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Minimizing Cardiometabolic Risk Factors in Patients with Acromegaly

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Pituitary Disorders throughout the Life Cycle

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Abstract

Acromegaly is a rare disease, characterized by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels. It is usually caused by a somatotroph adenoma of the pituitary gland secreting GH. The disease is associated with increased morbidity and mortality, particularly when GH levels remain persistently elevated. Cancer is now the leading cause of death in these patients, but cardiovascular disease remains an important cause of mortality.

In addition to stimulating somatic growth and longitudinal growth of the long bones, patients with acromegaly have been found to have increased prevalence of hypertension, mean systolic and diastolic blood pressure, history of diabetes mellitus and glycosylated hemoglobin, and decreased high-density lipoprotein in addition to having a higher Framingham risk score compared with age- and gender-matched controls of the general population. This leads to increased morbidity and mortality when compared to the general population due to higher cardiovascular risk and a worse metabolic profile believed to be mediated by IGF-1. Increased GH and IGF-1 can also directly cause cardiovascular toxicity.

In this chapter, we discuss how management of acromegaly, with the goal of normalizing IGF-1 as well as treatment of hypopituitarism, can have a potential impact on mitigating the risk of cardiovascular disease.

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References

  1. Giustina A, Barkan A, Beckers A, Biermasz N, Biller BMK, Boguszewski C, et al. A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 2020;105(4):e937–46. dgz096. https://doi.org/10.1210/clinem/dgz096.

    Article  Google Scholar 

  2. Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989;10(1):68–91. https://doi.org/10.1210/edrv-10-1-68.

    Article  CAS  PubMed  Google Scholar 

  3. Isaksson OG, Lindahl A, Nilsson A, Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev. 1987;8(4):426–38. https://doi.org/10.1210/edrv-8-4-426.

    Article  CAS  PubMed  Google Scholar 

  4. Berg C, Petersenn S, Lahner H, Herrmann BL, Buchfelder M, Droste M, et al. Investigators, cardiovascular risk factors in patients with uncontrolled and long-term acromegaly, comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab. 2010;95:3648–56. https://doi.org/10.1210/jc.2009-2570.

    Article  CAS  PubMed  Google Scholar 

  5. Hannon AM, Thompson CJ, Sherlock M. Diabetes in patients with acromegaly. Curr Diab Rep. 2017;17(2):8. https://doi.org/10.1007/s11892-017-0838-7.

    Article  CAS  PubMed  Google Scholar 

  6. Lombardi G, Di Somma C, Grasso LF, Savanelli MC, Colao A, Pivonello R. The cardiovascular system in growth hormone excess and growth hormone deficiency. J Endocrinol Investig. 2012;35(11):1021–9. https://doi.org/10.3275/8717.

    Article  CAS  Google Scholar 

  7. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-1) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo study. J Clin Endocrinol Metab. 2004;89(1):114–20.

    Article  CAS  Google Scholar 

  8. Svensson J, Carlzon D, Petzold M, Karlsson MK, Ljungren Ö, Tivesten A, et al. Both low and high serum IGF-1 levels associate with cancer mortality in older men. J Clin Endocrinol Metab. 2012;97(12):4623–30. https://doi.org/10.1210/jc.2012-2329.

    Article  CAS  PubMed  Google Scholar 

  9. van Bunderen CC, van Nieuwpoort IC, van Schoor NM, Deeg DJ, Lips P, Drent ML. The association of serum insulin-like growth factor-I with mortality, cardiovascular disease, and cancer in the elderly: a population-based study. J Clin Endocrinol Metab. 2010;95(10):4616–24. https://doi.org/10.1210/jc.2010-0940.

    Article  CAS  PubMed  Google Scholar 

  10. Kamenicky P, Blanchard A, Frank M, Salenave S, Letierce A, Azizi M, et al. Body fluid expansion in acromegaly is related to enhanced epithelial sodium channel (ENaC) activity. J Clin Endocrinol Metab. 2011;96(9):2796–804. https://doi.org/10.1210/jc.2011-0536.

