Cardiovascular Risk Factors in Acromegaly: What's the Impact of Disease Control?

Ana Amado; Fernando Araújo; Davide Carvalho

doi:10.1055/s-0043-124668

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2018; 126(08): 505-512
DOI: 10.1055/s-0043-124668

Article

Cardiovascular Risk Factors in Acromegaly: What's the Impact of Disease Control?

Ana Amado

¹Faculty of Medicine University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

,

Fernando Araújo

²Department of Imunohemotherapy, Centro Hospitalar São João, Faculty of Medicine University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

,

Davide Carvalho

³Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Faculty of Medicine University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

› Author Affiliations

Abstract

Objective Cardiovascular disease is one of the most important causes of death in acromegalic patients. The aim of this study is to compare the prevalence of cardiovascular risk factors among acromegalic patients and to evaluate the impact of disease control on these factors.

Material and Methods 11 acromegalic patients with active disease and 12 controlled patients were evaluated for blood pressure, body mass index, glucose, coagulation status, and lipid profile. A group of 11 patients with non-functioning pituitary adenomas was used as control population.

Results Significant differences were found in lipid profile, glucose and coagulation status in both active and controlled patients. Higher levels of fasting glucose (151.2±102.5 mg/dL, p=0.05 and 108.3±23.4 mg/dL, p=0.02 for active and controlled patients respectively) and fibrinogen (427.1±61.9 mg/dL, p=0.02 and 437.3±106.6 mg/dL, p=0.04 for active and controlled patients respectively) were present in both acromegalic groups. Active patients had higher levels of antithrombin III (1.1±0.1 U/mL, p=0.005) and the controlled ones had higher levels of high density lipoprotein cholesterol (56.1±12.5 mg/dL, p=0.05), compared with the non-functioning group. The differences between active and controlled acromegalic patients are that the latter have reduced total cholesterol (170.4±31.7 vs 201.7±34.6 mg/dL, p=0.02), lower density lipoprotein cholesterol (96,8±25,2 vs 130.8±31.5 mg/dL, p=0.01) and antithrombin III (1.0±0.2 vs 1.1±0.1 U/mL, p=0.05).

Conclusion There is some reduction in cardiovascular risk factors with control of the disease, but possibly without the return to basal levels.

