Increased number of retinal vessels in acromegaly

in European Journal of Endocrinology

Correspondence should be addressed to L Füchtbauer; Email: laila.fuchtbauer@vgregion.se
Restricted access

Objective

Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes.

Design

Two independent observational studies, one being prospective and the other retrospective and cross-sectional.

Methods

Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology.

Results

Patients with acromegaly had a median (interquartile range) of 34.3 (30.0–39.0) vessel branching points compared to 27.0 (24.0–29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points (34.2 (32.5–35.6)), but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly.

Conclusions

Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 143 143 143
Full Text Views 19 19 19
PDF Downloads 11 11 11
  • 1

    EspositoDRagnarssonOGranfeldtDMarlowTJohannssonGOlssonDS. Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study. European Journal of Endocrinology 2018 459469. (https://doi.org/10.1530/EJE-18-0015)

    • Search Google Scholar
    • Export Citation
  • 2

    HoldawayIMBollandMJGambleGD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. European Journal of Endocrinology 2008 8995. (https://doi.org/10.1530/EJE-08-0267)

    • Search Google Scholar
    • Export Citation
  • 3

    MollerNJorgensenJOAbildgardNOrskovLSchmitzOChristiansenJS. Effects of growth hormone on glucose metabolism. Hormone Research 1991 (Supplement 1) 3235. (https://doi.org/10.1159/000182185)

    • Search Google Scholar
    • Export Citation
  • 4

    LesenEGranfeldtDHouchardADinetJBerthonAOlssonDSBjorholtIJohannssonG. Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study. European Journal of Endocrinology 2017 203212. (https://doi.org/10.1530/EJE-16-0623)

    • Search Google Scholar
    • Export Citation
  • 5

    IkramMKCheungCYLorenziMKleinRJonesTLWongTY & NIH/JDRF Workshop on Retinal Biomarker for Diabetes Group. Retinal vascular caliber as a biomarker for diabetes microvascular complications. Diabetes Care 2013 750759. (https://doi.org/10.2337/dc12-1554)

    • Search Google Scholar
    • Export Citation
  • 6

    BereketALangCHWilsonTA. Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Hormone and Metabolic Research 1999 172181. (https://doi.org/10.1055/s-2007-978716)

    • Search Google Scholar
    • Export Citation
  • 7

    JehlePMJehleDRMohanSBohmBO. Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and type 2 diabetes mellitus patients. Journal of Endocrinology 1998 297306. (https://doi.org/10.1677/joe.0.1590297)

    • Search Google Scholar
    • Export Citation
  • 8

    LewittMSDentMSHallK. The insulin-like growth factor system in obesity, insulin resistance and type 2 diabetes mellitus. Journal of Clinical Medicine 2014 15611574. (https://doi.org/10.3390/jcm3041561)

    • Search Google Scholar
    • Export Citation
  • 9

    PayneJFTangprichaVClevelandJLynnMJRayRSrivastavaSK. Serum insulin-like growth factor-I in diabetic retinopathy. Molecular Vision 2011 23182324.

    • Search Google Scholar
    • Export Citation
  • 10

    DillsDGMossSEKleinRKleinBE. Association of elevated IGF-I levels with increased retinopathy in late-onset diabetes. Diabetes 1991 17251730. (https://doi.org/10.2337/diab.40.12.1725)

    • Search Google Scholar
    • Export Citation
  • 11

    FrystykJ. The growth hormone hypothesis – 2005 revision. Hormone and Metabolic Research 2005 (Supplement 1) 4448. (https://doi.org/10.1055/s-2005-861362)

    • Search Google Scholar
    • Export Citation
  • 12

    PoulsenJE. Recovery from retinopathy in a case of diabetes with Simmonds’ disease. Diabetes 1953 712. (https://doi.org/10.2337/diab.2.1.7)

    • Search Google Scholar
    • Export Citation
  • 13

    TeuscherAEscherFKonigHZahndG. Long-term effects of transsphenoidal hypophysectomy on growth hormone, renal function and eyeground in patients with diabetic retinopathy. Diabetes 1970 502518. (https://doi.org/10.2337/diab.19.7.502)

    • Search Google Scholar
    • Export Citation
  • 14

    BallintineEJFoxmanSGordenPRothJ. Rarity of diabetic retinopathy in patients with acromegaly. Archives of Internal Medicine 1981 16251627.

