The pituitary–adrenal axis and body composition

Fernandez-Rodriguez, Eva; Stewart, Paul M.; Cooper, Mark S.

doi:10.1007/s11102-008-0098-2

Cited by 50Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersStress Responses and Cortisol

The pituitary–adrenal axis and body composition

Fernandez-Rodriguez, Eva, Stewart, Paul M., Cooper, Mark S.·2009·Pituitary

DOI 10.1007/s11102-008-0098-2

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Abstract

The activity of the pituitary-adrenal axis can profoundly impact on body composition. This is dramatically seen in Cushing's syndrome (CS) but changes in body composition are also implicated in depression and alcoholic pseudocushing's. The pathophysiological mechanisms underlying these changes remain poorly understood. Changes to body composition in CS include increased fat mass, decreased bone mass, thinning of the skin and reduced lean mass. Why these tissues are affected so dramatically is unclear. Additionally, the change in body composition between individuals varies considerably for reasons which are only now becoming evident. This paper reviews the phenotypic changes with altered pituitary-adrenal axis activity and discusses the mechanisms involved. The primary focus is on adipose, bone, muscle and skin since the most dramatic changes are seen in these tissues.

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Chronic exposure to markedly increased endogenous GC levels, as shown in patients with Cushing's syndrome, unfavourably affected body fat distribution by promoting visceral fat accumulation and hepatic steatosis.
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From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [13]

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Skin Manifestations of Cushing Disease in Children and Adolescents Before and After the Resolution of Hypercortisolemia
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RADON EXPOSURE AND LEUKAEMIA
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The effect of glucocorticoids on the myosin heavy chain isoforms’ turnover in skeletal muscle
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Glucocorticoids antagonize insulin's antiproteolytic action on skeletal muscle in humans
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Cortisol, 11β-hydroxysteroid dehydrogenase type 1 and central obesity
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Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats
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Cushing's syndrome and bone mineral density: lowest Z scores in young patients.
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Osteoporosis in Cushing�s Syndrome
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Preferential Stimulation of Abdominal Subcutaneous Lipolysis after Prednisolone Exposure in Humans
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Regulation of Glucocorticoid Receptor and Isoforms and Type I 11 -Hydroxysteroid Dehydrogenase Expression in Human Skeletal Muscle Cells: A Key Role in the Pathogenesis of Insulin Resistance?
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Spine Abnormalities and Damage in Patients Cured from Cushing's Disease
Faggiano, A., Pivonello, R., Filippella, M., Somma, C. D., Orio, F., Lombardi, G., & Colao, A. (2001) · Pituitary · doi:10.1023/a:1015362822901 · Cited by 37 · see citing works
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Interleukin-1 Receptor Antagonist Is Associated with Fat Distribution in Endogenous Cushing’s Syndrome: A Longitudinal Study
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Regulation of type IV collagen gene expression and degradation in fast and slow muscles during dexamethasone treatment and exercise
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Relationship of nonalcoholic hepatic steatosis to overnight low‐dose dexamethasone suppression test in obese individuals
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Respiratory Muscle Strength in Cushing's Syndrome
MILLS, G. H., Kyroussis, D., JENKINS, P., Hamnegård, C., Polkey, M. I., Wass, J. A. H., BESSER, G. M., Moxham, J., & Green, M. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.5.9810028 · Cited by 30 · see citing works
11β Hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle
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EFFECT OF TREATMENT OF CUSHING'S SYNDROME ON SKELETAL MUSCLE STRUCTURE AND FUNCTION
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Prior Chronic in Vivo Glucocorticoid Excess Leads to an Anabolic Phenotype and an Extension of Cellular Life Span of Skin Fibroblasts in Vitro
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A Juvenile Case of Cushing's Disease Incidentally Discovered with Multiple Bone Fractures
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Profound digital collagen atrophy: a new cutaneous presentation of adrenal-dependent Cushing's syndrome
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Cutaneous manifestations in a patient with a long-term history of untreated ACTH-dependent Cushing's syndrome.
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Skin and Cushing syndrome.
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Flagged first, then by citations

