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Introduction: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS). Design: Retrospective comparative matched case-control study. Patients & Methods: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated. Results: Compared to matched controls ACT patients had higher HbA1c levels (6.9 ± 1.4 vs. 5.5 ± 0.7 % (p < 0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2 % (p = 0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89 ± 9 vs. 79 ± 11 mmHg (p = 0.001), prevalence of LVH (41.7 vs. 1.7 % (p < 0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0 % (p = 0.03)), higher HbA1c levels (6.8 ± 1.3 vs. 5.5 ± 0.7 % (p = 0.0005)) and a higher FS (21.2 ± 9.7 vs. 12.4 ± 7.7 % (p = 0.002), OR 1.11 [1.02-1.21] (p = 0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1 % (p < 0.0001)) and HbA1c levels (6.4 ± 1.2 vs. 5.5 ± 0.8 % (p = 0.006)) were found compared to controls. Conclusion: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of different dosing intervals of lanreotide, Somatuline Autogel ® (Lan-ATG) 120 mg in patients with acromegaly, previously treated with octreotide, long-acting release (Oct-LAR). Patients and study design: Patients previously on Oct-LAR 10, 20, or 30 mg were switched to 6 repeated deep subcutaneous injections of Lan- ATG 120 mg at intervals of 56, 42, or 28 days, respectively. After the third injection, dose intervals were adjusted on the basis of insulin-like growth factor 1 (IGF-1) levels. Results: The ITT (Intention To Treat) population comprised 35 patients who received at least one dose of study medication and at least one post-baseline efficacy assessment. Overall, 62.9 % (n = 22) of patients had normalised IGF-1 levels with Lan-ATG at study end (one injection interval after the 6 th injection of Lan-ATG), which was similar to the proportion at baseline (60.0 % [n = 21]). QoL did not change from baseline to study end. Patient preference for Lan-ATG was highest in the 56-day dosing interval group: 71 % , 54 % and 41 % of the patients in the 56, 42 and 28 day groups, respectively, expressed a preference for treatment with Lan-ATG (preference for Oct- LAR: 29 % , 9 % and 35 % , respectively, while the remainder had no preference). Conclusion: Lan-ATG 120 mg injected at intervals of 56, 42 and 28 days provided equivalent hormonal control and QoL to Oct-LAR 10, 20 and 30 mg injected every 28 days, respectively. The proportion of patients preferring Lan-ATG treatment was greater in the longer injection interval groups. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy of medical treatment in patients with 21-hydroxylase deficiency is usually monitored by measurement of 17 α -hydroxyprogesterone (17OHP). Saliva instead of serum sampling offers some advantages, such as painless handling and measurement of the bioactive free hormone. This study evaluated the diagnostic validity of salivary 17OHP for monitoring medical treatment, with samples collected at 7 time points throughout a day. Subjects and Methods: Day profiles were performed in 23 adolescents and young adults with 21-hydroxylase deficiency and 43 healthy volunteers. During each profile, saliva and serum samples for 17OHP were simultaneously collected. Results: With regard to the initial day profiles, samples were pathological in 63 % (saliva) and 41 % (serum). After the first day profile 14 patients underwent adjustment of medical treatment, either because of highly elevated 17OHP levels or with the aim of dose reduction. When comparing the best with the first day profile fewer samples were pathological (saliva: 32 % vs. 71 % ; p < 0.05; serum: 21 % vs. 47 % ; n. s.), while the mean hydrocortisone equivalent dose was significantly reduced (20.09 mg vs. 27.27 mg; p < 0.01). In 53 % of profiles with controlled salivary 17OHP levels at 0700 h, the necessity for a treatment modification became only apparent when analyzing the whole day profile. Conclusion: A single 0700 h value within the reference range does not allow for a reliable assessment of therapeutic efficacy. We therefore suggest 17OHP day profiles for monitoring medical treatment. In this context, saliva analysis appears to be more sensitive in identifying patients who are inadequately treated. [ABSTRACT FROM AUTHOR]

