You are looking at 81 - 90 of 20,080 items for

  • All content x
Clear All
Restricted access

Sneha Arya, Ankita Tiwari, Anurag Ranjan Lila, Vijaya Sarathi, Vishwambhar Vishnu Bhandare, Bajarang Vasant Kumbhar, Khushnandan Rai, Ambarish Kunwar, Hemangini Thakkar, Kunal Thakkar, Saba Samad Memon, Virendra Patil, Kranti Khadilkar, Swati S Jadhav, Nalini S Shah, and Tushar Bandgar


To evaluate the pathogenic role of a few benign variants and hypomorphic pathogenic variants in SRD5A2.

Design and methods:

We retrospectively analyzed phenotypes and genotypes in 23 Indian patients with genetically proven steroid 5α-reductase 2 (SRD5A2) deficiency. The interactions of the SRD5A2 enzymes resulting due to the most common benign variant (p.Val89Leu), the most common (hypomorphic) pathogenic variant (p.Arg246Gln) and the double variants (p.Val89Leu and p.Arg246Gln) in SRD5A2 were compared with that of the wild type (WT) enzyme by molecular dynamics (MD) simulation.


The majority (n = 19, 82.61%) of patients presented for atypical genitalia and had male gender identity (16/20). Including the two novel ones (p.Leu83Pro, p.Ala28Leufs*103), a total of nine different pathogenic variants were observed. p.Arg246Gln was the most common pathogenic variant (n = 12). Homozygous p.Arg246Gln (n = 9) variant was associated with milder undervirilization (Sinnecker score of ≤3a: 8/9 vs 6/14, P = 0.04) and had concurrent homozygous p.Val89Leu in all patients. Interestingly, asymptomatic fathers of two index patients were homozygous for p.Arg246Gln which questioned the pathogenicity of the variation as a sole factor. Unlike all symptomatic homozygous p.Arg246Gln patients who were also homozygous for p.Val89Leu, asymptomatic homozygous p.Arg246Gln fathers were heterozygous for p.Val89Leu. On MD simulation SRD5A2 p.Val89Leu-Testeosterone (T) and SRD5A2 p.Arg246Gln-T complexes, but not SRD5A2 p.Val89Leu and p.Arg246Gln-T complex, demonstrated close interaction between NADPH and T as that of SRD5A2 WT-T.


p.Arg246Gln may not be pathogenic as a sole variation even in the homozygous state; additional contribution of homozygous p.Val89Leu variant may be essential for the pathogenicity of p.Arg246Gln in SRD5A2.

Restricted access

Kyriakie Sarafoglou, Mutaz M Jaber, Mahmoud Al-Kofahi, and Richard C. Brundage

not applicable

Free access

Marco Mezzullo, Guido Di Dalmazi, Alessia Fazzini, Margherita Baccini, Andrea Repaci, Alessandra Gambineri, Valentina Vicennati, Carla Pelusi, Uberto Pagotto, and Flaminia Fanelli

Restricted access

Eline Sofia van der Valk, Bibian van der Voorn, Anand M. Iyer, Sjoerd van den Berg, Mesut Savas, Yolanda B de Rijke, Erica van den Akker, Olle Melander, and Elisabeth F.C. van Rossum

Context. Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (hairF) and cortisone (hairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic- pituitary adrenal axis (HPA-axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity.

Objective. To investigate whether copeptin levels are associated with higher hairF and hairE levels in obesity.

Design. A cross-sectional study in 51 adults with obesity (body mass index ≥30 kg/m2).

Methods. Associations and interactions between copeptin, hairF, hairE, and cardiometabolic parameters were cross-sectionally analyzed.

Results. Copeptin was strongly associated with body mass index (BMI) and waist circumference (WC), (rho=0.364 and 0.530, p=0.008 and <0.001 respectively), also after correction for confounders. There were no associations between copeptin and hairF or hairE on a continuous or dichotomized scale, despite correction for confounders.

Conclusion. In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA-axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.

Free access

Teresa Porcelli, Filippo Maffezzoni, Letizia Chiara Pezzaioli, Andrea Delbarba, Carlo Cappelli, and Alberto Ferlin

Male osteoporosis has been neglected for too long time and there is need for a change. This condition is clearly under-estimated, under-diagnosed and under-treated. The diagnosis is often made late in the natural history of the pathology or even after a fracture event. Guidelines on screening politics do not agree whether and when men should be considered, and clinical trials are far less performed in men with respect to women. Actually, most of our knowledge on male osteoporosis, especially regarding treatment, is extrapolate from the female counterpart. Male osteoporosis is frequently secondary to other conditions and often associated with comorbidities. Therefore, identification of specific causes of male osteoporosis is essential to drive a correct and personalized treatment. Moreover, men have more osteoporosis-related complications and higher mortality rate associated with fractures. Furthermore, not only fewer men receive a correct and timely diagnosis, but also fewer men receive adequate treatment, and adherence to therapy is far less in men than in women. Of note, very few studies assessed the effect of antiosteoporotic treatments in men and most of them considered only bone density as primary endpoint. This review focuses on the areas that are still nebulous in male osteoporosis field, from identification of subjects who need to be evaluated for osteoporosis and screening programs dealing with primary prevention to diagnostic procedures for good estimates of bone quantity and quality and precise calculation of fracture risk and personalized treatment that take into account the pathophysiology of osteoporosis.

