Intramuscular fatty infiltration and physical function in controlled acromegaly

in European Journal of Endocrinology
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  • 1 IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Barcelona, Spain
  • 2 UAB, Bellaterra, Barcelona, Spain
  • 3 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), Barcelona, Spain
  • 4 Department of Neurology, Hospital Sant Pau, Barcelona, Spain
  • 5 Rehabilitation Unit, Hospital Sant Pau, Barcelona, Spain
  • 6 John Walton Mucular Dystrophy Research Centre, Newcastle University, International Centre for Life, Newcastle upon Tyne, Newcastle, UK
  • 7 Department of Radiology, Hospital Sant Pau, Barcelona, Spain
  • 8 Philips Healthcare, Madrid, Spain
  • 9 Universitat Internacional de Catalunya (UIC), Barcelona, Spain

Correspondence should be addressed to E Valassi Email EValassi@santpau.cat
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Introduction

Patients with acromegaly show musculoskeletal symptoms which may persist despite disease control. Increased i.m. fat fraction is a known cause of muscle dysfunction in several disorders.

Objective

To assess the degree of fat fraction in thigh muscles of controlled acromegaly patients and its relationship with muscle dysfunction.

Methods

In a cross-sectional study, we included 36 patients with controlled acromegaly and 36 matched controls. We assessed the percentage of fat fraction in each thigh muscle, using MRI 2-point Dixon sequence, and muscle performance and strength using the gait speed, timed up and go, 30-s chair stand, and hand grip strength tests. We evaluated joint symptoms using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC).

Results

Intramuscular fat fraction was greater in patients than controls (P < 0.05 for muscle compartments, rectus femoris (RF), vastus intermedius (VI), adductor magnus (AM) and semimembranosus). Patients had slower gait speed and poorer performance on the 30-s chair stand and timed up and go tests than controls (P < 0.05). The greater fat fraction in the combined anterior–posterior compartment and in each muscle was associated with worse performance on timed up and go (P < 0.05). The fat fraction in the anterior–posterior compartment predicted performance on timed up and go after adjusting for muscle area, IGF-I and WOMAC functional and pain scores (β = 0.737 P < 0.001).

Conclusions

Patients with controlled acromegaly have greater thigh i.m. fatty infiltration, which is associated with muscle dysfunction. Futures studies are needed to elucidate the mechanisms underlying this relationship.

 

     European Society of Endocrinology

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  • 1

    Reyes-Vidal CM, Mojahed H, Shen W, Jin Z, Arias-Mendoza F, Fernandez JC, Gallagher D, Bruce JN, Post KD & Freda PU Adipose tissue redistribution and ectopic lipid deposition in active acromegaly and effects of surgical treatment. Journal of Clinical Endocrinology and Metabolism 2015 100 294629 55. (https://doi.org/10.1210/jc.2015-1917)

    • Search Google Scholar
    • Export Citation
  • 2

    Moøller N & Joørgensen JOL Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocrine Reviews 2009 30 1521 77. (https://doi.org/10.1210/er.2008-0027)

    • Search Google Scholar
    • Export Citation
  • 3

    Freda PU, Shen W, Heymsfield SB, Reyes-Vidal CM, Geer EB, Bruce JN & Gallagher D Lower visceral and subcutaneous but higher intermuscular adipose tissue depots in patients with growth hormone and insulin-like growth factor I excess due to acromegaly. Journal of Clinical Endocrinology and Metabolism 2008 93 233423 43. (https://doi.org/10.1210/jc.2007-2780)

    • Search Google Scholar
    • Export Citation
  • 4

    Bredella MA, Schorr M, Dichtel LE, Gerweck AV, Young BJ, Woodmansee WW, Swearingen B & Miller KK Body composition and ectopic lipid changes with biochemical control of acromegaly. Journal of Clinical Endocrinology and Metabolism 2017 102 421842 25. (https://doi.org/10.1210/jc.2017-01210)

    • Search Google Scholar
    • Export Citation
  • 5

    Rabinowitz D, Klassen GA & Zierler KL Effect of human growth hormone on muscle and adipose tissue metabolism in the forearm of man. Journal of Clinical Investigation 1965 44 5161. (https://doi.org/10.1172/JCI105126)