    Article  CAS  PubMed  Google Scholar 

  11. Mosca S, Paolillo S, Colao A, Bossone E, Cittadini A, Iudice FL, et al. Cardiovascular involvement in patients affected by acromegaly, an appraisal. Int J Cardiol. 2013;167(5):1712–8. https://doi.org/10.1016/j.ijcard.2012.11.109.

    Article  PubMed  Google Scholar 

  12. Larsson SC, Michaëlsson K, Burgess S. IGF-1 and cardiometabolic diseases: a Mendelian randomisation study. Diabetologia. 2020;63(9):1775–82. https://doi.org/10.1007/s00125-020-05190-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lewitt MS, Hilding A, Brismar K, Efendic S, Ostenson CG, Hall K. IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women. Eur J Endocrinol. 2010;163(2):233–42. https://doi.org/10.1530/EJE-10-0301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Similä ME, Kontto JP, Virtamo J, Hätönen KA, Valsta LM, Sundvall J, et al. Insulin-like growth factor I, binding proteins −1 and −3, risk of type 2 diabetes and macronutrient intakes in men. Br J Nutr. 2019;121(8):938–44. https://doi.org/10.1017/S0007114519000321.

    Article  CAS  PubMed  Google Scholar 

  15. Colao A. 5 Long-term acromegaly and associated cardiovascular complications: a case-based review. Best Pract Res Clin Endocrinol Metab. 2009;23 Suppl 1:S31–8. https://doi.org/10.1016/S1521-690X(09)70006-5.

    Article  PubMed  Google Scholar 

  16. Orme SM, McNally RJQ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. J Clin Endocrinol Metab. 1998;83(8):2730–4. https://doi.org/10.1210/jcem.83.8.5007.

    Article  CAS  PubMed  Google Scholar 

  17. Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS. Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. Eur J Endocrinol. 2018;179(1):59–71.

    Article  CAS  Google Scholar 

  18. Castellano G, Affuso F, Di Conza P, Fazio S. The GH/IGF-1 axis and heart failure. Curr Cardiol Rev. 2009;5(3):203–15. https://doi.org/10.2174/157340309788970306.-.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Timsit J, Riou B, Bertherat J, Wisnewsky C, Kato NS, Weisberg AS, et al. Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle. J Clin Invest. 1990;86(2):507–15. https://doi.org/10.1172/JCI114737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Saccà L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev. 1994;15(5):555–73. https://doi.org/10.1210/edrv-15-5-555.

    Article  PubMed  Google Scholar 

  21. Colao A, Marzullo P, Di Somma C, Lombardi G. Growth hormone and the heart. Clin Endocrinol. 2001;54(2):137–54. https://doi.org/10.1046/j.1365-2265.2001.01218.x.

    Article  CAS  Google Scholar 

  22. Zada G, Kelly DF, Cohan P, Wang C, Swerdloff R. Endonasal transsphenoidal approach to treat pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions of the surgery. J Neurosurg. 2003;98(2):350–8. https://doi.org/10.3171/jns.2003.98.2.0350.

    Article  PubMed  Google Scholar 

  23. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, et al. Treatment of acromegaly with the growth hormone–receptor antagonist pegvisomant. N Engl J Med. 2000;342(16):1171–7. https://doi.org/10.1056/NEJM200004203421604.

    Article  CAS  PubMed  Google Scholar 

  24. Chanson P. Medical treatment of acromegaly with dopamine agonists or somatostatin analogs. Neuroendocrinology. 2015;103(1):50–8. https://doi.org/10.1159/000377704.

    Article  CAS  PubMed  Google Scholar 

  25. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89(2):667–74. https://doi.org/10.1210/jc.2003-031199.

    Article  CAS  PubMed  Google Scholar 

  26. Suzuki H, Kusuyama T, Omori Y, Soda T, Tsunoda F, Sato T, et al. Inhibitory effect of candesartan cilexetil on left ventricular remodeling after myocardial infarction. Int Heart J. 2006;47(5):715–25. https://doi.org/10.1536/ihj.47.715.

