Metabolic Profile and Echocardiographic Evaluation in Adults with Growth Hormone Deficiency

Abstract

Adult growth hormone deficiency (AGHD) is associated with increased cardiovascular risks. The primary endpoint of this retrospective cohort study was to compare metabolic profile and echocardiographic parameters in childhood-onset (CO) and adulthood-onset (AO) AGHD patients. 26 patients with CO AGHD (19 males, 26.8±8.5 years) and 41 patients with AO AGHD (23 males, 35.1±6.8 years) were included. The standard deviation score of insulin-like growth factor-1 (IGF-1 SDS), metabolic profile, liver sonography and echocardiographic parameters were compared. The IGF-1 SDS were significantly lower in CO AGHD patients (p<0.05). AO AGHD patients showed much profound glycolipid aberrations, elevated C-reactive protein levels (p=0.012), and proportionally higher prevalence of non-alcoholic fatty liver disease (95.2% vs.8.3%, p<0.001). In all subjects, IGF-1 SDS was negatively related to low-density lipoprotein cholesterol, and positively related to total cholesterol and lipoprotein a (Lpa). There were significant differences between the two group with regard to the correlations between IGF-1 SDS and high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, LPa, uric acid and creatinine (all p for interaction<0.05). CO AGHD patients exhibited smaller heart, but similar ventricular ejection fraction compared to AO AGHD patients. AGHD may be a group of heterogenous entity based on the onset ages of disease. AO patients had prominent metabolic disorders, while CO patients had smaller heart but similar cardiac performance. Whether growth hormone replacement therapy will equally benefit both CO and AO AGHD patients needs further investigations.

Key words

adult growth hormone deficiency - cardiac function - metabolic profile - childhood-onset - adulthood-onset

^* These authors conrtibuted equally.

