1,721,161 research outputs found
Adrenal incidentaloma.
No full textAdrenal incidentaloma is a common clinical problem and its prevalence, in radiological studies, comes close to that of autoptic data as a result of imaging technological advances. The diagnostic challenge is to distinguish the majority of benign lesions from other masses, either malignant or hormone secreting, which require further therapy. The imaging evaluation (unenhanced CT and MRI) can differentiate malignant to benign lesions because the benign lesions have high lipid content. All patients should be tested for hypercortisolism and pheochromocytoma whereas aldosteronism should be tested in hypertensive patients only. The optimal diagnostic management for adrenal incidentaloma is still controversial, and the endocrinologist must devise a cost-effective approach taking into account the extensive endocrine work-up and imaging investigations that may be necessary. A tailored strategy may be based on the selection of patients at increased risk who require a careful and extensive follow-up among the vast majority of patients who require a simplified follow-up
Pasireotide for the treatment of Cushing's disease.
No full textImportance of the field: It is important to treat patients with Cushing's disease as rapidly as possible to limit both the mortality and morbidity of the disease. Pituitary surgery remains the treatment of choice, but the rate of cure at long-term follow-up is suboptimal and recurrence rates are high. If surgery fails or relapse occurs, no treatment has proven to be fully satisfactory. Currently available medical therapies are considered a transient and palliative treatment. However, recently there has been renewed interest in medical therapy due to new insights in pathogenetic mechanisms of corticotroph pituitary tumors.
Areas covered in this review: We summarize the pharmacodynamics and possible mechanism of action of pasireotide (SOM230), a novel multireceptor-targeted somatostatin analogue. Pasireotide has a unique binding profile, with high affinity for four of the five somatostatin receptors, especially SSTR(5), the receptor most prevalent in corticotroph tumors.
What the reader will gain: The reader should gain an understanding of preclinical and clinical data supporting the potential use of pasireotide in patients with Cushing's disease.
Take home message: Preliminary data suggest that pasireotide shows promise as a tumor-targeted medical therapy in patients with Cushing's disease. If the efficacy of pasireotide is confirmed by larger studies, this compound may be a useful treatment option not only in patients with severe Cushing's disease, but also in patients with mild hypercortisolism where its efficacy might be more evident
New treatment guidelines on Cushing's disease.
No full textIt is important to treat patients with Cushing's disease as rapidly as possible to limit its long-term mortality and morbidity. Selective transphenoidal pituitary adenomectomy remains the treatment of choice but, unfortunately, the rate of cure at long-term follow-up is suboptimal and recurrences are high, even in the hands of expert neurosurgeons. Treatment options for persistent or relapsed disease include repeat trasphenoidal pituitary surgery, radiotherapy or bilateral adrenalectomy. Medical treatment, a second-line treatment option, may have either a primary or adjunctive role if the patient cannot safely undergo surgery, if surgery fails, or if the tumor recurs. Cabergoline and pasireotide (SOM230), two pituitary tumor-directed drugs, are the most exciting news in the human pharmacological approach. However, the use of these drugs in clinical practice and their real impact in the management of patients is yet to be determined. The treatment of patients with Cushing's disease is complex and requires a multidisciplinary and individualized approach to patient management using cost-benefit analyses
Approach to the patient with possible Cushing's syndrome
Full text linkClinical decision making for patients with suspect hypercortisolism involves a complex diagnostic assessment. Cushing's syndrome remains one of the most challenging endocrine pathologies. Most clinical features overlap with those of common diseases found in the general population, and some patients have an atypical clinical presentation with only isolated symptoms. Recently, several studies have suggested that the prevalence of Cushing's syndrome is higher than previously thought. Therefore, efficient screening tests are needed to identify the few uncovered patients also among unselected high-risk ambulatory patients with disorders potentially related to cortisol excess. The recommended diagnostic tests are 24-h urinary free cortisol, 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol. Once the diagnosis of Cushing's syndrome is established, the next step is the measurement of plasma ACTH. Then, dynamic test and appropriate imaging procedures are the most useful noninvasive investigations for the differential diagnosis. Patients with Cushing's disease are generally responsive to the CRH test and to high-dose glucocorticoid feedback. Bilateral inferior petrosal sinus sampling is considered the gold standard for establishing the origin of ACTH secretion, and it is recommended in patients with ACTH-dependent Cushing's syndrome whose clinical, biochemical, or radiological studies are discordant or equivocal. The present clinical case shows that even if rare, the ectopic ACTH secretion should be considered also in those cases where the pretest probability is low. The management of Cushing's syndrome depends on the exact knowledge of its various causes, paying attention to the many potential diagnostic pitfalls. The choice of test, the modality of specimen collection (blood, urine, and saliva), the quality of measurement (assay methodology and standardization), and close dialogue among endocrinologists, chemical pathologists, and neuroradiologists are key factors for optimal care of patients