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Sorted by citations

Bone loss in inflammatory disorders
Hardy, R., & Cooper, M. S. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0568 · Cited by 365 · see citing works
“Bone loss is a common feature in this situation implying that glucocorticoids can induce bone disease in isolation (Chiodini et al. 1998, Fernandez-Rodriguez et al. 2008).”
BackgroundSelf-citation
Outcome of Cushing's disease following transsphenoidal surgery in a single center over 20 years
Hassan-Smith, Z. K., Sherlock, M., Reulen, R. C., Arlt, W., Ayuk, J., Toogood, A. A., Cooper, M. S., Johnson, A. P., & Stewart, P. M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2957 · Cited by 153 · see citing works
Self-citation
The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity
Gijsen, H. S., Crowther, N. J., Hough, F. S., & Ferris, W. F. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1211-2 · Cited by 113 · see citing works
Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial
van Raalte, D. H., Brands, M., van der Zijl, N. J., Muskiet, M. H., Pouwels, P. J. W., Ackermans, M. T., Sauerwein, H. P., Serlie, M. J., & Diamant, M. (2011) · Diabetologia · doi:10.1007/s00125-011-2174-9 · Cited by 109 · see citing works
“Finally, chronic exposure to markedly increased endogenous GC levels, as shown in patients with Cushing’s syndrome, unfavourably affected body fat distribution by promoting visceral fat accumulation and hepatic steatosis [13].”
Background
Effectiveness of medical treatment for Cushing’s syndrome: a systematic review and meta-analysis
Broersen, L. H. A., Jha, M., Biermasz, N. R., Pereira, A. M., & Dekkers, O. M. (2018) · Pituitary · doi:10.1007/s11102-018-0897-z · Cited by 101 · see citing works
Endoscopic vs. microscopic transsphenoidal surgery for Cushing’s disease: a systematic review and meta-analysis
Broersen, L. H. A., Biermasz, N. R., van Furth, W. R., de Vries, F., Verstegen, M. J. T., Dekkers, O. M., & Pereira, A. M. (2018) · Pituitary · doi:10.1007/s11102-018-0893-3 · Cited by 100 · see citing works
Diagnosis and complications of Cushing’s disease: gender-related differences
Zilio, M., Barbot, M., Ceccato, F., Camozzi, V., Bilora, F., Casonato, A., Frigo, A. C., Albiger, N., Daidone, V., Mazzai, L., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12299 · Cited by 93 · see citing works
Management of endocrine disease: mortality remains increased in Cushing's disease despite biochemical remission: a systematic review and meta-analysis
van Haalen, F. M., Broersen, L. H. A., Jorgensen, J. O., Pereira, A. M., & Dekkers, O. M. (2015) · European Journal of Endocrinology · doi:10.1530/eje-14-0556 · Cited by 103 · see citing works
Advances in the epidemiology, pathogenesis, and management of Cushing’s syndrome complications
Arnaldi, G., Mancini, T., Tirabassi, G., Trementino, L., & Boscaro, M. (2012) · Journal of Endocrinological Investigation · doi:10.1007/bf03345431 · Cited by 85 · see citing works
Protection against Glucocorticoid-Induced Damage in Human Tenocytes by Modulation of ERK, Akt, and Forkhead Signaling
Poulsen, R. C., Carr, A. J., & Hulley, P. A. (2011) · Endocrinology · doi:10.1210/en.2010-1087 · Cited by 77 · see citing works
Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis
Gardner, M. P., Lightman, S., Sayer, A. A., Cooper, C., Cooper, R., Deeg, D., Ebrahim, S., Gallacher, J., Kivimaki, M., Kumari, M., et al. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.04.016 · Cited by 72 · see citing works
“We decided to adjust our associations for BMI as a measure of adiposity but whether adiposity is secondary to a less dynamic HPA axis (Bjorntorp, 2001) or vice versa is still unclear (Fernandez-Rodriguez et al., 2009).”
Continuous corticosterone delivery via the drinking water or pellet implantation: A comparative study in mice
Gasparini, S. J., Weber, M.-C., Henneicke, H., Kim, S., Zhou, H., & Seibel, M. J. (2016) · Steroids · doi:10.1016/j.steroids.2016.10.008 · Cited by 52 · see citing works
Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells
