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      Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review

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          Abstract

          Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.

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          Brown adipose tissue: function and physiological significance.

          The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogenesis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
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            Identification and Importance of Brown Adipose Tissue in Adult Humans

            Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism. 2009 Massachusetts Medical Society
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              Basal metabolic rate studies in humans: measurement and development of new equations.

              CJK Henry (2005)
              To facilitate the Food and Agriculture Organization/World Health Organization/United Nations University Joint (FAO/WHO/UNU) Expert Consultation on Energy and Protein Requirements which met in Rome in 1981, Schofield et al. reviewed the literature and produced predictive equations for both sexes for the following ages: 0-3, 3-10, 10-18, 18-30, 30-60 and >60 years. These formed the basis for the equations used in 1985 FAO/WHO/UNU document, Energy and Protein Requirements. While Schofield's analysis has served a significant role in re-establishing the importance of using basal metabolic rate (BMR) to predict human energy requirements, recent workers have subsequently queried the universal validity and application of these equations. A survey of the most recent studies (1980-2000) in BMR suggests that in most cases the current FAO/WHO/UNU predictive equations overestimate BMR in many communities. The FAO/WHO/UNU equations to predict BMR were developed using a database that contained a disproportionate number--3388 out of 7173 (47%)--of Italian subjects. The Schofield database contained relatively few subjects from the tropical region. The objective here is to review the historical development in the measurement and application of BMR and to critically review the Schofield et al. BMR database presenting a series of new equations to predict BMR. This division, while arbitrary, will enable readers who wish to omit the historical review of BMR to concentrate on the evolution of the new BMR equations. BMR data collected from published and measured values. A series of new equations (Oxford equations) have been developed using a data set of 10,552 BMR values that (1) excluded all the Italian subjects and (2) included a much larger number (4018) of people from the tropics. In general, the Oxford equations tend to produce lower BMR values than the current FAO/WHO/UNU equations in 18-30 and 30-60 year old males and in all females over 18 years of age. This is an opportune moment to re-examine the role and place of BMR measurements in estimating total energy requirements today. The Oxford equations' future use and application will surely depend on their ability to predict more accurately the BMR in contemporary populations.
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                Author and article information

                Contributors
                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MD
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                26 April 2024
                26 April 2024
                : 103
                : 17
                : e37916
                Affiliations
                [a ]Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China.
                Author notes
                [* ]Correspondence: Guixia Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun, Jilin 130021, China (e-mail: gwang168@ 123456jlu.edu.cn ).
                Author information
                https://orcid.org/0000-0001-8107-616X
                Article
                MD-D-23-07831 00063
                10.1097/MD.0000000000037916
                11049756
                38669419
                617ab880-9088-4c3f-b759-ee94cf8813c2
                Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 September 2023
                : 18 November 2023
                : 26 March 2024
                Categories
                4300
                Research Article
                Narrative Review
                Custom metadata
                TRUE

                energy expenditure,pheochromocytomas and paraganglioma (ppgl)

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