage pool for DHEA regeneration, and therefore serum DHEAS is unlikely to reflect bioavailable DHEA...

..We estimated the prognostic role of these risk factors in unselected patients with heart failure...

..This may lead to changes in insulin requirement in patients with primary adrenal insufficiency and type 1 diabetes. Therefore, we assessed insulin requirement in patients with autoimmune polyendocrine syndrome type 2 (APS-2)...

..Otherwise, life-threatening hypertensive crisis can be precipitated even in the previously asymptomatic patient...

..2, 95% CI 1.0-4.5, P=0.038). Our findings suggest that ERCC1 expression is the first factor for predicting survival in ACC patients treated with platinum-based chemotherapy...

..Both high blood pressure and orthostatically induced syncope improved substantially after treatment with clonidine...

..In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties...

..In conclusion, this is the first example of a human disease model based on RNA interference in rats...

..v. every 3 months) was initiated, leading to rapid disappearance of local pain. Follow-up over 24 months documented a stable clinical and radiological picture without evidence of progressive bone destruction...

..These data demonstrate a gradual transition from early pituitary-independent interrenal organogenesis to developmental control by the anterior domain of pituitary corticotrophs acting via Mc2 receptors...

..This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia...

..However, experimental sepsis in rodents leads to down-regulation of DHEA sulfotransferase, which inactivates DHEA to DHEAS, theoretically resulting in higher DHEA levels...

..Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival...

..Here we compared the results of a structured clinical assessment to the outcome of repeated, timed serum cortisol measurements...

..Thus, long-term management of patients with adrenal insufficiency remains a challenge, requiring an experienced specialist. However, all doctors should know how to diagnose and manage suspected acute adrenal failure...

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..In a mouse model which lacks all endogenous POMC peptides, s.c. treatment with synthetic 1-28 POMC alone can reduce food intake and body weight, but has no impact upon adrenal growth or steroidogenesis...

..These data show that alphaENaC expression is directly regulated by androgens in vitro and in vivo and highlight a potential mechanism explaining the reported gender differences in blood pressure...

..However, many patients have progressive disease despite treatment with these regimens...