Sexual Dysfunctions in Men Affected by Autoimmune Addison's Disease Before and After Short-Term Gluco- and Mineralocorticoid Replacement Therapy
No full textIntroduction. There is evidence suggesting that autoimmune Addison's disease (AD) could be associated with sexual dysfunctions probably caused by gluco- and mineralocorticoid deficiency; however, no study has yet treated this subject in males. Aim. To evaluate male sexuality and psychological correlates in autoimmune AD before and after gluco- and mineralocorticoid replacement therapy. Methods. Twelve subjects with a first diagnosis of autoimmune AD were studied before (baseline) and 2 months after (recovery phase) initiating hormone replacement therapy. Main Outcome Measures. Erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), overall satisfaction (OS), depression, and anxiety were studied using a number of questionnaires (International Index of Erectile Function, Beck Depression Inventory, and Spielberger State-Trait Anxiety Inventory); clinical, biochemical, and hormone data were included in the analysis. Results. At baseline, low values were found for EF, OF, SD, IS, and OS and high values for depression and anxiety; all of these parameters improved significantly in the recovery phase compared with baseline. EF variation between the two phases correlated significantly and positively with the variation of serum cortisol, urinary free cortisol, systolic blood pressure, and diastolic blood pressure and inversely with that of upright plasma renin activity. Multiple linear regression analysis using EF variation as dependent variable confirmed the relationship of the latter with variation of serum cortisol, urinary free cortisol, and upright plasma renin activity but not with variation of systolic and diastolic blood pressure. Conclusions. Our study showed that onset of autoimmune AD in males is associated with a number of sexual dysfunctions, all reversible after initiating replacement hormone therapy; cortisol and aldosterone deficiency seems to play an important role in the genesis of erectile dysfunction although the mechanism of their activity is not clear. Granata A, Tirabassi G, Pugni V, Arnaldi G, Boscaro M, Carani C, and Balercia G. Sexual dysfunctions in men affected by autoimmune Addison's disease before and after short-term gluco- and mineralocorticoid replacement therapy. J Sex Me
Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart.
No full textHypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expressio
Androgens in Cushing’s Syndrome
No full textAlthough polycystic ovary syndrome (PCOS) is the most common androgen excess disorder, screening for Cushing's Syndrome (CS) should be considered in women with PCOS phenotype, particularly if they are also affected by other disturbances that increase their pretest probability (e.g., osteoporosis/bone fractures). Approximately 70-80% of women with CS present menstrual abnormalities, and PCOS findings are found in 46% of these patients. Diagnostic efforts should strengthen if the clinical picture is severe or of rapid onset in order to ensure the earliest and most appropriate treatment. If the diagnosis of CS is challenging, its differentiation from PCOS is not outdone: isolated PCOS may be associated to hypothalamic-pituitary-adrenal axis disruption, leading to false-positive results in screening tests. Because of this overlap, the diagnosis of CS is initially missed or delayed. Diagnostic utility of serum androgen assessment is controversial, but the widespread use of high-performance liquid chromatography and gas chromatography-mass spectrometry for urinary steroid profiling is showing promising results. According to the role of adrenocorticotropic hormone (ACTH) in adrenal androgen secretion, it is not surprising that the levels of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and androstenedione (A4) are generally elevated or in the upper normal range in patients with ACTH-dependent CS. Conversely, adrenal androgens are generally low in patients with cortisol-secreting adrenocortical adenoma. However, androgen-secreting adrenal tumors (adenoma and carcinoma) can be also associated with severe hyperandrogenism. Regression of hypercortisolism after treatment causes disappearance of hyperandrogenism. However, signs of androgen excess may be detectable in well-controlled CS as a result of ACTH compensatory response to certain adrenal steroidogenesis inhibitors
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