Sex-Specific Associations of Testosterone With Metabolic Traits.

Background: Testosterone levels are differentially linked with diabetes risk in men and women: lower testosterone levels in men and higher testosterone levels in women are associated with type 2 diabetes, though, the mechanisms are not fully clear. We addressed sex-specific links between testosterone and major pathogenetic mechanisms of diabetes. Methods: We analyzed data of 623 subjects (202 male, 345 female without, and 76 female with oral contraceptive therapy [OCT]) for whom insulin sensitivity and insulin secretion were assessed by oral glucose tolerance test. Body fat percentage was assessed by bioelectrical impedance. Testosterone was measured by enzyme-linked immunoassay; free testosterone and Framingham risk score were calculated. Results: There were significant interactions between testosterone and sex for all tested metabolic traits. Increasing testosterone was associated with less body fat, elevated insulin sensitivity, and reduced glycemia, independent of adiposity in men. In women without OCT, testosterone correlated with more body fat, insulin resistance, and higher glucose concentrations. Testosterone was not associated with insulin secretion in either sex, but with lower Framingham risk score in men and higher Framingham risk score in women. Conclusions: Similar to diabetes risk, insulin resistance has different association directions with testosterone levels in males and females. Insulin resistance could therefore constitute the best biological candidate linking testosterone levels and diabetes prevalence. The question of antiandrogen therapy being able to improve metabolism, glucose tolerance and cardiovascular risk in women was not clarified in our study but should be reviewed with higher numbers in a carefully matched study to reduce the influence of confounding variables.

Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization.

BACKGROUND: Based on a non-randomized study of Nigro et al. (2005) the intravenous administration of hyperimmunoglobulins (HIGs) is applied frequently to women with primary CMV-infection as "off-label use" in Germany. OBJECTIVES: In order to describe their CMV-specific neutralization-capacity in vitro, we analyzed the HIG preparations Cytotect®, and Cytogam® as well as the standard intravenous immunoglobulins (IVIG) Octagam®, Gamunex®, Kiovig®. STUDY DESIGN: We performed short-term cell-free CMV neutralization assays (CFNT) and long-term cell-adapted neutralization-plaque-reduction assays (PRANT). Human retinal epithelial cells (ARPE-19) were used as target cells. A clinical CMV primary-isolate from amnion fluid propagated in epithelial cells without any initial fibroblast adaption was used. For calibration we previously generated serum-pools (N=100) from two cohorts of mothers at birth: seronegative and latently CMV-infected mothers. Biochemical analysis included total protein, albumin, Ig-class, and IgG-subclasses. Additionally, CMV antibody-reactivity was checked using recombinant immunoblotting. RESULTS: HIG and IVIG preparations showed differences in levels and patterns of protein, Ig-class and CMV-specific antibody concentrations. All IgG-preparations showed high in vitro NT-capacity and high IgG-avidity. The NT90-values for HIGs and IVIGs and our seropositive reference-pool showed similar NT-capacity at a dilution of (1:100) which corresponded well to 4.1 PEI-Units/ml. CONCLUSION: All HIG- and IVIG-preparations showed similar NT-capacity following CMV IgG-normalization. Our in vitro results are in strong contrast to former findings suggesting higher functional CMV NT titers in IVIG-preparations compared to HIGs.

[Vaginal bleeding as symptom of a medical emergency--pitfalls of therapy with new oral anticoagulants - case 5/2014]. / Vaginale Blutung als Symptom eines internistischen Notfalls--Tücken der Therapie mit neuen oralen Antikoagulanzien - Fall 5/2014.

HISTORY AND ADMISSION FINDINGS: A 90-year-old female patient treated with dabigatran for atrial fibrillation presented emergently with a spontaneous vaginal bleeding due to endometrium carcinoma. INVESTIGATIONS: Laboratory analysis revealed azotemia consistent with acute-on-chronic renal failure. Coagulation was deranged (prolongation of activated partial thromboplastin time (aPTT) by 3.5-fold, international normalized ratio (INR) 7.8) due to a massive accumulation of dabigatran (measured plasma concentration 2230 ng/ml). DIAGNOSIS, TREATMENT AND COURSE: Vaginal bleedings were treated with external tamponade. Hemodialysis treatment was commenced due to uremia and dabigatran accumulation. Over night, the patient was dialysed with a SLED (sustained low efficiency dialysis) regimen. After volume resuscitation renal function promptly ensued indicating prerenal azotemia as a cause of renal failure. After two more hemodialysis sessions dabigatran concentrations were no longer detecable and this was paralleled by normalization of coagulation tests. CONCLUSIONS: Dabigatran can accumulate massively during acute renal failure and evoke a life-threatening bleeding diathesis. Dabigatran can be removed with low efficient dialysis (such as SLED).

Comparison of the diagnostic performance of three natriuretic peptides in hemodialysis patients: which is the appropriate biomarker?.