Ahasan, M. M., Hardy, R., Jones, C. M., Kaur, K., Nanus, D. E., Juarez, M., Morgan, S., Hassan-Smith, Z. K., Bénézech, C., Caamaño, J., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34414 · Cited by 49 · see citing works
Self-citation
Long‐term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia
Mallappa, A., Nella, A. A., Sinaii, N., Rao, H., Gounden, V., Perritt, A. F., Kumar, P., Ling, A., Liu, C., Soldin, S. J., et al. (2018) · Clinical Endocrinology · doi:10.1111/cen.13813 · Cited by 45 · see citing works
Glucocorticoids, bone and energy metabolism
Cooper, M. S., Seibel, M. J., & Zhou, H. (2015) · Bone · doi:10.1016/j.bone.2015.05.038 · Cited by 45 · see citing works
“Endogenous or exogenous glucocorticoid excess is also associated with other serious clinical features such as the development of insulin resistance, impaired glucose tolerance and frank diabetes [2].”
BackgroundSelf-citation
Cushing's syndrome in the elderly: data from the European Registry on Cushing's syndrome
Amodru, V., Ferrière, A., Tabarin, A., Castinetti, F., Tsagarakis, S., Tóth, M., Feelders, R. A., Webb, S. M., Reincke, M., Netea-Maier, R. T., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad008 · Cited by 42 · see citing works
Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages: individual participant meta-analysis of five cohorts
Gardner, M. P., Lightman, S. L., Kuh, D. J., Comijs, H. C., Deeg, D. J. H., Gallacher, J., Geoffroy, M., Mika Kivimaki, B., Meena Kumari, B., Power, C., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-40566-x · Cited by 42 · see citing works
Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency: A KIMS Database Analysis
Tritos, N. A., Greenspan, S. L., King, D., Hamrahian, A., Cook, D. M., Jönsson, P. J., Wajnrajch, M. P., Koltowska-Häggstrom, M., & Biller, B. M. K. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2662 · Cited by 40 · see citing works
Microscopic versus endoscopic transsphenoidal surgery in the Leiden cohort treated for Cushing’s disease: surgical outcome, mortality, and complications
Broersen, L. H. A., van Haalen, F. M., Biermasz, N. R., Lobatto, D. J., Verstegen, M. J. T., van Furth, W. R., Dekkers, O. M., & Pereira, A. M. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1038-0 · Cited by 37 · see citing works
Pharmacological management of severe Cushing’s syndrome: the role of etomidate
Pence, A., McGrath, M., Lee, S. L., & Raines, D. E. (2022) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211058583 · Cited by 33 · see citing works
Sex Differences in Presentation but Not in Outcome for ACTH-Dependent Cushing's Syndrome
Broersen, L. H. A., van Haalen, F. M., Kienitz, T., Biermasz, N. R., Strasburger, C. J., Dekkers, O. M., & Pereira, A. M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00580 · Cited by 32 · see citing works
Fat and Bone: An Odd Couple
Kremer, R. B., & Gilsanz, V. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00190 · Cited by 27 · see citing works
“Glucocorticoids Excessive production or supre-physiological administration of GC excess results in inhibition of osteoblastogenesis and accelerated adipogenesis (108) through suppression of Wnt signaling (109) and induction of PPAR-gamma 2 expression (110).”
Background
Body Composition After Endogenous (Cushing's Syndrome) and Exogenous (Rheumatoid Arthritis) Exposure to Glucocorticoids
Resmini, E., Farkas, C., Murillo, B. D., Barahona, M. J., Vives, A. S., Martínez-Momblán, M.-A., Roig, O., Ybarra, J., Geli, C., & Webb, S. M. (2010) · Hormone and Metabolic Research · doi:10.1055/s-0030-1255032 · Cited by 24 · see citing works
Glucocorticoid-Induced Osteoporosis ? A Disorder of Mesenchymal Stromal Cells?
Hardy, R., & Cooper, M. S. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00024 · Cited by 22 · see citing works
Self-citation
Cushing's disease in older patients: Presentation and outcome
Qiao, N., Swearingen, B., & Tritos, N. A. (2018) · Clinical Endocrinology · doi:10.1111/cen.13799 · Cited by 21 · see citing works
