TY - JOUR AB - OBJECTIVE: To analyze the proportion of diabetes among all hospitalized cases in Germany between 2015 and 2020. METHODS: Using the nationwide Diagnosis-Related-Groups statistics, we identified among all inpatient cases aged ≥ 20 years all types of diabetes in the main or secondary diagnoses based on ICD-10 codes, as well all COVID-19 diagnoses for 2020. RESULTS: From 2015 to 2019, the proportion of cases with diabetes among all hospitalizations increased from 18.3% (3.01 of 16.45 million) to 18.5% (3.07 of 16.64 million). Although the total number of hospitalizations decreased in 2020, the proportion of cases with diabetes increased to 18.8% (2.73 of 14.50 million). The proportion of COVID-19 diagnosis was higher in cases with diabetes than in those without in all sex and age subgroups. The relative risk (RR) for a COVID-19 diagnosis in cases with vs. without diabetes was highest in age group 40-49 years (RR in females: 1.51; in males:1.41). CONCLUSIONS: The prevalence of diabetes in the hospital is twice as high as the prevalence in the general population and has increased further with the COVID-19 pandemic, underscoring the increased morbidity in this high-risk patient group. This study provides essential information that should help to better estimate the need for diabetological expertise in inpatient care settings. AU - Auzanneau, M.* AU - Eckert, A.J.* AU - Fritsche, A. AU - Heni, M. AU - Icks, A.* AU - Mueller-Stierlin, A.* AU - Dugic, A.* AU - Risse, A.* AU - Lanzinger, S.* AU - Holl, R.W.* C1 - 67448 C2 - 54108 CY - Starling House, 1600 Bristol Parkway N, Bristol, England TI - Diabetes in all hospitalized cases in Germany 2015-2019 and impact of the first COVID-19 year 2020. JO - Endocr. Connect. VL - 12 IS - 4 PB - Bioscientifica Ltd PY - 2023 SN - 2049-3614 ER - TY - JOUR AB - OBJECTIVE: Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem-mass-spectrometry (LC MS/MS) become increasingly important for routine laboratories. However, method specific publications of reference intervals obtained from sufficiently large studies are often missing. METHODS: After validation of performance characteristics, a widely available kit for steroid analysis by LC MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11 deoxycortisol, 21 deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17 hydroxyprogesterone, 11 deoxycorticosterone, progesterone) in more than 500 blood samples from a population based study. While randomly selected from a larger cohort, the samples equally represented both sexes, and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with body mass index (BMI) was assessed. RESULTS: Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11 deoxycorticosterone and dihydrotestosterone could not be quantified in a large percentage of samples. CONCLUSIONS: The reference intervals for 9 steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC MS/MS based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile. AU - Kunz, S.* AU - Wang, X.* AU - Ferrari, U.* AU - Drey, M.* AU - Theodoropoulou, M.* AU - Schilbach, K.* AU - Reincke, M.* AU - Heier, M. AU - Peters, A. AU - Koenig, W.* AU - Zeller, T.* AU - Thorand, B. AU - Bidlingmaier, M.* C1 - 68754 C2 - 54964 CY - Starling House, 1600 Bristol Parkway N, Bristol, England TI - Age- and sex-adjusted reference intervals for steroid hormones measured by liquid chromatography‑tandem mass spectrometry (LC-MS/MS) using a widely available kit. JO - Endocr. Connect. VL - 13 IS - 1 PB - Bioscientifica Ltd PY - 2023 SN - 2049-3614 ER - TY - JOUR AB - Objective: Sex hormone-binding globulin (SHBG) and androgens have been associated with mortality in women and men, but controversy still exists. Our objective was to investigate associations of SHBG and androgens with all-cause and cause-specific mortality in men and women.Design: 1006 men and 709 peri- and postmenopausal women (age range: 45-82 years) from the German population-based KORA F4 cohort study were followed-up for a median of 8.7 years.Methods: SHBG was measured with an immunoassay, total testosterone (TT) and dihydrotestosterone (DHT) with mass-spectrometry in serum samples and we calculated free testosterone (cFT). To assess associations between SHBG and androgen levels and mortality, we calculated hazard ratios (HRs) with 95% Cls using Cox proportional-hazards models.Results: In the cohort, 128 men (12.7%) and 70 women (9.9%) died. In women, we observed positive associations of SHBG with all-cause (HR: 1.54, 95% CI: 1.16-2.04) and with other disease-related mortality (HR: 1.86, 95% CI: 1.08-3.20) and for DHT with all-cause mortality (HR: 1.32, 95% CI: 1.00-1.73). In men, we found a positive association of SHBG (HR: 1.24 95% CI: 1.00-1.54) and inverse associations of TT (HR: 0.87, 95% CI: 0.77-0.97) and cFT (HR: 0.84, 95% CI: 0.73-0.97) with all-cause mortality. No other associations were found for cause-specific mortality.Conclusions: Higher SHBG levels were associated with increased risk of all-cause mortality in men and women. Lower TT and cFT levels in men and higher DHT levels in women were associated with increased risk of all-cause mortality. Future, well-powered population-based studies should further investigate cause-specific mortality risk. AU - Schederecker, F. AU - Cecil, A. AU - Prehn, C. AU - Nano, J. AU - Koenig, W.* AU - Adamski, J. AU - Zeller, T.