Key words

Pituitary adenoma - Cardiovascular risk management - GH

Full Text

References

References
1 Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary 1999; 229-241
2 Katznelson L, Laws Jr. ER, Melmed S. et al. Acromegaly: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology and metabolism 2014; 99: 3933-3951
3 Pivonello R, Auriemma RS, Grasso LF. et al. Complications of acromegaly: Cardiovascular, respiratory and metabolic comorbidities. Pituitary 2017; 20: 46-62
4 Mosca S, Paolillo S, Colao A. et al. Cardiovascular involvement in patients affected by acromegaly: An appraisal. Int J Cardiol 2013; 167: 1712-1718
5 Sacca L, Napoli R, Cittadini A. Growth hormone, acromegaly, and heart failure: An intricate triangulation. Clinical Endocrinology 2003; 59: 660-671
6 Colao A, Marzullo P, Di Somma C. et al. Growth hormone and the heart. Clinical Endocrinology 2001; 54: 137-154
7 Mestron A, Webb SM, Astorga R. et al. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). European journal of endocrinology / European Federation of Endocrine Societies 2004; 151: 439-446
8 Bondanelli M, Ambrosio MR, degli Uberti EC. Pathogenesis and prevalence of hypertension in acromegaly. Pituitary 2001; 4: 239-249
9 Vitale G, Pivonello R, Auriemma RS. et al. Hypertension in acromegaly and in the normal population: Prevalence and determinants. Clinical Endocrinology 2005; 63: 470-476
10 Fedrizzi D, Rodrigues TC, Costenaro F. et al. Hypertension-related factors in patients with active and inactive acromegaly. Arquivos Brasileiros de Endocrinologia e Metabologia 2011; 55: 468-474
11 Minniti G, Moroni C, Jaffrain-Rea ML. et al. Prevalence of hypertension in acromegalic patients: Clinical measurement versus 24-hour ambulatory blood pressure monitoring. Clinical Endocrinology 1998; 48: 149-152
12 Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. The Journal of Clinical Endocrinology and Metabolism 2004; 89: 667-674
13 Wen-Ko C, Szu-Tah C, Feng-Hsuan L. et al. The impact of diabetes mellitus on the survival of patients with acromegaly. Endokrynol Pol 2016; 67: 501-506
14 Fieffe S, Morange I, Petrossians P. et al. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. European Journal of Endocrinology / European Federation of Endocrine Societies 2011; 164: 877-884
15 Jaffrain-Rea ML, Moroni C, Baldelli R. et al. Relationship between blood pressure and glucose tolerance in acromegaly. Clinical Endocrinology 2001; 54: 189-195
16 Tan KC, Shiu SW, Janus ED. et al. LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I. Atherosclerosis 1997; 129: 59-65
17 Twickler TB, Dallinga-Thie GM, Zelissen PM. et al. The atherogenic plasma remnant-like particle cholesterol concentration is increased in the fasting and postprandial state in active acromegalic patients. Clinical Endocrinology 2001; 55: 69-75
18 Beentjes JA, van Tol A, Sluiter WJ. et al. Low plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins. Atherosclerosis 2000; 153: 491-498
19 Arosio M, Sartore G, Rossi CM. et al. LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients. Effects of octreotide therapy. Italian Multicenter Octreotide Study Group. Atherosclerosis 2000; 151: 551-557
20 Freda PU, Shen W, Heymsfield SB. et al. 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. J Clin Endocr Metab 2008; 93: 2334-2343
21 Katznelson L. Alterations in body composition in acromegaly. Pituitary 2009; 12: 136-142
22 Colak A, Yilmaz H, Temel Y. et al. Coagulation parameters and platelet function analysis in patients with acromegaly. J Endocrinol Invest 2016; 39: 97-101
23 Kaluzny M, Bolanowski M, Daroszewski J. et al. The role of fibrinogen and CRP in cardiovascular risk in patients with acromegaly. Endokrynol Pol 2010; 61: 83-88
24 Potter BJ, Beauregard C, Serri O. Serum markers of cardiovascular risk in patients with acromegaly before and after six months of treatment with octreotide LAR. Pituitary 2008; 11: 49-53
25 Erem C, Nuhoglu I, Kocak M. et al. Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI. Endocrine 2008; 33: 270-276
26 Delaroudis SP, Efstathiadou ZA, Koukoulis GN. et al. Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly. Clinical Endocrinology 2008; 69: 279-284
27 Landin-Wilhelmsen K, Tengborn L, Wilhelmsen L. et al. Elevated fibrinogen levels decrease following treatment of acromegaly. Clinical Endocrinology 1997; 46: 69-74
28 Sesmilo G, Fairfield WP, Katznelson L. et al. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocr Metab 2002; 87: 1692-1699
29 Colao A, Auriemma RS, Galdiero M. et al. Effects of initial therapy for five years with somatostatin analogs for acromegaly on growth hormone and insulin-like growth factor-I levels, tumor shrinkage, and cardiovascular disease: a prospective study. The Journal of Clinical Endocrinology and Metabolism 2009; 94: 3746-3756
30 Damjanovic SS, Neskovic AN, Petakov MS. et al. Clinical indicators of biochemical remission in acromegaly: does incomplete disease control always mean therapeutic failure?. Clinical Endocrinology 2005; 62: 410-417
31 Minniti G, Moroni C, Jaffrain-Rea ML. et al. Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients. Clinical Endocrinology 2001; 55: 307-313
32 Jaffrain-Rea ML, Minniti G, Moroni C. et al. Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly. European journal of endocrinology/European Federation of Endocrine Societies 2003; 148: 193-201
33 Couture E, Bongard V, Maiza JC. et al. Glucose status in patients with acromegaly receiving primary treatment with the somatostatin analog lanreotide. Pituitary 2012; 15: 518-525
34 Schutte AE, Volpe M, Tocci G. et al. Revisiting the relationship between blood pressure and insulin-like growth factor-1. Hypertension. 2014; 63: 1070-1077
35 Dimopoulou C, Sievers C, Wittchen HU. et al. Adverse anthropometric risk profile in biochemically controlled acromegalic patients: Comparison with an age- and gender-matched primary care population. Pituitary 2010; 13: 207-214
36 Boero L, Manavela M, Gomez Rosso L. et al. Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly. Clinical Endocrinology 2009; 70: 88-95
37 Maldonado Castro GF, Escobar-Morreale HF, Ortega H. et al. Effects of normalization of GH hypersecretion on lipoprotein(a) and other lipoprotein serum levels in acromegaly. Clinical Endocrinology 2000; 53: 313-319
38 Lin E, Wexler TL, Nachtigall L. et al. Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly. Clinical Endocrinology 2012; 77: 430-438
39 Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Brazilian journal of medical and biological research=Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al.] 2001; 34: 1429-1433
40 Kinoshita Y, Fujii H, Takeshita A. et al. Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic {beta}-cell function is preserved. European Journal of Endocrinology / European Federation of Endocrine Societies 2011; 164: 467-473
41 Urbani C, Sardella C, Calevro A. et al. Effects of medical therapies for acromegaly on glucose metabolism. European Journal of Endocrinology / European Federation of Endocrine Societies 2013; 169: 99-108
42 Cheng S, Al-Agha R, Araujo PB. et al. Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly. PloS One 2013; 8: e73543
43 Reyes-Vidal C, Fernandez JC, Bruce JN. et al. Prospective study of surgical treatment of acromegaly: Effects on ghrelin, weight, adiposity, and markers of CV risk. The Journal of Clinical Endocrinology and Metabolism 2014; 99: 4124-4132
44 Maison P, Balkau B, Souberbielle JC. et al. Evidence for distinct effects of GH and IGF-I in the metabolic syndrome. Diabetic medicine: a journal of the British Diabetic Association 2007; 24: 1012-1018
45 Parkinson C, Drake WM, Wieringa G. et al. Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly. Clinical Endocrinology 2002; 56: 303-311