Improvement but no normalization of quality of life and cognitive functioning after treatment for Cushing’s syndrome
Broersen, L. H. A., Andela, C. D., Dekkers, O. M., Pereira, A. M., & Biermasz, N. R. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01054 · Cited by 42 · see citing works
Predictors of the effects of 4 years of growth hormone replacement on bone mineral density in patients with adult‐onset growth hormone deficiency – a KIMS database analysis
Tritos, N. A., Hamrahian, A. H., King, D., Greenspan, S. L., Cook, D. M., Jönsson, P., Kołtowska‐Häggström, M., & Biller, B. M. K. (2012) · Clinical Endocrinology · doi:10.1111/cen.12132 · Cited by 18 · see citing works
Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension
Bauman, D. R., Whitehead, A., Contino, L. C., Cui, J., Garcia-Calvo, M. M., Gu, X., Kevin, N. J., Ma, X., Pai, L.-Y., Shah, K., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.03.011 · Cited by 16 · see citing works
The incidence of adrenal crisis in the postoperative period of HPA axis insufficiency after surgical treatment for Cushing’s syndrome
Broersen, L. H. A., van Haalen, F. M., Kienitz, T., Dekkers, O. M., Strasburger, C. J., Pereira, A. M., & Biermasz, N. R. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0202 · Cited by 15 · see citing works
Targeting 11β-hydroxysteroid dehydrogenases: a novel approach to manipulating local glucocorticoid levels with implications for rheumatic disease
Hardy, R., Seibel, M. J., & Cooper, M. S. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.03.003 · Cited by 13 · see citing works
Self-citation
Ablation of TrkB signalling in CCK neurons results in hypercortisolism and obesity
Geibel, M., Badurek, S., Horn, J. M., Vatanashevanopakorn, C., Koudelka, J., Wunderlich, C. M., Brönneke, H. S., Wunderlich, F. T., & Minichiello, L. (2014) · Nature Communications · doi:10.1038/ncomms4427 · Cited by 12 · see citing works
Role of Myofibrillar Protein Catabolism in Development of Glucocorticoid Myopathy: Aging and Functional Activity Aspects
Seene, T., & Kaasik, P. (2016) · Metabolites · doi:10.3390/metabo6020015 · Cited by 12 · see citing works
“The intensive destruction of myofibrils and degradation of contractile proteins, including MyHC IIb isoform [42], are the main reasons for reduced muscle strength, motor activity, and w akness in glucocorticoid-caused myopathic rats [11,15].”
Background
Depression and body composition among older adults
Mezuk, B. R., Golden, S. H., Eaton, W. W., & Lee, H. B. (2011) · Aging & Mental Health · doi:10.1080/13607863.2011.583631 · Cited by 10 · see citing works
“Additional prospective studies of the relationship between depression and body composition are necessary to understand the specific mechanisms of this association (eg, health behaviors such as dietary intake (Carty et al, 2011 ), physiologic alternations including hypercortisolism (Fernandez-Rodriguez, Stewart, & Coop…”
Background
Gender and magnetic resonance imaging classification-related differences in clinical and biochemical characteristics of Cushing's disease: a single-centre study
Chen, Y., Mei, X., Jian, F., Ma, Q., Chen, X., Bian, L., & Sun, Q. (2014) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.20141982 · Cited by 9 · see citing works
Recurrent Cushing Disease: An Extensive Review on Pros and Cons of Different Therapeutic Approaches
Sabahi, M., Ghasemi, P., Maroufi, S. F., Shahbazi, T., Yousefi, O., Shahtaheri, S. A., Bin-Alamer, O., Dabecco, R. M., Velasquez, N., Arce, K. M., et al. (2023) · World Neurosurgery · doi:10.1016/j.wneu.2023.01.108 · Cited by 6 · see citing works
Fine Architectonics and Protein Turnover Rate in Myofibrils of Glucocorticoid-Caused Myopathic Rats
Kaasik, P., Umnova, M. M., Alev, K., Selart, A., & Seene, T. (2012) · Journal of Interdisciplinary Histopathology · doi:10.5455/jihp.20120606081246 · Cited by 6 · see citing works
“Glucocorticoids have shown to have a potent effect on muscle contractile proteins degradation, particularly MyHCIIb isoforms [18].”
Background
Glucocorticoid Regulation of Body Composition and Metabolism
