Journal: Endocrine connections
Firemaster 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300, or 1,000 µg/day;) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory, and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.
Immunotherapy treatment with checkpoint inhibitors (CPI) (CTLA-4 and PD-1 inhibitors) significantly improves survival in a number of cancers. Treatment can be limited by immune-mediated adverse effects including endocrinopathies such as hypophysitis, adrenalitis, thyroiditis and diabetes mellitus. If endocrinopathies (particularly hypocortisolemia) are not recognized early, they can be fatal. The diagnosis and management of endocrinopathies can be complicated by simultaneous multi-organ immune adverse effects. Here, we present Endocrine Emergency Guidance for the acute management of the endocrine complications of checkpoint inhibitor therapy, the first specialty-specific guidance with Endocrinology, Oncology and Acute Medicine input and endorsed by the Society for Endocrinology Clinical Committee. We present algorithms for management: endocrine assessment and management of patients in the first 24 hours who present life-threateningly unwell (CTCAE grade 3-4) and the appropriate management of mild-moderately unwell patients (CTCAE grade 1-2) presenting with features compatible with an endocrinopathy. Other important considerations in relation to hypohysitis and the maintenance of glucocorticoid therapy are discussed.
Islet transplantation is currently the only minimally-invasive therapy available for patients with type 1 diabetes that can lead to insulin-independence, however it is limited to only a small number of patients. Although clinical procedures have improved in the isolation and culture of islets, a large number of islets are still lost in the pre-transplant period, limiting the success of this treatment. Moreover, current practice includes islets being prepared at specialised centers, which are sometimes remote to the transplant location. Thus, a critical point of intervention to maintain the quality and quantity of isolated islets is during transportation between isolation centers and the transplanting hospitals, during which 20-40% of functional islets can be lost. The current study investigated the use of an oxygen-permeable PDMS microwell device for long distance transportation of isolated islets. We demonstrate that the microwell device protected islets from aggregation during transport, maintaining viability and average islet size during shipping.
Nutritional rickets is a growing global public health concern despite existing prevention programs and health policies. We aimed to compare infant and childhood vitamin D supplementation policies, implementation strategies and practices across Europe and explore factors influencing adherence.
Previous studies provide evidence that HbA1c and FPG should not be considered interchangeable alternatives in the diagnosis of the same type 2 diabetes, but as indicators of its different pathogenetic subtypes. This study was conducted to determine whether a particularly high amount of glucose in either HbA1c form or in fasting plasma (FPG) would be found in diabetic patients genetically predisposed for either intensive cognitive or intensive muscle metabolic activity, respectively.
Mitochondrial dysfunction has been implicated in the development of insulin resistance, however a large variety of association and intervention studies, as well as genetic manipulations in rodents have reported contrasting results. Indeed, even 39 years after the first publication describing a relationship between insulin resistance and diminished mitochondrial function, it is still unclear if a direct relationship exists, and more importantly if changes in mitochondrial capacity are a cause or consequence of insulin resistance. This review will take a journey through the past and summarize the debate about the occurrence of mitochondrial dysfunction and its possible role in causing decreased insulin action in obesity and type 2 diabetes. Evidence will be presented from studies in various human populations, as well as rodents with genetic manipulations of pathways known to affect mitochondrial function and insulin action. Finally, we will discuss if mitochondria are a potential target for the treatment of insulin resistance.
High-intensity interval training (HIIT) improves peak power output (PPO) in sedentary aging men but has not been examined in masters endurance athletes. Therefore, we investigated whether a six-week program of low-volume HIIT would (i) improve PPO in masters athletes and (ii) whether any change in PPO would be associated with steroid hormone perturbations. Seventeen male masters athletes (60 ± 5 years) completed the intervention, which comprised nine HIIT sessions over six weeks. HIIT sessions involved six 30-s sprints at 40% PPO, interspersed with 3 min active recovery. Absolute PPO (799 ± 205 W and 865 ± 211 W) and relative PPO (10.2 ± 2.0 W/kg and 11.0 ± 2.2 W/kg) increased from pre- to post-HIIT respectively (P < 0.001, Cohen's d = 0.32-0.38). No significant change was observed for total testosterone (15.2 ± 4.2 nmol/L to 16.4 ± 3.3 nmol/L (P = 0.061, Cohen's d = 0.32)), while a small increase in free testosterone occurred following HIIT (7.0 ± 1.2 ng/dL to 7.5 ± 1.1 ng/dL pre- to post-HIIT (P = 0.050, Cohen's d = 0.40)). Six weeks' HIIT improves PPO in masters athletes and increases free testosterone. Taken together, these data indicate there is a place for carefully timed HIIT epochs in regimes of masters athletes.
Several influences modulate biochemical responses to weight-adjusted levothyroxine (L-T4) replacement dose. We conducted a secondary analysis of the relationship of L-T4 dose to TSH and FT3, using a prospective observational study examining the interacting equilibria between thyroid parameters.
The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future.
This competency framework was developed by a working group of endocrine specialist nurses with the support of the Society for Endocrinology to enhance the clinical care that adults with an endocrine disorder receive. Nurses should be able to demonstrate that they are functioning at an optimal level in order for patients to receive appropriate care. By formulating a competency framework from which an adult endocrine nurse specialist can work, it is envisaged that their development as professional practitioners can be enhanced. This is the second edition of the Competency Framework for Adult Endocrine Nursing. It introduces four new competencies on benign adrenal tumours, hypo- and hyperparathyroidism, osteoporosis and polycystic ovary syndrome. The authors and the Society for Endocrinology welcome constructive feedback on the document, both nationally and internationally, in anticipation that further developments and ideas can be incorporated into future versions.