    Article  CAS  PubMed  Google Scholar 

  27. Thomas JDJ, Dattani A, Zemrak F, Burchell T, Akker SA, Kaplan FJL, et al. Renin-angiotensin system blockade improves cardiac indices in acromegaly patients. Exp Clin Endocrinol Diabetes. 2017;125(6):365–7. https://doi.org/10.1055/s-0042-123710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Marks P, Vincent R, Wilson B, Delassale A. Aldosterone in acromegaly. Am J Med Sci. 1984;287(3):16–9. https://doi.org/10.1097/00000441-198405000-00005.

    Article  CAS  PubMed  Google Scholar 

  29. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling-concepts and clinical implications: a consensus paper from an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569–82. https://doi.org/10.1016/s0735-1097(99)00630-0.

    Article  CAS  PubMed  Google Scholar 

  30. Ezzat S, Forster MJ, Berchtold P, Redelmeier DA, Boerlin V, Harris AG. Acromegaly. Clinical and biochemical features in 500 patients. Medicine (Baltimore). 1994;73(5):233–40.

    Article  CAS  Google Scholar 

  31. Esposito D, Ragnarsson O, Johannsson G, Olsson DS. Prolonged diagnostic delay in acromegaly is associated with increased morbidity and mortality. Eur J Endocrinol. 2020;182(6):523–31. https://doi.org/10.1530/EJE-20-0019. PMID: 32213651.

    Article  CAS  PubMed  Google Scholar 

  32. Dutta P, Hajela A, Gupta P, Rai A, Sachdeva N, Mukherjee KK, et al. The predictors of recovery from diabetes mellitus following neurosurgical treatment of acromegaly: a prospective study over a decade. Neurol India. 2019;67(3):757–62. https://doi.org/10.4103/0028-3886.263242.

    Article  PubMed  Google Scholar 

  33. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. https://doi.org/10.1056/NEJMoa1603827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. https://doi.org/10.1056/NEJMoa1607141.

    Article  CAS  PubMed  Google Scholar 

  35. Liu J, Li L, Li S, Wang Y, Qin X, Deng K, et al. Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22(9):1619–27. https://doi.org/10.1111/dom.14075.

    Article  CAS  PubMed  Google Scholar 

  36. Quarella M, Walser D, Brändle M, Fournier JY, Bilz S. Rapid onset of diabetic ketoacidosis after SGLT2 inhibition in a patient with unrecognized acromegaly. J Clin Endocrinol Metab. 2017;102(5):1451–3. https://doi.org/10.1210/jc.2017-00082.

    Article  PubMed  Google Scholar 

  37. Cozzolino A, Feola T, Simonelli I, Puliani G, Pozza C, Gianetta E, et al. Somatostatin analogs and glucose metabolism in acromegaly. A meta-analysis of prospective interventional studies. J Clin Endocrinol Metab. 2018;103(6):2089–99. https://doi.org/10.1210/jc.2017-02566.

    Article  Google Scholar 

  38. Sheppard M, Bronstein MD, Freda P, Serri O, De Marinis L, Naves L, et al. Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, phase III study. Pituitary. 2015;18(3):385–94. https://doi.org/10.1007/s11102-014-0585-6.

    Article  CAS  PubMed  Google Scholar 

  39. Gadelha MR, Gu F, Bronstein MD, Brue TC, Fleseriu M, Shimon I, et al. Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr Connect. 2020;9(12):1178–90. https://doi.org/10.1530/EC-20-0361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005;90(10):5684–91. https://doi.org/10.1210/jc.2005-0331.

    Article  CAS  PubMed  Google Scholar 

  41. Giustina A, Arnaldi G, Bogazzi F, Cannavò S, Colao A, De Marinis L, et al. Pegvisomant in acromegaly: an update. J Endocrinol Investig. 2017;40(6):577–89. https://doi.org/10.1007/s40618-017-0614-1.

    Article  CAS  Google Scholar 

  42. Brue T, Lindberg A, Jan van der Lely A, Akerblad AC, Koltowska-Häggström M, Gomez R, et al. Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy. Endocrine. 2019;63(3):563–72. https://doi.org/10.1007/s12020-018-1792-0.

