Journal of Clinical Endocrinology and Metabolism

CONTEXT: While the development of immune checkpoint inhibitors has transformed treatment strategies of several human malignancies, research models to study immunotherapy in ACC are lacking. OBJECTIVE: To explore the effect of anti-PD1 immunotherapy on the alteration of the immune milieu in ACC in a newly generated preclinical model and correlate with the response of the matched patient. DESIGN, SETTING AND INTERVENTION: To characterize the CU-ACC2-M2B patient-derived xenograft in a humanized mouse model, evaluate the effect of a PD-1 inhibitor therapy and compare to the CU-ACC2 patient with metastatic disease...

CONTEXT: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood. OBJECTIVE: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular eNOS content and activation. DESIGN: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet...

CONTEXT: The evidence about benefits and harms of drugs for glucocorticoid-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent glucocorticoid-induced (GI) fractures remains unclear. OBJECTIVE: To assess the comparative clinical efficacy, safety and tolerability of first-line and second-line agents in preventing GI fractures. DATA SOURCES: We searched three different databases through March 5, 2019...

CONTEXT: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves' disease (GD) by promoting auto-reactive B cell activation. OBJECTIVE: Evaluate efficacy and safety of a human, blocking, non-depleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. DESIGN: Open label, phase II proof-of-concept study. SETTING: Multicenter. PATIENTS: Fifteen with GD...

CONTEXT: A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization (IVF). Endometrial epithelial cells (EECs) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. OBJECTIVE: To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. MATERIALS AND METHODS: Human EECs were purified and cultured with different E2 concentrations (10-10, 10-9, 10-8, 10-7 M) in vitro, in which 10-7 M is supraphysiologically high...

CONTEXT: AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all seven subunit genes on adiposity, glucose- and lipid metabolism has not been systematically studied yet. OBJECTIVE: To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, total-, LDL- and HDL-cholesterol and triglycerides...

CONTEXT: Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer...

CONTEXT: Individuals with type 1 diabetes (T1DM) have alterations in brain activity which have been postulated to contribute to the adverse neurocognitive consequences of T1DM; however, the impact of T1DM and hypoglycemic unawareness on the brain's resting state activity remains unclear. OBJECTIVE: To determine whether individuals with T1DM and hypoglycemia unawareness (T1DM-Unaware) had changes in the brain resting state functional connectivity compared to healthy controls (HC) and those with T1DM and hypoglycemia awareness (T1DM-Aware)...

CONTEXT: Individuals with type 1 diabetes (T1DM) have alterations in brain activity which have been postulated to contribute to the adverse neurocognitive consequences of T1DM; however, the impact of T1DM and hypoglycemic unawareness on the brain's resting state activity remains unclear. OBJECTIVE: To determine whether individuals with T1DM and hypoglycemia unawareness (T1DM-Unaware) had changes in the brain resting state functional connectivity compared to healthy controls (HC) and those with T1DM and hypoglycemia awareness (T1DM-Aware)...

CONTEXT: The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function. METHODS: Eight electronic databases were searched for articles published up to May 8, 2018...

CONTEXT: Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer...

CONTEXT: The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function. METHODS: Eight electronic databases were searched for articles published up to May 8, 2018...

CONTEXT: Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer...

CONTEXT: AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all seven subunit genes on adiposity, glucose- and lipid metabolism has not been systematically studied yet. OBJECTIVE: To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, total-, LDL- and HDL-cholesterol and triglycerides...

CONTEXT: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves' disease (GD) by promoting auto-reactive B cell activation. OBJECTIVE: Evaluate efficacy and safety of a human, blocking, non-depleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. DESIGN: Open label, phase II proof-of-concept study. SETTING: Multicenter. PATIENTS: Fifteen with GD...

CONTEXT: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves' disease (GD) by promoting auto-reactive B cell activation. OBJECTIVE: Evaluate efficacy and safety of a human, blocking, non-depleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. DESIGN: Open label, phase II proof-of-concept study. SETTING: Multicenter. PATIENTS: Fifteen with GD...

CONTEXT: A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization (IVF). Endometrial epithelial cells (EECs) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. OBJECTIVE: To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. MATERIALS AND METHODS: Human EECs were purified and cultured with different E2 concentrations (10-10, 10-9, 10-8, 10-7 M) in vitro, in which 10-7 M is supraphysiologically high...

CONTEXT: The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function. METHODS: Eight electronic databases were searched for articles published up to May 8, 2018...

CONTEXT: Nearly one-third of all thyroid cancers are ≤ 1 cm. OBJECTIVE: Determine diagnostic pathways for microcarcinomas versus larger cancers. DESIGN/SETTING/PATIENT PARTICIPANTS: Patients from Georgia and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries with differentiated thyroid cancer diagnosed in 2014-2015 were surveyed (response rate 63%). Survey data were linked to SEER data on tumor and treatment characteristics...

CONTEXT: The thermoregulatory center in the hypothalamus is stimulated by neurokinin 3 receptor (NK3R) activation and inhibited by estrogen negative-feedback. This balance is disrupted in menopause, producing vasomotor symptoms (VMS). Objective: To evaluate safety and efficacy of the NK3R antagonist fezolinetant in menopausal VMS. Design: 12-week, double-blind, randomized, placebo-controlled study. SETTING: Eight Belgian centers from September 2015 to October 2016...