* AU - Peters, A. AU - Thorand, B. C1 - 58953 C2 - 48429 CY - Starling House, 1600 Bristol Parkway N, Bristol, England SP - 326–336 TI - Sex hormone-binding globulin, androgens and mortality: The KORA-F4 cohort study. JO - Endocr. Connect. VL - 9 IS - 4 PB - Bioscientifica Ltd PY - 2020 SN - 2049-3614 ER - TY - JOUR AB - Acromegaly is a rare disease due to chronic excess growth hormone (GH) and IGF-1. Aryl hydrocarbon receptor interacting protein (AIP) mutations are associated with an aggressive, inheritable form of acromegaly that responds poorly to SST2-specific somatostatin analogs (SSA). The role of pasireotide, an SSA with affinity for multiple SSTs, in patients with AIP mutations has not been reported. We studied two AIP mutation positive acromegaly patients with early-onset, invasive macroadenomas and inoperable residues after neurosurgery. Patient 1 came from a FIPA kindred and had uncontrolled GH/IGF-1 throughout 10 years of octreotide/lanreotide treatment. When switched to pasireotide LAR, he rapidly experienced hormonal control which was associated with marked regression of his tumor residue. Pasireotide LAR was stopped after >10 years due to low IGF-1 and he maintained hormonal control without tumor regrowth for >18 months off pasireotide LAR. Patient 2 had a pituitary adenoma diagnosed when aged 17 that was not cured by surgery. Chronic pasireotide LAR therapy produced hormonal control and marked tumor shrinkage but control was lost when switched to octreotide. Tumor immunohistochemistry showed absent AIP and SST2 staining and positive SST5. Her AIP mutation positive sister developed a 2.5 cm follicular thyroid carcinoma aged 21 with tumoral loss of heterozygosity at the AIP locus and absent AIP staining. Patients 1 and 2 required multi-modal therapy to control diabetes. On stopping pasireotide LAR after >10 years of treatment, Patient 1’s glucose metabolism returned to baseline levels. Long-term pasireotide LAR therapy can be beneficial in some AIP mutation positive acromegaly patients that are resistant to first-generation SSA. AU - Daly, A.F.* AU - Rostomyan, L.* AU - Betea, D.* AU - Bonneville, J.F.* AU - Villa, C.* AU - Pellegata, N.S. AU - Waser, B.* AU - Reubi, J.C.* AU - Waeber Stephan, C.* AU - Christ, E.* AU - Beckers, A.* C1 - 55648 C2 - 46512 CY - Euro House, 22 Apex Court Woodlands, Bradley Stoke, Bristol Bs32 4jt, England SP - 367–377 TI - Aip-mutated acromegaly resistant to first-generation somatostatin analogs: Long-term control with pasireotide lar in two patients. JO - Endocr. Connect. VL - 8 IS - 4 PB - Bioscientifica Ltd PY - 2019 SN - 2049-3614 ER - TY - JOUR AB - Objective: Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components.Design: The analyses included 1088 participants of the population-based KORA F4 study aged 62-81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome.Methods: The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models.Results: Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high-sensitivity C-reactive protein (OR 0.65; 95% CI 0.56-0.76 per standard deviation uromodulin; P < 0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 +/- 0.3 years ( OR 1.18; 95% CI 0.86-1.60).Conclusions: Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome. AU - Then, C. AU - Then, H.* AU - Lechner, A. AU - Huth, C. AU - Meisinger, C. AU - Heier, M. AU - Peters, A. AU - Koenig, W.* AU - Rathmann, W.* AU - Herder, C.* AU - Roden, M.* AU - Scherberich, J.* AU - Seissler, J. C1 - 57173 C2 - 47605 CY - Euro House, 22 Apex Court Woodlands, Bradley Stoke, Bristol Bs32 4jt, England SP - 1363-1371 TI - Serum uromodulin is inversely associated with the metabolic syndrome in the KORA F4 study. JO - Endocr. Connect. VL - 8 IS - 10 PB - Bioscientifica Ltd PY - 2019 SN - 2049-3614 ER - TY - JOUR AB - Inactivating germline mutations of the CDKN1B gene, encoding for the nuclear cyclin-dependent kinase inhibitor p27kip1 protein, have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without MEN1 mutations. The aim of this study was to in vitro characterize the germline CDKN1B mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by multiglandular primary hyperparathyroidism and gastro-entero-pancreatic tumors. We carried out subcellular localization experiments transfecting into eukaryotic HeLa and GH3 cell lines plasmid vectors expressing the CDKN1B wild type (wt) or mutant cDNA. Western blot studies showed that fusion proteins were expressed at equal levels. The mutated protein was shorter compared to the wt protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152/153 and 166/168. In HeLa and GH3 cells wt p27 localized in the nucleus whereas the p27_S125X protein was retained in the cytoplasm predicting the loss of tumor suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, since wt and mutant alleles were both present by sequencing the somatic DNA. Immunohistochemistry showed a complete loss of nuclear p27 expression in the parathyroid adenoma removed by the patient at the second surgery. In conclusion, our study confirms the pathogenic role of the c.374_375delCT CDKN1B germline mutation in a patient with MEN4. AU - Pardi, E.* AU - Mariotti, S.* AU - Pellegata, N.S. AU - Benfini, K. AU - Borsari, S.* AU - Saponaro, F.* AU - Torregrossa, L.* AU - Cappai, A.* AU - Satta, C.* AU - Mastinu, M.* AU - Marcocci, C.* AU - Cetani, F.* C1 - 42832 C2 - 35367 SP - 1-8 TI - Functional characterization of a CDKN1B mutation in a Sardinian kindred with Multiple Endocrine Neoplasia type 4 (MEN4). JO - Endocr. Connect. VL - 4 IS - 1 PY - 2015 SN - 2049-3614 ER -