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      Transient Elastography and Controlled Attenuation Parameter (CAP) in the Assessment of Liver Steatosis in Severe Adult Growth Hormone Deficiency

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          Abstract

          Non-alcoholic fatty liver disease (NAFLD) is common in patients with growth hormone deficiency (GHD). Some noninvasive techniques have been used to quantify liver fat, such as the controlled attenuation parameter (CAP).

          Objective: To evaluate CAP as a tool to identify liver steatosis and its relationship with different clinical and biochemical metabolic parameters in a group of patients with severe adult growth hormone deficiency (AGHD), and to compare the evolution of metabolic profiles after 6 months of human growth hormone (rhGH) replacement therapy in a subgroup of patients.

          Methods: Cross-sectional observational study at baseline of naive rhGH multiple pituitary hormonal deficiency (MPHD) hypopituitarism patients. A 6-month intervention clinical trial in a selected group of a non-randomized, non-controlled cohort was also applied.

          Results: Liver stiffness measurement (LSM) was normal in severe AGHD patients. CAP evaluation showed steatosis in 36.3% of baseline patients (8/22), associated with higher BMI, waist circumference, insulin, and alanine aminotransferase (ALT) levels. According to steatosis degree by CAP, child-onset growth hormone deficiency (CO-GHD) was graded as 68.75% (11/16) S0, 12.5% (2/16) S1, and 18.75% (3/16) S3, whereas AO-GHD was graded as 50% (3/6) S0, 16.66% (1/6) S2, and 33.33% S3. After 6 months of hrGH replacement, CAP measurements did not change significantly, neither on group without hepatic steatosis at baseline (194.4 ± 24.3 vs. 215.4 ± 51.3; p = 0.267) nor on the group with hepatic steatosis (297.2 ± 32.3 vs. 276.4 ± 27.8; p = 0.082). A significant improvement of body composition was observed only in the first group.

          Conclusions: We have demonstrated the importance of CAP as a non-invasive tool in the liver steatosis identification on hypopituitary patients. This method may be an important indicator of the severity of metabolic disorders in MPHD patients. In our study, no liver health modification in LSM at baseline or after 6 months of rhGH replacement was found. Longer studies can help to establish the potential repercussions of growth hormone replacement therapy on liver steatosis.

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          Age-related changes in total and regional fat distribution.

          Aging is associated with progressive changes in total and regional fat distribution that have negative health consequences. Indeed, a preferential increase in abdominal fat, in particular visceral fat, combined with a decrease in lower body subcutaneous fat are commonly cited in the literature. These age-related changes in body composition can occur independent of changes in total adiposity, body weight or waist circumference, and represent a phenotype closely associated with increased morbidity and mortality risk. Tissues such as the heart, liver and skeletal muscle in the elderly have increased fat deposition, which increases risk for insulin resistance and cardiovascular disease. Furthermore, aging is associated with increased fat content within bone marrow, which exposes the elderly to fracture risk beyond that associated with low bone mineral density alone. Many of the age-associated body compositional changes cannot be detected by simple anthropometric measures alone, and the influence of gender, race or ethnicity, and physical activity patterns on these changes is unclear. This review will explore some of these age-related changes in total and regional fat distribution. Consideration will also be given to the strengths and limitations associated with some of the anthropometric methodologies employed for assessing these changes.
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            Causes and metabolic consequences of Fatty liver.

            Type 2 diabetes and cardiovascular disease represent a serious threat to the health of the population worldwide. Although overall adiposity and particularly visceral adiposity are established risk factors for these diseases, in the recent years fatty liver emerged as an additional and independent factor. However, the pathophysiology of fat accumulation in the liver and the cross-talk of fatty liver with other tissues involved in metabolism in humans are not fully understood. Here we discuss the mechanisms involved in the pathogenesis of hepatic fat accumulation, particularly the roles of body fat distribution, nutrition, exercise, genetics, and gene-environment interaction. Furthermore, the effects of fatty liver on glucose and lipid metabolism, specifically via induction of subclinical inflammation and secretion of humoral factors, are highlighted. Finally, new aspects regarding the dissociation of fatty liver and insulin resistance are addressed.
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              Management of NAFLD: a stage-based approach.

              NAFLD is the most prevalent form of liver disease in the USA, affecting an estimated 30% of the population. The condition is associated with increased mortality related to cardiovascular disease, malignancy and liver disease. Identification of patients who might be at increased risk of adverse outcomes is critical as it is not feasible to screen all patients with suspected NAFLD. Patients with NASH, the progressive subtype of NAFLD, should be targeted for treatment, especially if they have concomitant fibrosis because such patients are more likely than those without fibrosis to have adverse outcomes. Treatment goals in patients with NAFLD vary depending on the disease stage owing to differential risk of progression and the particularities of an individual's comorbid disease. Lifestyle intervention is important for all patients irrespective of disease stage, but other therapies should be targeted to those most likely to benefit. In this Review, we highlight risk factors for disease progression and offer a stage-based treatment approach for patients with NAFLD.
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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/702048/overview
                URI : http://loop.frontiersin.org/people/706067/overview
                URI : http://loop.frontiersin.org/people/747033/overview
                URI : http://loop.frontiersin.org/people/183053/overview
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                19 June 2019
                2019
                : 10
                : 364
                Affiliations
                [1] 1Endocrinology Unit, Instituto Hospital de Base , Brasília, Brazil
                [2] 2Gastroenterology Unit, Instituto Hospital de Base , Brasília, Brazil
                [3] 3Radiology Unit, Faculty of Medicine, University of Brasilia , Brasília, Brazil
                [4] 4Pneumology Unity, Faculty of Medicine, University of Brasilia , Brasília, Brazil
                [5] 5Faculty of Medicine, University of Brasilia , Brasília, Brazil
                [6] 6Endocrinology Unit, Faculty of Medicine, University of Brasilia , Brasília, Brazil
                Author notes

                Edited by: Monica Livia Gheorghiu, Carol Davila University of Medicine and Pharmacy, Romania

                Reviewed by: Grace L. H. Wong, The Chinese University of Hong Kong, China; Nicoleta Baculescu, Carol Davila University of Medicine and Pharmacy, Romania; Dumitru Branisteanu, Grigore T. Popa University of Medicine and Pharmacy, Romania

                *Correspondence: Adriana Claudia Lopes Carvalho-Furtado adrianafurtado@ 123456terra.com.br

                This article was submitted to Pituitary Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2019.00364
                6593042
                9d399b80-2938-4e7d-bfb3-3c33be572bdc
                Copyright © 2019 Carvalho-Furtado, Carvalho-Louro, Regattieri, Rodrigues, Montenegro, Ferro, Pirangi and Naves.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 March 2019
                : 22 May 2019
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 44, Pages: 9, Words: 6674
                Funding
                Funded by: Universidade de Brasília 10.13039/100008994
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                transient elastography,controlled atenuation parameter,liver steatosis,metabolic syndrome,adult growth hormone deficiency (aghd)

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