Cardiovascular outcomes and conventional risk factors in non-diabetic adult patients with GH deficiency: A long-term retrospective cohort study

Published:November 05, 2015DOI:


      • Increased cardiovascular (CV) risk has been reported in patients with GH deficiency.
      • The role for conventional CV risk factors has not been well established.
      • We investigated the association among the main CV risk factors and outcomes.
      • We confirm this association being as important as in the general population.
      • Treatment of GHD patients should be inclusive of CV risk factors.



      To investigate the association between cardiovascular (CV) risk factors and cumulative CV events in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT).


      53 non-diabetic adult GHD patients, aged 45.4 ± 14.3 years, 31 females, with a median follow up of 140 months, were divided into two groups based on the presence (group A) or absence (group B) of systemic hypertension. Tertiles of age and LDL-cholesterol were considered as further potential prognosticators. Cumulative CV event rates were recorded and analyzed by Kaplan–Mayer method. Differences between patients with and without events were also evaluated.


      Seventeen patients (32%) entered the group A and 36 (68%) the group B. A composite of fatal and non-fatal CV events occurred in 22.6% of patients, 47.1% in group A and 11% in group B (p = 0.01), CV deaths in 3 patients (5.7%; annual death rate 0.49%), 2 of whom were in group A. At Kaplan–Mayer analysis, hypertension and age > 55 years were major prognosticators. The odds ratio was 7.1 (95% CI: 1.74–29.12, p < 0.003) and 6.2 (95% CI: 1.54–25.04, p < 0.006), respectively. LDL-cholesterol showed borderline statistical significance. Patients with CV events also had high prevalence of left ventricular hypertrophy, left atrial enlargement and subclinical systolic dysfunction.