Background: Diseases of the pituitary gland can lead to the dysfunction of individual hormonal axes and to the corresponding clinical manifestations. The diagnostic assessment of pituitary function has not yet been standardized. Methods: The members of the Neuroendocrinology Section and the Pituitary Study Group of the German Society for Endocrinology (Deutsche Gesellschaft für Endokrinologie) prepared outlines of diagnostic methods for the evaluation of each of the pituitary hormonal axes. These outlines were discussed in open session in recent annual meetings of the Section and the Study Group. Results: For the evaluation of the thyrotropic axis, basal TSH and free T4 usually suffice. For the evaluation of the gonadotropic axis in men, the testosterone level should be measured; if the overall testosterone level is near normal, then calculating the free testosterone level may be additionally useful. In women, an intact menstrual cycle is sufficient proof of normal function. In the absence of regular menstruation, measurement of the basal estradiol and gonadotropin levels aids in the diagnosis of the disturbance. For the evaluation of the adrenocorticotropic axis, the basal cortisol level may be helpful; provocative testing is in many cases necessary for precise characterization. The evaluation of the somato-tropic axis requires provocative testing. Aside from the insulin tolerance test, the GHRH-arginine test has become well established. Reference ranges normed to the body mass index (BMI) are available. Conclusion: The diagnostic evaluation of pituitary insufficiency should proceed in stepwise fashion, depending on the patient's clinical manifestations and underlying disease. For some pituitary axes, measurement of basal hormone levels suffices; for others, stimulation tests are required. In general, the performance of combined pituitary tests should be viewed with caution. [ABSTRACT FROM AUTHOR]

Measurement of sex steroids is required to evaluate gonadal function, but normative data are lacking (especially for estimates of physiologically active testosterone). Using modern immunoassays, this study established sex-specific reference ranges (2.5 % and 97.5 % percentiles) for total testosterone (TOT), bioactive testosterone Vermeulen (BTV), free androgen index (FAI), free testosterone Sartorius (FTS), free testosterone Vermeulen (FTV), and sex hormone binding globulin (SHBG). In the comparative study, subjects were grouped by age (18-30; 31-50; > 50 years), BMI ( < 25; 25-30; > 30 kg/m2), and sex. Study participants were selected in such a way that each group comprised 12 subjects (e. g., 12 males between 18 and 30 years with a BMI of < 25 kg/ m2, and so on), resulting in a total of 216 controls (108 males, 108 females; age: 40.3 ± 1.0; BMI: 27.8 ± 0.4). Multiple stepwise regression analyses were performed (covariates: age, BMI, sex), and sex-specific reference ranges were applied to 50 males (age: 46.1 ± 2.3; BMI: 27.4 ± 0.7) with suspected hypogonadism. Regression analysis identified the strongest predictor of each parameter apart from sex, resulting in age-specific (males: FAI, SHBG, BTV, FTV; females: TOT, FTS, SHBG), BMI-specific (males: TOT, FTS; females: FAI, BTV, FTV) and overall cutoffs for both sexes. In male patients, overall agreement between the results derived from the estimates (i. e., BTV, FTS, FTV) was high (with discordant results in only 4 %). In summary, if both the endocrine workup and the clinical presentation were taken into account, the newly established reference ranges allowed reliable identification of hypogonadal males. [ABSTRACT FROM AUTHOR]

Background: Patients suffering from Cushing's disease are known to be restricted due to a wide range of symptoms. Despite biochemical cure, symptoms might last life-long. These include - among well-known somatic symptoms - several neuropsychiatric symptoms that cannot be as easily tested, but lead to a serious negative impact on quality of life. We aimed to evaluate what factors diminish the self-perceived quality of life the most using 3 questionnaires visualizing those impairments. Furthermore we investigated whether there would be differences in quality of life between patients still being affected by the disease and those that are already in remission. Patients and Methods: We reviewed patient charts treated between April 2008 and June 2012 for Cushing's disease and sent 3 questionnaires to the patients for evaluation. For this purpose we used the SF-36, the BDI and the Tuebingen CD-25. 54 patients complied with our request and returned the completed questionnaires. The average time after surgery was 36 months. Results: In all 8 dimensions of the SF-36 significant differences between the patient collective and the expected age- and gender-specific scores could be observed and thus a detectable impairment in quality of life. The BDI revealed that every other patient suffering from Cushing's disease presented depressive symptoms, partially with clinical relevance. In all 6 dimensions of the Tuebingen CD-25 there were notable restrictions in patients. Those restrictions particularly concerned bodily restrictions and cognitive performance. The self-perceived quality of life of active patients was - although not statistically significant - in almost all measured fields worse than the test results of patients in remission after TSS. Conclusion: Former and active Cushing's disease patients suffer from a wide range of neuropsychiatric symptoms. Those symptoms might dominate the clinical picture and lead to a serious impairment in quality of life as well as extend periods of suffering and might persist even years after being found healthy. Therefore it is important to evaluate quality of life as an independent factor in every patient being affected by Cushing's disease and to include a holistic view in their therapy. Concomitant therapeutic measures should be accessible at any time for Cushing's disease patients as the normalization of pathologically increased laboratory values doesn't obligatory lead to an improvement of the patients subjectively felt well-being. [ABSTRACT FROM AUTHOR]

