Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas – recently defined as possible autonomous cortisol secretion (pACS) – has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking. Subjects and methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind. Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 nonfunctioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMIBSA) was increased in pACS compared to NFA (P=0.006) and mildly correlated to the post-DST cortisol level (rho=0.347; P=0.004). The post-DST cortisol levels explained up to 13.7% of LVMIBSAvariance (P=0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P=0.001) and worse arterial stiffness assessed by pulse wave velocity (P=0.033). Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition

Testicular dysfunction in 47, XXY boys: when it all begins. A semi-longitudinal study

Objective: Klinefelter syndrome is the most common chromosomal disorder in males, and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal and quantitative ultrasound data in a life-course perspective. Design: Prospective semi-longitudinal study. Methods: We included 155 subjects with 47, XXY karyotype (age range: 7 months - 55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal and testicular ultrasound assessments were performed. Results: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/FSH ratio thereafter. The Testosterone/LH ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. Conclusions: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients

Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) – Proceedings from the SOGLI consortium meeting in rome November 2022

The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched the Sarcopenic Obesity Global Leadership Initiative (SOGLI) to reach expert consensus on a definition and diagnostic criteria for Sarcopenic Obesity (SO). The present paper describes the proceeding of the Sarcopenic Obesity Global Leadership Initiative (SOGLI) meeting that was held on November 25th and 26th, 2022 in Rome, Italy. This consortium involved the participation of 50 researchers from different geographic regions and countries. The document outlines an agenda advocated by the SOGLI expert panel regarding the pathophysiology, screening, diagnosis, staging and treatment of SO that needs to be prioritized for future research in the field

Lithium-Metal Batteries Using Sustainable Electrolyte Media and Various Cathode Chemistries

Lithium-metal batteries employing concentrated glyme-based electrolytes and two different cathode chemistries are herein evaluated in view of a safe use of the highly energetic alkali-metal anode. Indeed, diethylene-glycol dimethyl-ether (DEGDME) and triethylene-glycol dimethyl-ether (TREGDME) dissolving lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium nitrate (LiNO3) in concentration approaching the solvents saturation limit are used in lithium batteries employing either a conversion sulfur-tin composite (S:Sn 80:20 w/w) or a Li+(de)insertion LiFePO4cathode. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) clearly show the suitability of the concentrated electrolytes in terms of process reversibility and low interphase resistance, particularly upon a favorable activation. Galvanostatic measurements performed on lithium-sulfur (Li/S) batteries reveal promising capacities at room temperature (25 °C) and a value as high as 1300 mAh gS-1for the cell exploiting the DEGDME-based electrolyte at 35 °C. On the other hand, the lithium-LiFePO4(Li/LFP) cells exhibit satisfactory cycling behavior, in particular when employing an additional reduction step at low voltage cutoff (i.e., 1.2 V) during the first discharge to consolidate the solid electrolyte interphase (SEI). This procedure allows a Coulombic efficiency near 100%, a capacity approaching 160 mAh g-1, and relevant retention particularly for the cell using the TREGDME-based electrolyte. Therefore, this work suggests the use of concentrated glyme-based electrolytes, the fine-tuning of the operative conditions, and the careful selection of active materials chemistry as significant steps to achieve practical and safe lithium-metal batteries

Effects of percutaneous varicocele repair on testicular volume: Results from a 12-month follow-up

Varicocele is a common finding in men. Varicocele correction has been advocated for young patients with testicular hypotrophy, but there is a lack of morphofunctional follow-up data. We assessed whether percutaneous treatment of left varicocele is associated with testicular "catch-up growth" in the following 12 months by retrospectively reviewing data from an electronic database of 10 656 patients followed up in our clinic between 2006 and 2016. We selected all young adults (<35 years) with left varicocele who underwent percutaneous treatment, had a minimum of 12 months' ultrasound imaging follow-up, and had no other conditions affecting testicular volume. One hundred and fourteen men (meanstandard deviation [s.d.] of age: 22.8 +/- 5.4 years) met the inclusion and exclusion criteria. Left testicular hypotrophy (LTH), defined as a >= 20% difference between left and right testicular volume at baseline, was observed in 26 (22.8%) men. Participants with LTH (mean +/- s.d.: 14.5 +/- 2.7 ml) had lower baseline testicular volume compared to those without LTH (mean +/- s.d.: 15.7 +/- 3.8 ml; P = 0.032). Repeated measures mixed models showed a significant interaction between LTH and time posttreatment when correcting for baseline left testicular volume (beta = 0.114, 95% confidence interval [CI]: 0.018-0.210, P = 0.020), resulting in a catch-up growth of up to 1.37 ml per year (95% CI: 0.221-2.516). Age at intervention was also associated with reduced testicular volume (-0.072 ml per year, 95% CI: -0.135-0.009; P = 0.024). Percutaneous treatment of left varicocele in young adults with LTH can result in catch-up growth over 1 year of follow-up. The reproductive and psychological implications of these findings need to be confirmed in longer and larger prospective studies

Late-onset hypogonadism: reductio ad absurdum of the cardiovascular risk-benefit of testosterone replacement therapy

Background: Low testosterone (T) level is considered a marker of poor cardiovascular health. Ten years ago, the Testosterone in Older Men with Mobility Limitations (TOM) trial was discontinued due to a higher number of adverse events in men receiving T compared with placebo. Since then, several studies have investigated the risks of T replacement therapy (TRT) in late-onset hypogonadism (LOH). Objective: To review the mechanism by which TRT could damage the cardiovascular system. Materials and methods: Comprehensive literature search of recent clinical and experimental studies. Results: The mechanisms of T-mediated coronary vasodilation were reviewed with emphasis on calcium-activated and ATP-sensitive potassium ion channels. We showed how T regulates endothelial nitric oxide synthase (eNOS) and phosphoinositide 3-kinase/protein kinase B/eNOS signaling pathways in vessel walls and its direct effects on cardiomyocytes via β1-adrenergic and ryanodine receptors and provided data on myocardial infarction and heart failure. Vascular smooth muscle senescence could be explained by the modulation of growth factors, matrix metalloproteinase-2, and angiotensin II by T. Furthermore, leukocyte trafficking, facilitated by changes in TNF-α, could explain some of the effects of T on atheromatous plaques. Conflicting data on prothrombotic risk linked to platelet aggregation inhibition via NO-triggered arachidonate synthesis or increased aggregability due to enhanced thromboxane A in human platelets provide evidence regarding the hypotheses on plaque maturation and rupture risk. The effects of T on cardiac electrophysiology and oxygen delivery were also reviewed. Discussion: The effects of TRT on the cardiovascular system are complex. Although molecular studies suggest a potential benefit, several clinical observations reveal neutral or occasionally detrimental effects, mostly due to confounding factors. Conclusions: Attempts to demonstrate that TRT damages the cardiovascular system via systematic analysis of the putative mechanisms led to the contradiction of the initial hypothesis. Current evidence indicates that TRT is safe once other comorbidities are addressed