    • Search Google Scholar
    • Export Citation
  • 15

    AmemiyaTToibanaMHashimotoMOsekoFImuraH. Diabetic retinopathy in acromegaly. Ophthalmologica 1978 7480. (https://doi.org/10.1159/000308696)

    • Search Google Scholar
    • Export Citation
  • 16

    AzzougSChentliF. Diabetic retinopathy in acromegaly. Indian Journal of Endocrinology and Metabolism 2014 407409. (https://doi.org/10.4103/2230-8210.131207)

    • Search Google Scholar
    • Export Citation
  • 17

    RimmerSKeatingCChouTFarbMDChristensonPDFoosRYBatemanJB. Growth of the human optic disk and nerve during gestation, childhood, and early adulthood. American Journal of Ophthalmology 1993 748753. (https://doi.org/10.1016/s0002-9394(14)73476-2)

    • Search Google Scholar
    • Export Citation
  • 18

    HellstromASvenssonE. Optic disc size and retinal vessel characteristics in healthy children. Acta Ophthalmologica Scandinavica 1998 260267. (https://doi.org/10.1034/j.1600-0420.1998.760302.x)

    • Search Google Scholar
    • Export Citation
  • 19

    The Swedish National Diabetes Register. Ett knapptryck för förbättringsarbete 2019, Mar 9. (available at: https://www.ndr.nu/#/knappen)

    • Search Google Scholar
    • Export Citation
  • 20

    ElmlingerMWKuhnelWWeberMMRankeMB. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3). Clinical Chemistry and Laboratory Medicine 2004 654664. (https://doi.org/10.1515/CCLM.2004.112)

    • Search Google Scholar
    • Export Citation
  • 21

    BidlingmaierMFriedrichNEmenyRTSprangerJWolthersODRoswallJKornerAObermayer-PietschBHubenerCDahlgrenJ et al. Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. Journal of Clinical Endocrinology and Metabolism 2014 17121721. (https://doi.org/10.1210/jc.2013-3059)

    • Search Google Scholar
    • Export Citation
  • 22

    StromlandKHellstromAGustavssonT. Morphometry of the optic nerve and retinal vessels in children by computer-assisted image analysis of fundus photographs. Graefe’s Archive for Clinical and Experimental Ophthalmology 1995 150153. (https://doi.org/10.1007/bf00166607)

    • Search Google Scholar
    • Export Citation
  • 23

    WalshJB. Hypertensive retinopathy. Description, classification, and prognosis. Ophthalmology 1982 11271131. (https://doi.org/10.1016/S0161-6420(82)34664-3)

    • Search Google Scholar
    • Export Citation
  • 24

    SchiavonFMaffeiPMartiniCDe CarloEFaisCTodescoSSicoloN. Morphologic study of microcirculation in acromegaly by capillaroscopy. Journal of Clinical Endocrinology and Metabolism 1999 31513155. (https://doi.org/10.1210/jcem.84.9.5952)

    • Search Google Scholar
    • Export Citation
  • 25

    LambovaSNMuller-LadnerU. The specificity of capillaroscopic pattern in connective autoimmune diseases. A comparison with microvascular changes in diseases of social importance: arterial hypertension and diabetes mellitus. Modern Rheumatology 2009 600605. (https://doi.org/10.1007/s10165-009-0221-x)

    • Search Google Scholar
    • Export Citation
  • 26

    OomenPHBeentjesJABosmaESmitAJReitsmaWDDullaartRP. Reduced capillary permeability and capillary density in the skin of GH-deficient adults: improvement after 12 months GH replacement. Clinical Endocrinology 2002 519524. (https://doi.org/10.1046/j.1365-2265.2002.01517.x)

    • Search Google Scholar
    • Export Citation
  • 27

    HanaVPraznyMMarekJSkrhaJJustovaV. Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement. European Journal of Endocrinology 2002 333337. (https://doi.org/10.1530/eje.0.1470333)

    • Search Google Scholar
    • Export Citation
  • 28

    HellstromASvenssonECarlssonBNiklassonAAlbertsson-WiklandK. Reduced retinal vascularization in children with growth hormone deficiency. Journal of Clinical Endocrinology and Metabolism 1999 795798. (https://doi.org/10.1210/jcem.84.2.5484)

    • Search Google Scholar
    • Export Citation
  • 29

    HellstromACarlssonBNiklassonASegnestamKBoguszewskiMde LacerdaLSavageMSvenssonESmithLWeinbergerD et al. IGF-I is critical for normal vascularization of the human retina. Journal of Clinical Endocrinology and Metabolism 2002 34133416. (https://doi.org/10.1210/jcem.87.7.8629)

    • Search Google Scholar
    • Export Citation
  • 30

    Pereira-GurgelVMFaroACSalvatoriRChagasTACarvalho-JuniorJFOliveiraCRCostaUMMeloGBHellstromAAguiar-OliveiraMH. Abnormal vascular and neural retinal morphology in congenital lifetime isolated growth hormone deficiency. Growth Hormone and IGF Research 2016 1115. (https://doi.org/10.1016/j.ghir.2016.07.001)

    • Search Google Scholar
    • Export Citation
  • 31

    BlankDRiedlMReitnerASchnackCSchernthanerGClodiMFrischHLugerA. Growth hormone replacement therapy is not associated with retinal changes. Journal of Clinical Endocrinology and Metabolism 2000 634636. (https://doi.org/10.1210/jcem.85.2.6403)

    • Search Google Scholar
    • Export Citation
  • 32

    BogazziFManettiLBartalenaLGasperiMGrassoLCecconiERagoTPincheraAMartinoE. Thyroid vascularity is increased in patients with active acromegaly. Clinical Endocrinology 2002 6570. (https://doi.org/10.1046/j.1365-2265.2002.01562.x)