Publication History

Received: 01 June 2022

Accepted after revision: 09 September 2022

Article published online:
18 October 2022

• References

• 1 Mariam G, Sally R. Pituitary hypoplasia. Endocrinol Metab Clin North Am 2017; 46: 247-257
• 2 Melmed S. Pathogenesis and diagnosis of growth hormone deficiency in adults. N Engl J Med 2019; 380: 2551-2562
• 3 Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 285-288
• 4 Lombardi G, Di Somma C, Grasso LF. et al. The cardiovascular system in growth hormone excess and growth hormone deficiency. J Endocrinol Inves 2012; 35: 1021-1029
• 5 Svensson J, Bengtsson BA, Rosen T. et al. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab 2004; 89: 3306-3312
• 6 Palmeiro CR, Anand R, Dardi IK. et al. Growth hormone and the cardiovascular system. Cardiol Rev 2012; 20: 197-207
• 7 Annamaria C, Carolina DS, Rosario P. et al. The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J Clin Endocrinol Metab 2002; 87: 1088-1093
• 8 Masahiro M, Hidesuke K, Ishikazu M. et al. A study of carotid intima-media thickness in GH-deficient Japanese adults during onset among adults and children. Eur J Endocrinol 2003; 148: 333-338
• 9 Chikani V, Ho KK. Action of GH on skeletal muscle function: molecular and metabolic mechanisms. J Mol Endocrinol 2013; 52: R107-R123
• 10 Mark RP, Andre PB, Peter JJ. et al. Improvements in body composition after 4 years of growth hormone treatment in adult-onset hypopituitarism compared to age-matched controls. Neuroendocrinology 2019; 109: 131-140
• 11 Yang HB, Zhu HJ, Yan KM. et al. Childhood-onset adult growth hormone D deficiency: clinical, hormonal, and radiological assessment in a single center in China. Horm Res Paediatr 2017; 88: 155-159
• 12 Oliveira JL, Manuel HA, Argemiro DJ. et al. Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults. J Clin Endocrinol Metab 2007; 92: 4664-4670
• 13 Colao A. The GH-IGF-I axis and the cardiovascular system: clinical implications. Clin Endocrinol 2008; 69: 347-358
• 14 Ziagaki A, Blaschke D, Haverkamp W. et al. Long-term growth hormone (GH) replacement of adult GH deficiency (GHD) benefits the heart. Eur J Endocrinol 2019; 181: 79-91
• 15 Attanasio AF, Lamberts SW, Matranga AM. et al. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult growth hormone deficiency study group. J Clin Endocrinol Metab 1997; 82: 82-88
• 16 Molitch ME, Clemmons DR, Malozowski S. et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1587-1609
• 17 Zhu HJ, Xu Y, Gong FY. et al. Reference ranges for serum insulin-like growth factor I (IGF-I) in healthy Chinese adults. PLoS One 2017; 12: e0185561
• 18 Echocardiography group. Chinese medical association, guidelines for echocardiographic measurement in Chinese adults (in Chinese). Chin J Ultrasonogr 2016; 25: 645-666
• 19 Isgaard J, Tivesten A, Friberg P. et al. The GH–IGF-I axis and the cardiovascular system: clinical implications. Clin Endocrinol 2008; 69: 347-358
• 20 Tang JH, Ma LL, Yu TX. et al. Insulin-like growth factor-1 as a prognostic marker in patients with acute ischemic stroke. PLoS One 2014; 9: e99186
• 21 McCallum RW, Petrie JR, Dominiczak AF. et al. Growth hormone deficiency and vascular risk. Clin Endocrinol 2002; 57: 11-24
• 22 Huseyin O, Fatma S, Ali E. et al. Coronary flow reserve is impaired in patients with adult growth hormone (GH) deficiency. Clin Endocrinol (Oxf) 2007; 66: 524-529
• 23 Longobardi S, Cuocolo A, Merola B. et al. Left ventricular function in young adults with childhood and adulthood onset growth hormone deficiency. Clinical Endocr 1998; 48: 137-143
• 24 Raquel SJ, Bernardo L, Caio B. et al. Effects of growth hormone replacement therapy on metabolic and cardiac parameters, in adult patients with childhood-onset growth hormone deficiency. Growth Horm IGF Res 2003; 13: 81-88
• 25 Minczykowski A, Gryczynska M, Ziemnicka K. et al. The influence of growth hormone (GH) therapy on cardiac performance in patients with childhood onset GH deficiency. Growth Horm IGF Res 2005; 15: 156-164
• 26 Andrzej M, MAria G, Katarzyna Z. et al. The influence of growth hormone therapy on ultrasound myocardial tissue characterization in patients with childhood onset GH deficiency. Int J Cardiol 2005; 101: 257-263
• 27 Ajay T, Donatella C, Marcovecchio ML. et al. Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting. J Clin Endocrinol Metab 2014; 99: 2198-2207
• 28 Ren Z, Wang Y, Chen Q. et al. Correlation of significantly decreased serum circulating mesencephalic astrocyte-derived neurotrophic factor level with an increased risk of future cardiovascular disease in adult patients with growth hormone deficiency. Front Endocrinol (Lausanne) 2021; 12: 671126
• 29 Fideleff HL, Boquete H, Stalldecker G. et al. Comparative results of a 4-year study on cardiovascular parameters, lipid metabolism, body composition and bone mass between untreated and treated adult growth hormone deficient patients. Growth Horm IGF Res 2008; 18: 318-324
• 30 Maison P, Balkau B, Souberbielle JC. et al. Evidence for distinct effects of GH and IGF-I in the metabolic syndrome. Diabetic Med 2007; 24: 1012-1018
• 31 Rudling M, Norstedt G, Olivecrona H. et al. Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci U S A 1992; 89: 6983-6987
• 32 Yutaka T. Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver. Endocr J 2012; 59: 955-962
• 33 Nishizawa H, Genzo I, Ayumi M. et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. Eur J Endocrinol 2012; 167: 67-74
• 34 Ichikawa T, Hamasaki K, Ishikawa H. et al. Non-alcoholic steatohepatitis and hepatic steatosis in patients with adult onset growth hormone deficiency. Gut 2003; 52: 914
• 35 Chris JG, Andrew JI, Christina D. et al. Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study. Eur J Endocrinol 2012; 166: 993-1002
• 36 Malin CE, Lovisa L, David NÅ. et al. Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis. BMC Med 2019; 17: 141-151