BACKGROUND: Plasma concentrations of natriuretic peptides are often elevated in chronic hemodialysis patients and difficult to interpret due to accumulation, high incidence of cardiac disease and changes in volume status. Mid-regional pro-ANP is a newly developed assay whereas BNP and its fragment NT-pro-BNP are available for a longer time. In this cross-sectional study, we compared the plasma concentration of MR-pro-ANP, BNP and NT-pro-BNP in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors such as residual diuresis, cardiac status and interdialytic weight gain and with mortality. METHODS AND RESULTS: In all patients enrolled, the plasma concentration of all natriuretic peptides were largely elevated with a median concentration of 337 pg/ml (interquartile range 146-684) for BNP, 4435 pg/ml (1687-16228) for NT-proBNP and 907 pmol/L (650-1298) for MR-pro-ANP. Plasma concentration of all natriuretic peptides correlated independently with age, degree of systolic dysfunction and negatively with residual diuresis. Dependency on residual renal clearance was strongest for the fragments MR-pro-ANP and NT-pro-BNP. The plasma concentration of all natriuretic peptides was associated with mortality within 2 years of follow-up. Receiver-operated curves revealed a low sensitivity (32-45%), but high specificity for all natriuretic peptides (85-93%) resulting in a high negative predictive (82-87%). Best cut-off values obtained from were 18 611 pg/ml for NT-pro-BNP, 958 pg/ml for BNP and 1684 pmol/L for MR-pro-ANP. CONCLUSIONS: In hemodialysis patients, the fragments NTproBNP and MR-pro-ANP are largely elevated compared to BNP which is explained by accumulation. The prognostic performance of MR-pro-ANP is similar to that of NT-pro-BNP or BNP.

[Two patients with renal medullary hyperechogenicity]. / Zwei Patientinnen mit echoreichen Markpyramiden.

HISTORY AND ADMISSION FINDINGS: We report two patients with medullary nephrocalcinosis and nephrolithiasis. The first patients had unspecific symptoms of a systemic inflammatory disease, the second patient was asymptomatic. INVESTIGATIONS: Both patients had normocalcemia and normal parathyroid hormone levels, very high 1,25(OH)(2)-vitamin D and normal to low 25-OH-vitamin D levels. On renal ultrasound, both patients displayed nephrocalcinosis and nephrolithiasis. DIAGNOSIS: Both patients showed dysregulation of the 1α-hydroxylase activity. The first patient suffered from a systemic inflammatory disease with consecutive activation of macrophages with extrarenal α-hydroxylase activity. The second patient had a "loss of function" mutation of the calcium sensing receptor with - for the situation - inadequatly high parathyroid hormone levels and consequently a renal dysregulation of the 1α-hydroxylase. TREATMENT AND COURSE: After immunosuppressive treatment with prednisolone and hydroxychloroquin there was complete remission of the systemic inflammatory disease in the first patient. In consequence the 1,25-(OH)(2)-vitamin D levels regressed and renal function stabilized. The second patient was completely asymptomatic with normal renal function, so far we did not initiate any treatment. CONCLUSIONS: Nephrocalcinosis and nephrolithiasis can result from hypercalciuria due to dysregulated hydroxylation of vitamin D. For both renal and extrarenal sources causal treatment is available.

Malformations in a cohort of 284 women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH).

BACKGROUND: The aim of this retrospective study was to describe the spectrum of genital and associated malformations in women with Mayer-Rokitansky-Küster-Hauser syndrome using evaluated diagnostic procedures and the Vagina Cervix Uterus Adnex - associated Malformation classification system (VCUAM). METHODS: 290 women with MRKH syndrome were clinically evaluated with using clinical examinations, abdominal and perineal/rectal ultrasound, MRI, and laparoscopy. RESULTS: Classification of female genital malformation according to the Vagina Cervix Uterus Adnex - associated Malformation classification system was possible in 284 women (97.9%). Complete atresia of Vagina (V5b) and bilateral atresia of Cervix (C2b) were found in 284 patients (100%). Uterus: bilateral rudimentary or a plastic uterine horns were found in 239 women (84.2%). Adnexa: normal Adnexa were found in 248 women (87.3%). Malformations: associated malformations were found in 126 of 282 evaluable women (44.7%), 84 women (29.6%) had malformations of the renal system. Of 284 women with Mayer-Rokitansky-Küster-Hauser syndrome 212 women (74.7%) could be classified as V5bC2bU4bA0. The most frequent classification was V5bC2bU4bA0M0 (46.8%) diagnosed in 133 of 284 women. CONCLUSIONS: Complete atresia of vagina and cervix were found in all patients, variable malformations were found with uterus and adnexa. A variety of associated malformations were present, predominantly of the renal system. It is therefore recommended that all patients with genital malformations should be evaluated for renal abnormalities.

[Rare cause of insufficient metabolic control of diabetes mellitus - Case 10/2011]. / Seltene Ursache einer unzureichenden Stoffwechseleinstellung eines Diabetes mellitus - Fall 10/2011.

HISTORY AND ADMISSION FINDINGS: A 48-year-old patient presented with an insufficient control of his diabetes mellitus which was known since 3 years. The antidiabetic medication comprised metformin and exenatide. INVESTIGATIONS: Physical examination revealed, beside elevated blood pressure, abdominal purple striae. Endocrine testing was consistent with ectopic Cushing's syndrome. Abdominal CT showed a 5 cm measuring, inhomogeneous, contrast-enhanced mass in the right suprarenal area which was positive on iodine-131 MIBG SPECT. Furthermore, urinary catecholamines were markedly increased. DIAGNOSIS, TREATMENT AND COURSE: Diagnosis of an ACTH-producing pheochromocytoma was made and an open adrenalectomy was performed. Histology confirmed a pheochromocytoma with potential aggressive clinical behaviour according to the Pheocromocytoma of the Adrenal gland Scaled Score. 6 months after the intervention, glucose control was significantly improved with an HbA1c of 5.5%. CONCLUSIONS: An ACTH-producing pheochromocytoma is a very rare cause of deterioration of glucose control. However, in presence of typical clinical findings an endocrine work-up is warranted.