    • Search Google Scholar
    • Export Citation
  • 6

    Møller N, Jørgensen JOL, Alberti KGMM, Flyvbjerg A & Schmitz O Short-term effects of growth hormone on fuel oxidation and regional substrate metabolism in normal man. Journal of Clinical Endocrinology and Metabolism 1990 70 117911 86. (https://doi.org/10.1210/jcem-70-4-1179)

    • Search Google Scholar
    • Export Citation
  • 7

    Goodpaster BH, Carlson CL, Visser M, Kelley DE, Scherzinger A, Harris TB, Stamm E & Newman AB Attenuation of skeletal muscle and strength in the elderly: the Health ABC Study. Journal of Applied Physiology 2001 90 215721 65. (https://doi.org/10.1152/jappl.2001.90.6.2157)

    • Search Google Scholar
    • Export Citation
  • 8

    Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, Simonsick EM & Harris TB Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences 2005 60 32433 3. (https://doi.org/10.1093/gerona/60.3.324)

    • Search Google Scholar
    • Export Citation
  • 9

    Diaz-Manera J, Fernandez-Torron R, LLauger J, James MK, Mayhew A, Smith FE, Moore UR, Blamire AM, Carlier PG & Rufibach L Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials. Journal of Neurology, Neurosurgery, and Psychiatry 2018 89 107110 81. (https://doi.org/10.1136/jnnp-2017-317488)

    • Search Google Scholar
    • Export Citation
  • 10

    Figueroa-Bonaparte S, Llauger J, Segovia S, Belmonte I, Pedrosa I, Montiel E, Montesinos P, Sánchez-González J, Alonso-Jiménez A & Gallardo E Quantitative muscle MRI to follow up late onset pompe patients: a prospective study. Scientific Reports 2018 8 10898. (https://doi.org/10.1038/s41598-018-29170-7)

    • Search Google Scholar
    • Export Citation
  • 11

    Wokke BH, van den Bergen JC, Versluis MJ, Niks EH, Milles J, Webb AG, van Zwet EW, Aartsma-Rus A, Verschuuren JJ & Kan HE Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy. Neuromuscular Disorders 2014 24 4094 16. (https://doi.org/10.1016/j.nmd.2014.01.015)

    • Search Google Scholar
    • Export Citation
  • 12

    Valencia AP, Lai JK, Iyer SR, Mistretta KL, Spangenburg EE, Davis DL, Lovering RM & Gilotra MN Fatty infiltration is a prognostic marker of muscle function After rotator cuff tear. American Journal of Sports Medicine 2018 46 2161216 9. (https://doi.org/10.1177/0363546518769267)

    • Search Google Scholar
    • Export Citation
  • 13

    Carlier PG, Marty B, Scheidegger O, Loureiro de Sousa P, Baudin PY, Snezhko E & Vlodavets D Skeletal muscle quantitative nuclear magnetic resonance imaging and spectroscopy as an outcome measure for clinical trials. Journal of Neuromuscular Diseases 2016 3 128. (https://doi.org/10.3233/JND-160145)

    • Search Google Scholar
    • Export Citation
  • 14

    Noble JJ, Keevil SF, Totman J & Charles-Edwards GD In vitro and in vivo comparison of two-, three- and four-point Dixon techniques for clinical intramuscular fat quantification at 3 T. British Journal of Radiology 2014 87 20130761. (https://doi.org/10.1259/bjr.20130761)

    • Search Google Scholar
    • Export Citation
  • 15

    Díaz-Manera J, Llauger J, Gallardo E & Illa I Muscle MRI in muscular dystrophies. Acta Myologica 2015 34 95108.

