The Journal of clinical endocrinology and metabolism
-
J. Clin. Endocrinol. Metab. · Apr 2013
ReviewClinical review: the use of vaptans in clinical endocrinology.
Hyponatremia is the most common electrolyte disorder encountered in clinical practice and represents a clinical, social, and economic burden. Conventional treatments of hyponatremia present some pitfalls, such as suboptimal efficacy, risk of overly rapid correction, and adverse effects. Vasopressin receptor antagonists, known as vaptans, represent a new and interesting class of drugs for the treatment of the euvolemic and hypervolemic forms of hyponatremia. ⋯ Vaptans can be considered a new effective tool for the treatment of euvolemic and hypervolemic hyponatremia. Nevertheless, more comparative research of vaptans vs other therapies on clinical grounds is needed to more accurately assess the value of these drugs in the treatment of hyponatremia.
-
J. Clin. Endocrinol. Metab. · Apr 2013
ReviewEndocrine side effects induced by immune checkpoint inhibitors.
In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as "immune-related adverse events," mainly including rash, colitis, hepatitis, and endocrinopathies. ⋯ Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
-
J. Clin. Endocrinol. Metab. · Apr 2013
Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.
Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. ⋯ Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.
-
J. Clin. Endocrinol. Metab. · Mar 2013
Elevated anandamide and related N-acylethanolamine levels occur in the peripheral blood of women with ectopic pregnancy and are mirrored by changes in peripheral fatty acid amide hydrolase activity.
Studies from knockout mice suggest that perturbations in oviductal endocannabinoid levels, endocannabinoid receptors, or endocannabinoid degrading enzyme [fatty acid amide hydrolase (FAAH)] expression result in infertility secondary to physical trapping of embryos. Similar observations have been made in ectopic pregnant women together with a suggestion that the endocannabinoid receptor gene polymorphism 1359G/A (rs1049353) is associated with ectopic pregnancy. These observations led to the hypothesis that ectopic pregnancy is associated with a perturbation in levels of endocannabinoids and FAAH activity and that such changes are associated with impaired tubal function. ⋯ Elevated endocannabinoid levels and reduced FAAH activity are associated with ectopic pregnancy and may modulate tubal function, suggesting dysfunctional endocannabinoid action in ectopic implantation. Oleoylethanolamide may play a critical role in embryo-tubal transport.
-
J. Clin. Endocrinol. Metab. · Mar 2013
Randomized Controlled TrialEffects of vitamin D supplementation in older African American women.
Serum 25-hydroxyvitamin D (25OHD) is lower in women with darker skin color. Is it due to lower skin production, lower absorption, or different metabolism of vitamin D? ⋯ Vitamin D3 800 IU increased serum 25OHD greater than 20 ng/mL (>50 nmol/L) in 97.5% of the African American women just as it did in the Caucasian women, and therefore, the RDA is the same for both groups. Because absorption and metabolism of oral vitamin D absorption is similar in both groups, lower levels of serum 25OHD in African Americans must be due to lower production of vitamin D in skin.