Journal of Clinical Endocrinology and Metabolism

CONTEXT: The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness. OBJECTIVE: To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness. DESIGN, PATIENTS AND METHODS: The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs)...

CONTEXT: Type 1 diabetes (T1D) is classified into three subtypes: acute onset (AT1D), slowly progressive (SP1D), and fulminant (FT1D). The differences in the type of cellular autoimmunity within each subtype remain largely undetermined. OBJECTIVE: To determine the type and frequency of islet antigen-specific CD4+ T cells in each subtype of T1D. PARTICIPANTS: Twenty patients with AT1D, 17 with SP1D, 18 with FT1D, and 17 persons without diabetes (ND)...

CONTEXT: Individual patients vary in their response to growth hormone (GH). No large scale genomewide studies have looked for genetic predictors of GH responsiveness. OBJECTIVE: To identify genetic variants associated with GH responsiveness. DESIGN: Genomewide association study. SETTING: Cohorts from multiple academic centers and a clinical trial. PATIENTS: 614 individuals receiving GH from 5 short stature cohorts: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age...

CONTEXT: Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. OBJECTIVE: To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. DESIGN, SETTING, AND PARTICIPANTS: Community dwelling women (n=811) and men (n=440) aged 60+ from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture...

OBJECTIVE: To understand PCP involvement and confidence in thyroid cancer survivorship care. DESIGN/: Setting/Participants: We surveyed PCPs identified by thyroid cancer patients from the Georgia and LA SEER registries (n=162, response rate 56%). PCPs reported their involvement in long-term surveillance and confidence in handling survivorship care (role of random thyroglobulin levels and neck ultrasound, and when to end long-term surveillance and refer back to the specialist)...

Adrenal insufficiency requires lifelong corticoid replacement therapies. However, current therapies are not able to replace the physiological circadian pattern of the adrenal cortex and are associated with many metabolic, vascular, neuroendocrine and mental perturbations. Therefore, regenerative and more curative strategies would be desirable. In the current perspective, we describe emerging new regenerative therapies for the treatment of adrenal insufficiency. Especially, we discuss gene therapy and cell replacement strategies...

CONTEXT: Mild autonomous cortisol secretion (MACS) affects up to 50% of patients with adrenal adenomas. Frailty is a syndrome characterized by the loss of physiological reserves and an increase in vulnerability, and serves as a marker of declining health. OBJECTIVE: To compare frailty in patients with MACS versus nonfunctioning adrenal tumors (NFAT). DESIGN: Retrospective study, 2003-2018. SETTING: Referral center. PATIENTS: Patients >20 YO with adrenal adenoma and MACS (1 mg overnight dexamethasone suppression (DST) of 1...

CONTEXT: Recent studies discovered a role of apolipoprotein M (apoM) in energy metabolism, and observational analyses in humans suggest an association with type 2 diabetes. The causal relationship remained however elusive. OBJECTIVE: To investigate whether reduced plasma apoM concentration are causally linked to increased risk of type 2 diabetes. DESIGN: Prospective study design analysed by mendelian randomization. SETTING AND PARTICIPANTS: Two cohorts reflecting the Danish general population: The Copenhagen City Heart Study (CCHS, n=8,589) and the Copenhagen General Population Study (CGPS; n=93,857)...

OBJECTIVE: The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice. DESIGN: The search was conducted in eight databases through June 30, 2019. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines...

CONTEXT: Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined. OBJECTIVE: To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality, and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN: Prospective cohort study. SETTING: UK Biobank...

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. OBJECTIVE: We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. DESIGN, PATIENTS, MEASURES: We studied women recruited between 1999-2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA)...

CONTEXT: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. OBJECTIVE: To investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesis. DESIGN AND INTERVENTION: FKBPL and CD44 plasma or placental concentration was determined in women pre- or post-diagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signalling...

CONTEXT: Diabetes and heart failure (HF) are two deadly and strictly related epidemic disorders. Aim of this review is to present an updated discussion of the epidemiology, pathophysiology, clinical presentation and treatment options for HF in diabetes. EVIDENCE ACQUISITION: Relevant references published up to February 2020 were identified through searches in PubMed. Quality was graded using the Newcastle-Ottawa score in observational studies and the Cochrane Collaboration's tool in randomized studies...

CONTEXT: Osteosarcopenia (loss of skeletal muscle and bone mass and/or function usually associated with aging) shares pathophysiological mechanisms with polycystic ovary syndrome (PCOS). However, the relationship between osteosarcopenia and PCOS remains unclear. OBJECTIVE: We evaluated skeletal muscle index% (SMI%=[appendicular muscle mass/weight {kg}]×100) and bone mineral density (BMD) in PCOS (hyperandrogenism+oligoamenorrhea), and contrasted these musculoskeletal markers against 3 reproductive phenotypes: (1) HA (hyperandrogenism+eumenorrhea); (2) OA (normoandrogenic+oligoamenorrhea) and, (3) controls (normoandrogenic+eumenorrhea)...

CONTEXT: It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. EVIDENCE ACQUISITION: The review is based on a collection of primary and review literature gathered from a PubMed search of hypothyroidism, levothyroxine, liothyronine, and desiccated thyroid extract, among other keywords...

Burgeoning evidence over the last 25 years has identified myriad synthetic chemicals with the capacity to alter various aspects of hormone synthesis and action. These endocrine-disrupting chemicals (EDCs) have been linked to various diseases, including reproductive disorders, metabolic diseases, and developmental abnormalities among others. Exposure to EDCs arises from industrial activity, use of personal and home care products, and consumption of contaminated food and water; however, the role of healthcare in exposing individuals to EDCs is grossly underappreciated...

IMPORTANCE: After menopause estradiol (E2) is predominately an intracrine hormone circulating in very low serum concentrations. OBJECTIVE: To examine determinants of E2 concentrations in women beyond 70 years. DESIGN AND SETTING: A cross-sectional, community based, study. PARTICIPANTS: 5325 women, mean age 75.1 (± 4.2) years, not using any sex steroid, anti-androgen/estrogen, glucocorticoid or anti-glycaemic therapy...

CONTEXT: Treatment with somatostatin receptor ligands (SRLs) is often given before pituitary surgery to patients with acromegaly. OBJECTIVE: To study whether the response to treatment with.SRLs is predictive of surgical outcome. DESIGN: Retrospective, observational study. SETTING: Tertiary care center. PATIENTS: We investigated 272 patients with acromegaly who had been treated with an SRL between 1990 and 2018...

CONTEXT: Catecholamines and adrenocortical steroids are important regulators of blood pressure. Bidirectional relationships between adrenal steroids and catecholamines have been established but whether this is relevant to patients with pheochromocytoma is unclear. OBJECTIVE: This study addresses the hypothesis that patients with pheochromocytoma and paraganglioma (PPGL) have altered steroid production compared to primary hypertensives. DESIGN: Multicenter cross-sectional study...

AIM: Reduced CaSR expression has been implicated in parathyroid tumorigenesis but the underlying mechanism remains elusive. Accordingly, we aimed to explore the epigenetic changes (DNA methylation and histone modifications) involved in CaSR regulation in sporadic parathyroid adenomas and correlate epigenetic state with disease indices. EXPERIMENTAL DESIGN: Forty sporadic parathyroid adenomas and 10 normal parathyroid tissues were studied. Real time quantitative polymerase chain reaction (qRT-PCR) for mRNA and immunohistochemistry for protein expression of CaSR were performed...