  • 16

    Martel-Duguech L, Alonso-Jiménez A, Bascuñana H, Díaz-Manera J, Llauger J, Nuñez-Peralta C, Biagetti B, Montesinos P, Webb SM & Valassi E Thigh muscle fat infiltration is associated with impaired physical performance despite remission in Cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism 2020 105 20392049. (https://doi.org/10.1210/clinem/dgz329)

    • Search Google Scholar
    • Export Citation
  • 17

    Guedes da Silva DP, Guimarães FS, Dias CM, Guimarães Sde A, Kasuki L, Gadelha MR, Camilo GB & Lopes AJ On the functional capacity and quality of life of patients with acromegaly: are they candidates for rehabilitation programs? Journal of Physical Therapy Science 2013 25 14971 501. (https://doi.org/10.1589/jpts.25.1497)

    • Search Google Scholar
    • Export Citation
  • 18

    Homem TS, Guimarães FS, Soares MS, Kasuki L, Gadelha MR & Lopes AJ Balance control and peripheral muscle function in aging: a comparison between individuals with acromegaly and healthy subjects. Journal of Aging and Physical Activity 2017 25 2182 2 7. (https://doi.org/10.1123/japa.2016-0100)

    • Search Google Scholar
    • Export Citation
  • 19

    Haliloglu O, Topsakal N, Camliguney F, Polat Korkmaz O, Sahin S, Cotuk B, Kadioglu P & Erkut O Static and dynamic balances of patients with acromegaly and impact of exercise on balance. Pituitary 2019 22 497506. (https://doi.org/10.1007/s11102-019-00979-3)

    • Search Google Scholar
    • Export Citation
  • 20

    Füchtbauer L, Olsson DS, Bengtsson , Norrman LL, Sunnerhagen KS & Johannsson G Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up. European Journal of Endocrinology 2017 177 2172 2 6. (https://doi.org/10.1530/EJE-17-0120)

    • Search Google Scholar
    • Export Citation
  • 21

    Freda PU, Shen W, Reyes-Vidal CM, Geer EB, Arias-Mendoza F, Gallagher D & Heymsfield SB Skeletal muscle mass in acromegaly assessed by magnetic resonance imaging and dual-photon X-ray absorptiometry. Journal of Clinical Endocrinology and Metabolism 2009 94 2880288 6. (https://doi.org/10.1210/jc.2009-0026)

    • Search Google Scholar
    • Export Citation
  • 22

    Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K & Melmed S A consensus on criteria for cure of acromegaly. Journal of Clinical Endocrinology and Metabolism 2010 95 3141314 8. (https://doi.org/10.1210/jc.2009-2670)

    • Search Google Scholar
    • Export Citation
  • 23

    Alexopoulou O, Bex M, Abs R, T’Sjoen G, Velkeniers B & Maiter D Divergence between growth hormone and insulin-like growth factor-I concentrations in the follow-up of acromegaly. Journal of Clinical Endocrinology and Metabolism 2008 93 132413 30. (https://doi.org/10.1210/jc.2007-2104)

    • Search Google Scholar
    • Export Citation
  • 24

    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS & Montori VM Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2010 95 253625 59. (https://doi.org/10.1210/jc.2009-2354)

    • Search Google Scholar
    • Export Citation
  • 25

    Booth M Assessment of physical activity: an international perspective. Research Quarterly for Exercise and Sport 2000 71 (Supplement 2) 1141 20. (https://doi.org/10.1080/02701367.2000.11082794)

    • Search Google Scholar
    • Export Citation
  • 26

    Bellamy N, Buchanan WW, Goldsmith CH, Campbell J& Stitt LW Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee – PubMed. Journal of Rheumatology 1988 15 183318 40.

    • Search Google Scholar
    • Export Citation
  • 27

    Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y & Sayer AA Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing 2019 48 1631.

    • Search Google Scholar
    • Export Citation
  • 28

    Møller N, Schmitz O, Pørksen N, Møller J & Jørgensen JOL Dose-response studies on the metabolic effects of a growth hormone pulse in humans. Metabolism: Clinical and Experimental 1992 41 17217 5. (https://doi.org/10.1016/0026-0495(9290147-3)

    • Search Google Scholar
    • Export Citation
  • 29

    Krag MB, Gormsen LC, Guo ZK, Christiansen JS, Jensen MD, Nielsen S & Jørgensen JOL Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics. American Journal of Physiology: Endocrinology and Metabolism 2007 292 E920E927. (https://doi.org/10.1152/ajpendo.00374.2006)

