Publications by authors named "Klibanski A"

Objective: Anorexia nervosa (AN) is commonly associated with depression, anxiety, and deficits in socioemotional functioning. Basal levels of oxytocin, a neurohormone with antidepressant, anxiolytic, and prosocial properties, are low in women with AN. However, the relationship between oxytocin and psychopathology of AN/atypical AN has not been examined in individuals with primarily food restriction (AN/AtypAN-R) or those with restriction plus binge/purge behaviors (AN/AtypAN-BP) alone, which is important to further elucidate the neurobiology of different AN presentations.

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Unlabelled: Although bone mineral density (BMD) is decreased and fracture risk increased in anorexia nervosa, BMD does not predict fracture history in this disorder. We assessed BMD, bone microarchitecture, and bone marrow adipose tissue (BMAT) in women with anorexia nervosa and found that only BMAT was associated with fracture history.

Introduction: Anorexia nervosa (AN) is a psychiatric disorder characterized by low body weight, low BMD, and increased risk of fracture.

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Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14−25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+).

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Epigenetic modification of chromatin is involved in non-malignant pituitary neoplasia by causing abnormal expression of tumor suppressors and oncogenes. These changes are potentially reversible, suggesting the possibility of targeting tumor cells by restoring the expression of epigenetically silenced tumor suppressors. The role of the histone deacetylase (HDAC) family in pituitary tumorigenesis is not known.

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Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.

Materials And Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR.

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Background: States of chronic overnutrition and undernutrition are both associated with impaired bone health and increased fracture risk but there are no data on bone microarchitecture following short-term controlled nutritional challenges.

Objective: The purpose of our study was to evaluate the impact of short-term high-caloric feeding and fasting on bone microarchitecture. We hypothesized that both high-caloric feeding and fasting would have negative effects on microarchitecture.

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Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency.

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Background: Bone marrow adipose tissue (BMAT) plays a role in systemic energy metabolism and responds to nutritional changes. Chronic starvation as well as visceral adiposity are associated with BMAT accumulation. Two types of BMAT have been described which differ in anatomic location (proximal-regulated-rBMAT vs distal-constitutive-cBMAT) and composition (higher unsaturated lipids of cBMAT compared to rBMAT).

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BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.

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The functions of long noncoding (lnc)RNAs, such as MEG3, are defined by their interactions with other RNAs and proteins. These interactions, in turn, are shaped by their subcellular localization and temporal context. Therefore, it is important to be able to analyze the relationships of lncRNAs while preserving cellular architecture.

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Context: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.

Objective: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.

Design: Double-blind, randomized, placebo-controlled 12-month longitudinal study.

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Context: Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults.

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Neural processing of visual food stimuli is perturbated at extremes of weight. Human fMRI studies investigating diet effects on neural processing of food cues could aid in understanding altered brain activation in conditions of under- and overnutrition. In this preliminary study, we examined brain activity changes in response to 10 days of high-calorie-diet (HCD), followed by 10 days of fasting, hypothesizing that HCD would decrease activation in homeostatic and reward regions, while fasting would increase activation in homeostatic/reward regions and decrease activation of self-control regions.

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Context: The diagnosis of Cushing syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate.

Objective: To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models).

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Bone marrow adipose tissue (BMAT) resides within the bone marrow microenvironment where its function remains poorly understood. BMAT is elevated in anorexia nervosa, a disease model of chronic starvation, despite depletion of other fat depots. In addition to BMAT, the marrow microenvironment also consists of osteoblast and hematopoietic progenitors.

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Article Synopsis
  • The case report highlights the first documented instance of two synchronous pituitary adenomas in a 68-year-old woman, one producing ACTH and the other producing GH, indicating distinct molecular lineages.
  • The patient underwent surgery for a suspected combined macroadenoma and, postoperatively, confirmed the presence of both adenomas through different hormone expressions.
  • The findings suggest that these synchronous tumors may arise independently, as evidenced by their unique immunohistochemical profiles and the absence of known germline mutations.
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Sex steroid hormones and neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), play a significant neuroprotective role in memory circuitry aging. Here, we present findings characterizing the neuroprotective effects of BDNF on memory performance, as a function of sex and reproductive status in women. Participants (N = 191; mean age = 50.

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Objective: To examine all-cause mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I).

Design: Retrospective cohort analysis of data from ACROSTUDY (global surveillance study of patients with acromegaly treated with pegvisomant).

Methods: Kaplan-Meier analyses and Cox regression techniques were used to examine survival rates.

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Purpose: Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs).

Methods: We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015.

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Anorexia Nervosa and Bone.

Curr Opin Endocr Metab Res

December 2018

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.

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The neuroactive steroid 3α-5α-tetrahydroprogesterone (allopregnanolone), a metabolite of progesterone, is a positive allosteric modulator of GABA receptors, and low levels have been implicated in the etiology of mood disorders. However, it is not known whether metabolism of progesterone to allopregnanolone varies across the menstrual cycle or is low after menopause. We hypothesized that the allopregnanolone/progesterone ratio would decrease from the follicular to luteal phase.

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Unlabelled: IGF-1 and leptin are two nutritionally dependent hormones associated with low bone mass in women with anorexia nervosa. Using finite element analysis, we estimated bone strength in women with anorexia nervosa and found that IGF-1 but not leptin correlated significantly with estimated bone strength in both the radius and tibia.

Purpose: Women with anorexia nervosa, a psychiatric disorder characterized by self-induced starvation and low body weight, have impaired bone formation, low bone mass, and an increased risk of fracture.

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Background: Midkine (MDK), one of the heparin-binding growth factors, is highly expressed in multiple organs during embryogenesis. Plasma concentrations have been reported to be elevated in patients with a variety of malignancies, in adults with obesity, and in children with short stature, diabetes, and obesity. However, the concentrations in healthy children and their relationships to age, nutrition, and linear growth have not been well studied.

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Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA.

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The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs), intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (Meg3-DMR). In mice, a maternal deletion of the IG-DMR leads to LOI in the locus, proving that the IG-DMR is a cis-acting imprinting control region of the locus.

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