Opata, A. A., Cheesman, K. C., & Geer, E. B. (2016) · Springer eBooks · doi:10.1007/978-3-319-45950-9_1 · Cited by 6 · see citing works
Hormonal aggressiveness according to the expression of cellular markers in corticotroph adenomas
Lim, J. S., Lee, M. K., Choi, E. H., Hong, N., Jee, S. I., Kim, S. H., & Lee, E. J. (2018) · Endocrine · doi:10.1007/s12020-018-1815-x · Cited by 5 · see citing works
Repeat endoscopic endonasal transsphenoidal surgery for residual or recurrent Cushing’s disease: safety, feasibility, and success
Hanalioğlu, Ş., Gurses, M., Geçici, N. N., Baylarov, B., Işıkay, İ., Gürlek, A., & Berker, M. (2024) · Pituitary · doi:10.1007/s11102-024-01396-x · Cited by 4 · see citing works
“Hypercortisolism impacts every bodily system and is linked to elevated morbidity and mortality risks [7, 8].”
Influence of prednisolone on parameters of de novo lipogenesis and indices for stearoyl-CoA- and Δ6- desaturase activity in healthy males: A Post-hoc analysis of a randomized, placebo-controlled, double-blind trial
Pranger, I. G., van Raalte, D. H., Brands, M., Muskiet, M. H. A., Kema, I. P., Serlie, M. J. M., Diamant, M., Bakker, S. J. L., & Muskiet, F. A. J. (2018) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2018.03.009 · Cited by 3 · see citing works
Endoscopic vs microscopic transsphenoidal surgery for Cushing's disease: a systematic review and meta-analysis
Broersen, L. H. A., Biermasz, N. R., van Furth, W. R., de, V. F., Verstegen, M. J. T., Dekkers, O. M., & Pereira, A. M. (2018) · Endocrine Abstracts · doi:10.1530/endoabs.56.gp202 · Cited by 3 · see citing works
Pasireotide after Surgery for Persistent Cushing’s Disease
Păduraru, D. N., Scanteie, C. L., Bolocan, A., Andronic, O., Morar, A., Ghervan, C., Ciunt, R., Bratu, O. G., Socea, B., Dragomir, L., et al. (2019) · Medicina Moderna - Modern Medicine · doi:10.31689/rmm.2019.26.4.227 · Cited by 2 · see citing works
Chronic muscle fatigue: the role of hormonal and stress factors
Seene, T., Alev, K., & Kaasik, P. (2018) · Minerva Ortopedica e Traumatologica · doi:10.23736/s0394-3410.18.03886-9 · Cited by 1 · see citing works
Basic and clinical aspects of glucocorticoid action in bone
Zhou, H., Cooper, M. S., & Seibel, M. J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814841-9.00039-7 · Cited by 1 · see citing works
Self-citation
Lipodystrophies induites par les glucocorticoïdes : de la physiopathologie à la prise en charge
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Características metabólicas diferenciais de distintos territórios adiposos em ratos submetidos a tratamento prolongado, contínuo e excessivo com glicocorticoides: um modelo de síndrome de Cushing iatrogênica.
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Authors: Fernandez-Rodriguez, E., Stewart, P. M., & Cooper, M. S.
Affiliations: University of Birmingham (GB)
Corresponding author: Stewart, Paul M.
ORCID: Stewart, Paul M.
Cooper, Mark S.
Venue: Pituitary
Publisher: Springer Science and Business Media LLC
Published: 2008-03-07
Volume: 12
Issue: 2
Pages: 105-115
ISSN: 1386-341X (ISSN-L)
1573-7403
DOI: 10.1007/s11102-008-0098-2
OpenAlex: W2071773521
Cited by: 49
References: 110
Citations by year: 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 8 · 2018: 8 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 7
FWCI: 0.32
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Pituitary (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders: National Institute for Health and Care Research (NF-SI-0508-10356)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: pituitary-adrenal axis, body composition, Cushing's syndrome, depression, fat mass, bone mass, lean body mass, skin thinning, adipose tissue, muscle, glucocorticoids
MeSH terms: Adipose Tissue, Body Composition, Bone and Bones, Cushing Syndrome, Humans, Muscles, Pituitary-Adrenal System, Skin Physiological Phenomena

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The pituitary–adrenal axis and body composition

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