    • Search Google Scholar
    • Export Citation
  • 30

    Flores-Morales A, Ståhlberg N, Tollet-Egnell P, Lundeberg J, Malek RL, Quackenbush J, Lee NH & Norstedt G Microarray analysis of the in vivo effects of hypophysectomy and growth hormone treatment on gene expression in the rat. Endocrinology 2001 142 316331 76. (https://doi.org/10.1210/endo.142.7.8235)

    • Search Google Scholar
    • Export Citation
  • 31

    Tollet-Egnell P, Flores-Morales A, Ståhlberg N, Malek RL, Lee N & Norstedt G Gene expression profile of the aging process in rat liver: normalizing effects of growth hormone replacement. Molecular Endocrinology 2001 15 3083 18. (https://doi.org/10.1210/mend.15.2.0594)

    • Search Google Scholar
    • Export Citation
  • 32

    Tollet-Egnell P, Parini P, Ståhlberg N, Lönnstedt I, Lee NH, Rudling M, Flores-Morales A & Norstedt G Growth hormone-mediated alteration of fuel metabolism in the aged rat as determined from transcript profiles. Physiological Genomics 2004 16 26126 7. (https://doi.org/10.1152/physiolgenomics.00093.2002)

    • Search Google Scholar
    • Export Citation
  • 33

    Sjögren K, Leung KC, Kaplan W, Gardiner-Garden M, Gibney J & Ho KKY Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men. American Journal of Physiology: Endocrinology and Metabolism 2007 293 E364E371. (https://doi.org/10.1152/ajpendo.00054.2007)

    • Search Google Scholar
    • Export Citation
  • 34

    Chikani V & Ho KKY Action of GH on skeletal muscle function: molecular and metabolic mechanisms. Journal of Molecular Endocrinology 2014 52 R107R123 (https://doi.org/10.1530/JME-13-0208)

    • Search Google Scholar
    • Export Citation
  • 35

    Bischoff HA, Stähelin HB, Monsch AU, Iversen MD, Weyh A, von Dechend M, Akos R, Conzelmann M, Dick W & Theiler R Identifying a cut-off point for normal mobility: a comparison of the timed ‘up and go’ test in community-dwelling and institutionalised elderly women. Age and Ageing 2003 32 3153 20. (https://doi.org/10.1093/ageing/32.3.315)

    • Search Google Scholar
    • Export Citation
  • 36

    Christopher A, Kraft E, Olenick H, Kiesling R & Doty A The reliability and validity of the timed up and go as a clinical tool in individuals with and without disabilities across a lifespan: a systematic review: psychometric properties of the timed up and go. Disability and Rehabilitation 2019 In press. (https://doi.org/10.1080/09638288.2019.1682066)

    • Search Google Scholar
    • Export Citation
  • 37

    Cuneo RC, Salomon F, Wiles CM & Sönksen PH Skeletal muscle performance in adults with growth hormone deficiency. Hormone Research 1990 33 (Supplement 4) 5560. (https://doi.org/10.1159/000181585)

    • Search Google Scholar
    • Export Citation
  • 38

    Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO & Bier DM Effect of growth hormone and resistance exercise on muscle growth in young men. American Journal of Physiology: Endocrinology and Metabolism 1992 262 26126 7.

    • Search Google Scholar
    • Export Citation
  • 39

    Johannsson G, Grimby G, Sunnerhagen KS & Bengtsson BA Two years of growth hormone (GH) treatment increase isometric and isokinetic muscle strength in GH-deficient adults 1. Journal of Clinical Endocrinology and Metabolism 1997 82 287728 84. (https://doi.org/10.1210/jcem.82.9.4204)

    • Search Google Scholar
    • Export Citation
  • 40

    Chikani V, Cuneo RC, Hickman I & Ho KKY Growth hormone (GH) enhances anaerobic capacity: impact on physical function and quality of life in adults with GH deficiency. Clinical Endocrinology 2016 85 66066 8. (https://doi.org/10.1111/cen.13147)

    • Search Google Scholar
    • Export Citation
  • 41

    Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, Boudreau R, Manini TM, Nevitt M & Newman AB Longitudinal study of muscle strength, quality, and adipose tissue infiltration. American Journal of Clinical Nutrition 2009 90 157915 85. (https://doi.org/10.3945/ajcn.2009.28047)

