Anorexia Nervosa and Bone.

Anorexia nervosa (AN), a psychiatric disorder characterized by altered body image, food restriction and low body weight, is associated with low bone mineral density and increased fracture risk. Despite broadening the definition of AN in the Diagnostic and Statistical Manual of Mental Disorders, 5 edition, the prevalence of low bone mass remains high, suggesting we continue to capture individuals at high risk for bone loss. Many of the endocrine disturbances adaptive to the state of chronic starvation are thought to be causal in impaired skeletal integrity in females and males with AN.

Differences in Trabecular Plate and Rod Structure in Premenopausal Women Across the Weight Spectrum.

Context: Premenopausal women with anorexia nervosa (AN) and obesity (OB) have elevated fracture risk. More plate-like and axially aligned trabecular bone, assessed by individual trabeculae segmentation (ITS), is associated with higher estimated bone strength. Trabecular plate and rod structure has not been reported across the weight spectrum.

A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women With Anorexia Nervosa.

Context: Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity.

Objective: To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN.

Plasma Free Cortisol in States of Normal and Altered Binding Globulins: Implications for Adrenal Insufficiency Diagnosis.

Context: Accurate diagnosis of adrenal insufficiency is critical because there are risks associated with overdiagnosis and underdiagnosis. Data using liquid chromatography tandem mass spectrometry (LC/MS/MS) free cortisol (FC) assays in states of high or low cortisol-binding globulin (CBG) levels, including cirrhosis, critical illness, and oral estrogen use, are needed.

Design: Cross-sectional.

Suboptimal bone microarchitecure in adolescent girls with obesity compared to normal-weight controls and girls with anorexia nervosa.

Background: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity.

Objective: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB.

Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant/restrictive food intake disorder.

Objective: Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders.

Design: Cross-sectional: two centres.

Insulin resistance since early adulthood and appendicular lean mass in middle-aged adults without diabetes: 20 years of the CARDIA study.

Aims: To determine the association between 20-year trajectories in insulin resistance (IR) since young adulthood and appendicular lean mass (ALM) at middle-age in adults without diabetes.

Methods: A prospective cohort study was designed among young and middle-aged US men (n = 925) and women (n = 1193). Fasting serum glucose and insulin were measured five times in 1985-2005.

Sex differences in body composition and association with cardiometabolic risk.

Background: Body composition differs between men and women, with women having proportionally more fat mass and men more muscle mass. Although men and women are both susceptible to obesity, health consequences differ between the sexes. The purpose of our study was to assess sex differences in body composition using anatomic and functional imaging techniques, and its relationship to cardiometabolic risk markers in subjects with overweight/obesity.

The effect of growth hormone on bioactive IGF in overweight/obese women.

Objective: Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH.

Neuroactive Steroids and Affective Symptoms in Women Across the Weight Spectrum.

3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective comorbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum.

Body Composition and Ectopic Lipid Changes With Biochemical Control of Acromegaly.

Context: Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis.

Objective: The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly.

Design: Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls.

Impaired bone strength estimates at the distal tibia and its determinants in adolescents with anorexia nervosa.

Background: Altered bone microarchitecture and higher marrow adipose tissue (MAT) may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while 1H-magnetic resonance spectroscopy (1H-MRS) allows MAT evaluation. We have reported impaired microarchitecture at the non-weight bearing radius in adolescents with anorexia nervosa (AN) and that these changes may precede aBMD deficits.

Oxytocin and Its Relationship to Body Composition, Bone Mineral Density, and Hip Geometry Across the Weight Spectrum.

Context: Oxytocin (OXT), an anorexigenic hypothalamic hormone anabolic to bone, may reflect energy availability. Basal serum OXT levels are lower in anorexia nervosa (AN, state of energy deficit) than healthy controls (HC) and negatively associated with spine bone mineral density (BMD). Reports are conflicting regarding OXT levels in overweight/obesity (OB, state of energy excess).

The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease.

Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies.

The endocrine manifestations of anorexia nervosa: mechanisms and management.

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated.

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa.

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.

Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5.

Objective: DSM-5 revised the diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of "atypical AN" for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal, DSM-5 criteria.

Method: Cross-sectional study of 168 women, 18 - 45y: (1) AN by DSM-IV (DSM-IV AN) (n = 37), (2) AN by DSM-5 but not DSM-IV criteria (DSM-5 AN) (n = 33), (3) atypical AN (ATYPICAL AN) (n = 77), (4) healthy comparison group (HC) (n = 21).

Body composition predictors of skeletal integrity in obesity.

Objective: To determine body composition predictors of skeletal integrity in overweight/obese subjects using dual energy X-ray absorptiometry (DXA). We hypothesized that visceral adiposity would be negatively, and lean mass positively, associated with DXA measures of skeletal integrity in obesity.

Materials And Methods: Our study was institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant and written informed consent was obtained.

Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women.

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.

Cortisol Measures Across the Weight Spectrum.

Context: There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated.

Objective: This study aimed to investigate cortisol measures across the weight spectrum.

Multicenter clinical experience with the Afirma gene expression classifier.

Background: Increasingly, patients with thyroid nodule cytology labeled atypical (or follicular lesion) of undetermined significance (AUS/FLUS) or follicular neoplasm (FN) undergo diagnostic analysis with the Afirma gene expression classifier (GEC). No long-term, multisite analysis of Afirma GEC performance has yet been performed.

Methods: We analyzed all patients who had received Afirma GEC testing at five academic medical centers between 2010 and 2013.