      In this study, outcomes were mainly related to hypertension and age (partially to LDL-cholesterol), confirming that management of GHD patients must be inclusive of treatment of conventional risk factors, being as important as GHRT. Optimal blood pressure control is crucial when a target organ damage is present and in patients older than 55 years.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Beshah S.A.
        • Johnston D.
        Cardiovascular disease and risk factors in adults with hypopituitarism.
        Clin Endocrinol. 1999; 50: 1-15
        • Tomlinson J.W.
        • Holden N.
        • Hills R.K.
        • Wheatley K.
        • Clayton R.N.
        • Bates A.S.
        • et al.
        Association between premature mortality and hypopituitarism. West Midland Prospective Hypopituitarism Group.
        Lancet. 2001; 357: 425-431
        • Abdu T.A.
        • Neary R.
        • Elhadd T.A.
        • Akber M.
        • Clayton R.N.
        Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities.
        Clin Endocrinol. 2001; 55: 209-216
        • Abs R.
        • Feldt-Rasmussen U.
        • Mattsson A.F.
        • Monson J.P.
        • Bengtsson B.A.
        • Góth M.I.
        • et al.
        Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults. A KIMS database analysis.
        Eur J Endocrinol. 2006; 155: 79-90
        • Sanmarti A.
        • Lucas A.
        • Hawkins F.
        • Webb S.M.
        • Ulied A.
        Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socioeconomic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group.
        Eur J Endocrinol. 1999; 141: 481-489
        • Rosen T.
        • Eden S.
        • Larson G.
        • Wilhelmsen L.
        • Bengtsson B.A.
        Cardiovascular risk factors in adult patients with growth hormone deficiency.
        Acta Endocrinol. 1993; 129: 195-200
        • Colao A.
        The GH–IGF-I axis and the cardiovascular system: clinical implications.
        Clin Endocrinol. 2008; 69: 347-358
        • Cannavò S.
        • Marini F.
        • Curtò L.
        • Torre M.L.
        • de Gregorio C.
        • Salamone I.
        • et al.
        High prevalence of coronary calcifications and increased risk for coronary heart disease in adults with growth hormone deficiency.
        J Endocrinol Invest. 2011; 34: 32-37
        • Van Bunderen C.C.
        • Van Nieuwpoort I.C.
        • Arwert L.I.
        • Heymans M.W.
        • Franken A.A.
        • Koppeschaar H.P.
        • et al.
        Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch National Registry of growth hormone treatment in adults.
        J Clin Endocrinol Metab. 2011; 96: 3151-3159
        • Erfurth E.M.
        • Siesjo P.
        • Bjork-Eriksson T.
        Pituitary disease mortality: is it fiction?.
        Pituitary. 2013; 16: 402-412
        • de Gregorio C.
        • Curtò L.
        • Marini F.
        • Andò G.
        • Trio O.
        • Trimarchi F.
        • et al.
        Hypertension counteracts potential benefits of GH replacement therapy on left ventricular remodeling in adults with growth hormone deficiency.
        J Endocrinol Invest. 2013; 36: 243-248
        • Gabellieri E.
        • Chiovato L.
        • Lage M.
        • Castro A.I.
        • Casanueva F.F.
        Testing growth hormone deficiency in adults.
        Front Horm Res. 2010; 38: 139-144
        • O' Brien E.
        • Asmar R.
        • Beilin L.
        • Imai Y.
        • Mallion J.M.
        • Mancia G.
        • et al.
        European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement.
        J Hypertens. 2003; 21: 821-848
        • Mancia G.
        • Fagard R.
        • Narkiewicz K.
        • Redon J.
        • Zanchetti A.
        • Böhm M.
        • et al.
        ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
        Eur Heart J. 2013; 34: 2159-2219
        • Lang R.M.
        • Bierig M.
        • Devereux R.B.
        • Flachskampf F.A.
        • Foster E.
        • Pellikka P.A.
        • et al.
        Recommendations for chamber quantification.
        Eur J Echocardiogr. 2006; 7: 179-198
        • de Simone G.
        • Devereux R.B.
        • Roman M.J.
        • Ganau A.
        • Saba P.S.
        • Alderman M.H.
        • et al.
        Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension.
        J Am Coll Cardiol. 1994; 23: 1444-1451
        • Verhelst J.
        • Abs R.
        Cardiovascular risk factors in hypopituitary GH-deficient adults.
        Eur J Endocrinol. 2009; 161: S41-S49
        • Gazzaruso C.
        • Gola M.
        • Karamouzis I.
        • Giubbini R.
        • Giustina A.
        Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH—an update.
        J Clin Endocrinol Metab. 2014; 99: 18-29
        • Nielsen E.H.
        • Lindholm J.
        • Laurberg P.
        Excess mortality in women with pituitary disease: a meta-analysis.
        Clin Endocrinol (Oxf). 2007; 67: 693-697
        • Carel J.C.
        • Ecosse E.
        • Landier F.
        • Meguellati-Hakkas D.
        • Kaguelidou F.
        • Rey G.
        • et al.
        Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood Short stature: preliminary report of the French SAGhE study.
        J Clin Endocrinol Metab. 2012; 97: 416-425
        • Gola M.
        • Giustina A.
        Growth hormone deficiency and cardiovascular risk: do we need additional markers?.
        Endocrine. 2012; 42: 240-242
        • Svensson J.
        • Bengtsson B.
        Safety aspects of GH replacement.
        Eur J Endocrinol. 2009; 161: S65-S74
        • Isgaard J.
        • Arcopinto M.
        • Karason K.
        • Cittadini A.
        GH and the cardiovascular system: an update on a topic at heart.
        Endocrine. 2015; 48: 25-35
        • Franklin S.S.
        • Wong N.D.
        Hypertension and cardiovascular disease: contributions of the Framingham Heart Study.
        Glob Heart. 2013; 8: 49-57
        • Boschetti M.
        • Casu M.
        • Moretti S.
        • et al.
        Autonomic nervous system and cardiovascular risk assessment during one year of growth hormone replacement therapy in adults with growth hormone deficiency.
        Hormones. 2015; 14: 134-141
        • Cittadini A.
        • Cuocolo A.
        • Merla B.
        • Fazio S.
        • Sabatini D.
        • Nicolai E.
        • et al.
        Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement.
        Am J Physiol. 1994; 267: E219-E225
        • de Gregorio C.
        • Curtò L.
        • Recupero A.
        • Grimaldi P.
        • Almoto B.
        • Venturino M.
        • et al.
        Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case–control study.
        BMC Endocr Disord. 2006; 6: 1
        • Shimuzu G.
        • Hirota Y.
        • Kita Y.
        • Kawamura K.
        • Saito T.
        • Gaasch W.H.
        Left ventricular midwall mechanics in systemic arterial hypertension: myocardial function is depressed in pressure-overload hypertrophy.
        Circulation. 1991; 83: 1676-1684
        • Cho G.Y.
        • Jeong I.K.
        • Kim S.H.
        • Kim M.K.
        • Park W.J.
        • Oh D.J.
        • et al.
        Effect of growth hormone on cardiac contractility in patients with adult onset growth hormone deficiency.
        Am J Cardiol. 2007; 100: 1035-1039
        • Filipsson Nyström H.
        • Feldt-Rasmussen U.
        • Kourides I.
        • Popovic V.
        • Koltowska-Häggström M.
        • Jonsson B.
        • et al.
        The metabolic consequences of thyroxine replacement in adult hypopituitary patients.
        Pituitary. 2012; 15: 495-504
        • Klose M.
        • Marina D.
        • Hartoft-Nielsen M.L.
        • Klefter O.
        • Gavan V.
        • Hilsted L.
        • et al.
        Central hypothyroidism and its replacement have a significant influence on cardiovascular risk factors in adult hypopituitary patients.
        J Clin Endocrinol Metab. 2013; 98: 3802-3810
        • Filipsson H.
        • Monson J.P.
        • Koltowska-Häggström M.
        • Mattsson A.
        • Johannsson G.
        The impact of glucocorticoid replacement regimens on metabolic outcome and co-morbidity in hypopituitary patients.
        J Clin Endocrinol Metab. 2006; 91: 3954-3961
        • Tomlinson J.W.
        • Holden N.
        • Hills R.K.
        • Wheatley K.
        • Clayton R.N.
        • Bates A.S.
        • et al.
        Association between premature mortality and hypopituitarism.
        Lancet. 2001; 357: 425-431
        • Elbornsson M.
        • Götherström G.
        • Bengtsson B.A.
        • Johannsson G.
        • Svensson J.
        Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation.
        Growth Horm IGF Res. 2013; 23: 249-255