Preceding studies have indicated that aberrant expression levels rather than genetic changes of GADD45γ, MEG3, and p8 gene might play a role in the pathogenesis of pituitary adenomas. We analysed their expression in various normal human tissues and in different pituitary tumour types, and investigated GADD45γ mutations in a subset of adenomas. Absolute quantification by real-time RT-PCR was performed in 24 normal tissues as well as in 34 nonfunctioning, 24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas, 1 FSHoma, and in 6 normal pituitaries. Furthermore, we investigated the relationship between clinical data and gene expression. A subset was screened for GADD45γ mutations by single strand conformation polymorphism analysis (SSCP) and sequencing. All normal human tissues expressed GADD45γ, MEG3, and p8 mRNA. For GADD45γ, significantly lower expression levels were found in nonfunctioning adenomas compared with normal pituitary and somatotroph adenomas. P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. Expression of GADD45γ was significantly higher in pituitary adenomas of female patients. No mutation was found in the GADD45γ gene. GADD45γ, MEG3, and p8 appear to have physiological functions in a variety of human tissues. GADD45γ, MEG3, and P8 may be involved in the pathogenesis of nonfunctioning and corticotroph pituitary tumours. Female gender seems to predispose to slightly higher GADD45γ expression in pituitary adenomas. Mutations of the GADD45γ are unlikely to be involved in the pathogenesis of pituitary adenomas. Supporting Information for this article is available online at http://www.thieme-connect.de/ products [ABSTRACT FROM AUTHOR]

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone over-production. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetro-relix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors. [ABSTRACT FROM AUTHOR]

Abstract: Background: Saliva is a readily available biological fluid, making it convenient in diagnosis of diseases and in multi-sampling protocols. Several salivary steroids give a useful index of free plasma levels. Increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population has increased interest in the mineralocorticoid aldosterone. Methods: A biotinylated-aldosterone tracer and a commercially available antibody are used in a time-resolved fluorescence immunoassay (TR-FIA) to measure salivary aldosterone (SA). Saliva was collected in various multi-sampling protocols: Investigation of diurnal rhythm in healthy and PA patients, ACTH stimulation test and posture test in healthy subjects. Results: Method validation showed a sensitivity of 19ng/L and intra-/inter-assay precision between 7.2–10.1% and 8.7–15.7%, respectively. SA correlated significantly (y =0.2995x ±0.01, r 2 =0.60) to plasma aldosterone measured by a commercial radioimmunoassay. SA (median; 95%CI) was at 111 (95–127)ng/L in PA (n =84) and 50 (44–56)ng/L in healthy subjects (n =60). After change in posture, aldosterone increased in both, saliva (57 (47–63)ng/L to 95 (84–117)ng/L) and plasma (26 (26–41)ng/L to 135 (110–181)ng/L). Peak levels were reached after 1h, and were higher in females than in males. Conclusions: SA correlates well to plasma aldosterone and mirrors responses during conditions of stress. SA is significantly higher in PA, and the diurnal rhythm seen in the healthy is blunted in PA. We additionally found gender-dependent differential responses to posture, with higher increases in females. Measurement of aldosterone in saliva presents a useful and convenient method for application in multi-sampling studies. [Copyright &y& Elsevier]