Restricted access

Bruno Lapauw and Jean-Marc Kaufman

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (T) therapy. As obese men often display lower serum T levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase of T prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low T predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low T are truly hypogonadal. We further describe the mechanisms underlying the bidirectional relationships of T levels with obesity and metabolic health, and finally assess the evidence for T therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum SHBG and total T levels are highly prevalent in obese men, but that only those with low free T levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low T is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound T therapy trials having shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate T therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, focus should remain on lifestyle measures and management of obesity-related consequences.

Free access

Merel M Ruissen, Anne Linde Mak, Ulrich Beuers, Maarten E Tushuizen, and Adriaan G Holleboom

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is considered the hepatic component of the metabolic syndrome and is associated with an increased risk of the development of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated comorbidities and complications, treatment requires interventions from a variety of different healthcare specialties. However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associated comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which patients suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiovascular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are ambivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidisciplinary care path development could move forward.

Restricted access

Martin Overgaard, Dorte Glintborg, Henrik Thybo Christesen, Tina Kold Jensen, and Marianne Skovsager Andersen


Low circulating prolactin is a potential marker of metabolic risk during pregnancy. We aimed to investigate associations between prolactin and glucose status in pregnant women with and without gestational diabetes mellitus (GDM) or polycystic ovary syndrome (PCOS).


Prospective observational cohort study. From the Odense Child Cohort, 1497 pregnant women were included.


Blood samples were assessed during first, second (prolactin, hemoglobin A1c (HbA1c)) and third trimester (fasting prolactin, testosterone, HbA1c, insulin, glucose). Oral glucose tolerance test (OGTT) was performed around gestation week 28 in 350 women with risk factors for GDM and in 272 randomly included women. GDM was defined by 2-h plasma glucose ≥9.0 mmol/L.


The median (IQR) prolactin increased from 633 (451–829) mIU/L in first–second trimester to 5223 (4151–6127) mIU/L at third trimester. Prolactin was inversely associated with HbA1c in first (r = −0.19, P < 0.001) and third trimester (r = −0.07, P = 0.014). In third trimester, women with GDM (n = 37; 6.0%) had lower prolactin compared to women without GDM (4269 vs 5072 mIU/L, P = 0.004). Third trimester prolactin multiple of the median (MoM) was inversely associated with risk of GDM in multivariate regression analysis (OR 0.30, P = 0.034). PCOS was diagnosed in 10.0% (n = 146). Early pregnancy prolactin MoM was positively associated to PCOS diagnosis (OR 1.38, P = 0.051).


Low prolactin levels during pregnancy were associated with higher HbA1c and risk of GDM. A diagnosis of PCOS was associated with higher early pregnancy prolactin levels.

Free access

Rolf H H Groenwold and Olaf M Dekkers

The validity of any biomedical study is potentially affected by measurement error or misclassification. It can affect different variables included in a statistical analysis, such as the exposure, the outcome, and confounders, and can result in an overestimation as well as in an underestimation of the relation under investigation. We discuss various aspects of measurement error and argue that often an in-depth discussion is needed to appropriately assess the quality and validity of a study.

Restricted access

Alessia Cozzolino, Tiziana Feola, Ilaria Simonelli, Giulia Puliani, Valeria Hasenmajer, Marianna Minnetti, Elisa Giannetta, Daniele Gianfrilli, Patrizio Pasqualetti, Andrea Lenzi, and Andrea M. Isidori

Objective: Neurosurgery is the first-line treatment for acromegaly. Whether metabolic disorders are reversible after neurosurgery is still debated. The meta-analysis aimed to address the following questions: 1) Does neurosurgery affect glycolipid metabolism? 2) Are these effects related to disease control or follow-up length?

Design: a meta-analysis and systematic review of the literature.

Methods: Three reviewers searched up databases until August 2019 for prospective trials reporting glycometabolic outcomes after neurosurgery. Three other extracted outcomes, all assessed the risk of bias.

Results: Twenty studies were included. Neurosurgery significantly reduced fasting plasma glucose (FPG) [effect size (ES) -0.57 mmol/L, 95% CI -0.82 to -0.31; P<0.001], glucose load [ES -1.10 mmol/L, 95% CI -1.66 to -0.53; p<0.001], glycosylated haemoglobin (HbA1c) [ES -0.28%, 95% CI -0.42 to -0.14; P<0.001], fasting plasma insulin (FPI) [ES -10.53 mU/L, 95% CI -14.54 to -6.51; P<0.001], homeostatic model assessment of insulin resistance (HOMA-IR) [ES -1.98, 95% CI -3.24 to -0.72; P=0.002], triglycerides (TGDs) [ES -0.28 mmol/L, 95% CI -0.36 to -0.20; P<0.001] and LDL-cholesterol (LDL-C) [ES -0.23 mmol/L, 95% CI -0.45 to -0.02 mmol/L); P=0.030] and increased HDL-cholesterol (HDL-C) [ES 0.21 mmol/L, 95% CI 0.14 to 0.28; P<0.001]. Meta-regression analysis showed that follow-up length - not disease control - had a significant effect on FPG, with the greatest reduction in the shortest follow-up (beta=0.012, SE=0.003; P=0.001).

Conclusions: Neurosurgery improves metabolism with a significant decrease in FPG, glucose load, HbA1c, FPI, HOMA-IR, TGDs, and LDL-C and increase in HDL-C. The effect on FPG seems to be more related to follow-up length than to disease control.