    • Search Google Scholar
    • Export Citation
  • 42

    Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, Simonsick EM, Tylavsky FA, Visser M & Newman AB The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences 2006 61 105910 64. (https://doi.org/10.1093/gerona/61.10.1059)

    • Search Google Scholar
    • Export Citation
  • 43

    Goodpaster BH, Chomentowski P, Ward BK, Rossi A, Glynn NW, Delmonico MJ, Kritchevsky SB, Pahor M & Newman AB Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. Journal of Applied Physiology 2008 105 14981 503. (https://doi.org/10.1152/japplphysiol.90425.2008)

    • Search Google Scholar
    • Export Citation
  • 44

    Roden M Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes. International Journal of Obesity 2005 29 (Supplement 2) S111S11 5. (https://doi.org/10.1038/sj.ijo.0803102)

    • Search Google Scholar
    • Export Citation
  • 45

    Pellegrinelli V, Rouault C, Rodriguez-Cuenca S, Albert V, Edom-Vovard F, Vidal-Puig A, Clément K, Butler-Browne GS & Lacasa D Human adipocytes induce inflammation and atrophy in muscle cells during obesity. Diabetes 2015 64 31213 13 4. (https://doi.org/10.2337/db14-0796)

    • Search Google Scholar
    • Export Citation
  • 46

    Buck M & Chojkier M Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO Journal 1996 15 175317 65. (https://doi.org/10.1002/j.1460-2075.1996.tb00524.x)

    • Search Google Scholar
    • Export Citation
  • 47

    Baumann CW, Kwak D, Liu HM & Thompson LV Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality? Journal of Applied Physiology 2016 121 104710 52. (https://doi.org/10.1152/japplphysiol.00321.2016)

    • Search Google Scholar
    • Export Citation
  • 48

    Lamounier-Zepter V, Ehrhart-Bornstein M & Bornstein SR Metabolic syndrome and the endocrine stress system. Hormone and Metabolic Research 2006 38 4374 4 1. (https://doi.org/10.1055/s-2006-947837)

    • Search Google Scholar
    • Export Citation
  • 49

    Szendroedi J, Zwettler E, Schmid AI, Chmelik M, Pacini G, Kacerovsky G, Smekal G, Nowotny P, Wagner O & Schnack C Reduced basal ATP synthetic flux of skeletal muscle in patients with previous acromegaly. PLoS ONE 2008 3 e3958. (https://doi.org/10.1371/journal.pone.0003958)

    • Search Google Scholar
    • Export Citation
  • 50

    Yoshida Y, Marcus RL & Lastayo PC Intramuscular adipose tissue and central activation in older adults. Muscle and Nerve 2012 46 813816. (https://doi.org/10.1002/mus.23506)

    • Search Google Scholar
    • Export Citation
  • 51

    Madsen M, Krusenstjerna-Hafstrmø T, Mløler L, Christensen B, Vendelbo MH, Pedersen SB, Frystyk J, Jessen N, Hansen TK & Stdøkilde-Jrøgensen H Fat content in liver and skeletal muscle changes in a reciprocal manner in patients with acromegaly during combination therapy with a somatostatin analog and a GH receptor antagonist: a randomized clinical trial. Journal of Clinical Endocrinology and Metabolism 2012 97 12271235. (https://doi.org/10.1210/jc.2011-2681)

    • Search Google Scholar
    • Export Citation
  • 52

    Neggers SJ, Kopchick JJ, Jørgensen JOL & Van Der Lely AJ Hypothesis: extra-hepatic acromegaly: a new paradigm? European Journal of Endocrinology 2011 164 1116. (https://doi.org/10.1530/EJE-10-0969)

    • Search Google Scholar
    • Export Citation
  • 53

    Abildgaard J, Danielsen ER, Dorph E, Thomsen C, Juul A, Ewertsen C, Pedersen BK, Pedersen AT, Ploug T & Lindegaard B Ectopic lipid deposition is associated With insulin resistance in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 2018 103 33943404. (https://doi.org/10.1210/jc.2018-00554)

    • Search Google Scholar
    • Export Citation