    • Search Google Scholar
    • Export Citation
  • 33

    LieglRLofqvistCHellstromASmithLE. IGF-1 in retinopathy of prematurity, a CNS neurovascular disease. Early Human Development 2016 1319. (https://doi.org/10.1016/j.earlhumdev.2016.09.008)

    • Search Google Scholar
    • Export Citation
  • 34

    Messias de LimaCFDos Santos ReisMDda Silva RamosFWAyres-MartinsSSmaniottoS. Growth hormone modulates in vitro endothelial cell migration and formation of capillary-like structures. Cell Biology International 2017 577584. (https://doi.org/10.1002/cbin.10747)

    • Search Google Scholar
    • Export Citation
  • 35

    SonntagWELynchCDCooneyPTHutchinsPM. Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology 1997 35153520. (https://doi.org/10.1210/endo.138.8.5330)

    • Search Google Scholar
    • Export Citation
  • 36

    KhanASLynchCDSaneDCWillinghamMCSonntagWE. Growth hormone increases regional coronary blood flow and capillary density in aged rats. Journals of Gerontology: Series A Biological Sciences and Medical Sciences 2001 B364B371. (https://doi.org/10.1093/gerona/56.8.b364)

    • Search Google Scholar
    • Export Citation
  • 37

    TucciMNygardKTanswellBVFarberHWHillDJHanVK. Modulation of insulin-like growth factor (IGF) and IGF binding protein biosynthesis by hypoxia in cultured vascular endothelial cells. Journal of Endocrinology 1998 1324. (https://doi.org/10.1677/joe.0.1570013)

    • Search Google Scholar
    • Export Citation
  • 38

    ShigematsuSYamauchiKNakajimaKIijimaSAizawaTHashizumeK. IGF-1 regulates migration and angiogenesis of human endothelial cells. Endocrine Journal 1999 (Supplement) S59S62. (https://doi.org/10.1507/endocrj.46.suppl_s59)

    • Search Google Scholar
    • Export Citation
  • 39

    SmithLEShenWPerruzziCSokerSKinoseFXuXRobinsonGDriverSBischoffJZhangB et al. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nature Medicine 1999 13901395. (https://doi.org/10.1038/70963)

    • Search Google Scholar
    • Export Citation
  • 40

    MieleCRochfordJJFilippaNGiorgetti-PeraldiSVan ObberghenE. Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways. Journal of Biological Chemistry 2000 2169521702. (https://doi.org/10.1074/jbc.M000805200)

    • Search Google Scholar
    • Export Citation
  • 41

    SilhaJVKrsekMHanaVMarekJWeissVJezkovaJRosickaMJarkovskaZMurphyLJ. The effects of growth hormone status on circulating levels of vascular growth factors. Clinical Endocrinology 2005 7986. (https://doi.org/10.1111/j.1365-2265.2005.02303.x)

    • Search Google Scholar
    • Export Citation
  • 42

    YuDCaiYZhouWShengJXuZ. The potential of angiogenin as a serum biomarker for diseases: systematic review and meta-analysis. Disease Markers 2018 1984718. (https://doi.org/10.1155/2018/1984718)

    • Search Google Scholar
    • Export Citation
  • 43

    Wilkinson-BerkaJLWraightCWertherG. The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. Current Medicinal Chemistry 2006 33073317. (https://doi.org/10.2174/092986706778773086)

    • Search Google Scholar
    • Export Citation
  • 44

    Growth Hormone Antagonist for Proliferative Diabetic Retinopathy Study Group. The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology 2001 22662272. (https://doi.org/10.1016/s0161-6420(01)00853-3)

    • Search Google Scholar
    • Export Citation
  • 45

    van HerptTTWLemmersRFHvan HoekMLangendonkJGErdtsieckRJBravenboerBLucasAMulderMTHaakHRLieverseAG et al. Introduction of the DiaGene study: clinical characteristics, pathophysiology and determinants of vascular complications of type 2 diabetes. Diabetology and Metabolic Syndrome 2017 47. (https://doi.org/10.1186/s13098-017-0245-x)

    • Search Google Scholar
    • Export Citation
  • 46

    WuTEChenHS. Increased prevalence of proliferative retinopathy in patients with acromegaly. Journal of the Chinese Medical Association 2018 230235. (https://doi.org/10.1016/j.jcma.2017.09.013)

    • Search Google Scholar
    • Export Citation
  • 47

    SongJChenSLiuXDuanHKongJLiZ. Relationship between C-reactive protein level and diabetic retinopathy: a systematic review and meta-analysis. PLoS ONE 2015 e0144406. (https://doi.org/10.1371/journal.pone.0144406)

    • Search Google Scholar
    • Export Citation
  • 48

    AndreassenMVestergaardHKristensen. Concentrations of the acute phase reactants high-sensitive C-reactive protein and YKL-40 and of interleukin-6 before and after treatment in patients with acromegaly and growth hormone deficiency. Clinical Endocrinology 2007 909916. (https://doi.org/10.1111/j.1365-2265.2007.02986.x)

    • Search Google Scholar
    • Export Citation