04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=-0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in βTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients. © Georg Thieme Verlag KG Stuttgart · New York.17-Hydroxylase-deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. The aim of the work was to study clinical, biochemical, and the follow up of 17OHD patients and evaluate the function and structure of CYP17A1 mutations. Brazilian patients (three 46, XX and four 46, XY; 17±1.9 years) with combined 17-hydroxylase/17,20-lyase deficiency were evaluated. CYP17A1 gene was sequenced. Functional analysis was performed transfecting COS7 cells, which were exposed to progesterone or 17α-hydroxypregnolone substrates. Hormones were determined by RIA or LC-MS/MS.  https://www.selleckchem.com/products/mlt-748.html  Three-dimensional structural modeling was performed by Modeller software. All patients presented prepubertal female external genitalia, primary amenorrhea, hypergonadotrophic hypogonadism, hypokalemic hypertension, decreased cortisol, and increased ACTH and corticosterone levels. Five patients presented previously described mutations p.W406R/p.W406R, IVS2-2A>C/p.P428L, and p.P428L/p.P428L. Two patients presented the compound heterozygous p.G478S/p.I223Nfs*10 mutations, whose CYP17A1 activity and the three dimensional structural modeling are originally studied in this paper. CYP17A1 activity of p.G478S was 13 and 58% against progesterone and 17-hydroxypregnenolone, respectively. The p.I223Nfs*10 caused a truncated inactive protein. Three-dimensional p.G478S structural modeling showed different internal hydrophobic interaction with W313 and created an additional chain side contact with L476 residue. Due to the rarity of 17OHD, the long term follow up (15.3±3.1 years) of our patients will help endocrinologists on the management of patients with 17OHD. The mutation p.G478S/pI223Nfs*10 led to severe 17OHD and impaired CYP17A1 structure and function. The integration of in silico and in vitro analysis showed how the amino acid changes affected the CYP17A1 activity and contributed to clarify the molecular interactions of CYP17A1. © Georg Thieme Verlag KG Stuttgart · New York.Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 -16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness. © Georg Thieme Verlag KG Stuttgart · New York.The aim of the study was to evaluate the clinical impact of pre-ablation rhTSH-stimulated fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT in addition to post-therapeutic whole body radioiodine scanning in patients with intermediate to high risk differentiated thyroid carcinoma (DTC). This was a retrospective single center study including 73 patients with thyroid cancer (44 females, mean age 43.2±16.2 years, 62% papillary, 31% follicular, 7% poorly differentiated). All patients underwent ablative radioiodine treatment (mean activity 3661±673 MBq I-131) using rhTSH after thyroidectomy and lymph node (LN) dissection (01/2013-10/2016) and TSH-stimulated F-18 FDG PET/CT (4 MBq/kg body weight, low dose CT). Post-treatment I-131 whole body scan (I-131 WBS) was obtained 9 days afterwards in planar technique and in case of equivocal or abnormal findings using SPECT/CT. Thirty-one patients (42%) showed F-18 FDG avid lesions, 14 patients showed more FDG than iodine positive lesions and 5 patients more iodine positive lesions in I-131 WBS, respectively. Fifty-three patients showed identical F-18 FDG PET/CT and I-131 WBS. The initial treatment plan was changed from follow-up to therapy (surgery, systemic therapy using tyrosine-kinase inhibition) in 11 patients (15%) on the basis of F-18 FDG PET/CT imaging. Six of these 11 patients had papillary thyroid cancer. Three patients with histologically proven LN metastases had stimulated thyroglobulin-levels less then 2.0 ng/ml. Our study demonstrated a clinical benefit of pre-ablation rhTSH-stimulated F-18 FDG PET/CT imaging in about 20% of patients with intermediate to high risk DTC, leading to change in patient management in 15%. Eigentümer und Copyright ©Georg Thieme Verlag KG 2020.The objective of this scoping review was to create an up-to-date descriptive overview of published Disease-Management-Program evaluations conducted within Europe. We also assessed the methodological quality of the evaluation and the comparability of the included studies. The Databases Pub Med via Medline and Embase via Ovid were searched for thematically fitting publications. Out of 649 initial titles and abstracts, 45 full-texts were screened for inclusions. Finally, 21 publications met all inclusion criteria. DMPs from Germany, Austria, Italy, the Netherlands and Great Britain were included. The results are tabulated in the results section and discussed descriptively. Due to the heterogeneity of the included studies and the application of sometimes potentially biased study design comparisons were difficult. A uniform European-wide evaluation strategy and common quality features would be desirable. © Georg Thieme Verlag KG Stuttgart · New York.