    Article  CAS  PubMed  Google Scholar 

  43. Muhammad A, van der Lely AJ, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen J, et al. Efficacy and safety of switching to pasireotide in patients with acromegaly treated with first generation somatostatin analogues (PAPE Study). J Clin Endocrinol Metab. 2018;103(2):586–95.

    Article  Google Scholar 

  44. Nikkilä EA, Pelkonen R. Serum lipids in acromegaly. Metabolism. 1975;24(7):829–38. https://doi.org/10.1016/0026-0495(75)90129-8.

    Article  PubMed  Google Scholar 

  45. Vilar L, Naves LA, Costa SS, Abdalla LF, Coelho CE, Casulari LA. Increase of classic and nonclassic cardiovascular risk factors in patients with acromegaly. Endocr Pract. 2007;13(4):363–72. https://doi.org/10.4158/EP.13.4.363.

    Article  PubMed  Google Scholar 

  46. Vilar L, Valenzuela A, Ribeiro-Oliveira A Jr, Gómez Giraldo CM, Pantoja D, Bronstein MD. Multiple facets in the control of acromegaly. Pituitary. 2014;17 Suppl 1(Suppl 1):S11–7. https://doi.org/10.1007/s11102-013-0536-7.

    Article  PubMed  Google Scholar 

  47. Newman CB, Blaha MJ, Boord JB, Cariou B, Chait A, Fein HG, et al. Lipid management in patients with endocrine disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2020;105(12):dgaa674. https://doi.org/10.1210/clinem/dgaa674.

    Article  PubMed  Google Scholar 

  48. Mishra M, Durrington P, Mackness M, Siddals KW, Kaushal K, Davies R, et al. The effect of atorvastatin on serum lipoproteins in acromegaly. Clin Endocrinol. 2005;62(6):650–5. https://doi.org/10.1111/j.1365-2265.2005.02273.x.

    Article  CAS  Google Scholar 

  49. Pivonello R, Auriemma RS, Grasso LF, Pivonello C, Simeoli C, Patalano R, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017;20(1):46–62. https://doi.org/10.1007/s11102-017-0797-7.

    Article  PubMed  Google Scholar 

  50. Vouzouneraki K, Franklin KA, Forsgren M, Wärn M, Persson JT, Wik H, et al. Temporal relationship of sleep apnea and acromegaly: a nationwide study. Endocrine. 2018;62(2):456–63. https://doi.org/10.1007/s12020-018-1694-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Al Lawati NM, Patel SR, Ayas NT. Epidemiology, risk factors, and consequences of obstructive sleep apnea and short sleep duration. Prog Cardiovasc Dis. 2009;51(4):285–93. https://doi.org/10.1016/j.pcad.2008.08.001.

    Article  PubMed  Google Scholar 

  52. Parolin M, Dassie F, Alessio L, Wennberg A, Rossato M, Vettor R, et al. Obstructive sleep apnea in acromegaly and the effect of treatment: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2020;105(3):dgz116. https://doi.org/10.1210/clinem/dgz116.

    Article  PubMed  Google Scholar 

  53. Carvalho P, Lau E, Carvalho D. Surgery induced hypopituitarism in acromegalic patients: a systematic review and meta-analysis of the results. Pituitary. 2015;18(6):844–60. https://doi.org/10.1007/s11102-015-0652-7.

    Article  CAS  PubMed  Google Scholar 

  54. Jenkins PJ, Bates P, Carson MN, Stewart PM, Wass JA. Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. J Clin Endocrinol Metab. 2006;91(4):1239–45. https://doi.org/10.1210/jc.2005-1616.

    Article  CAS  PubMed  Google Scholar 

  55. Crown A, Lightman S. Why is the management of glucocorticoid deficiency still controversial: a review of the literature. Clin Endocrinol. 2005;63(5):483–92. https://doi.org/10.1111/j.1365-2265.2005.02320.x.

    Article  CAS  Google Scholar 

  56. Mazziotti G, Formenti AM, Frara S, Roca E, Mortini P, Berruti A, et al. Management of endocrine disease: risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects. Eur J Endocrinol. 2017;177(5):R231–48. https://doi.org/10.1530/EJE-17-0154.

    Article  CAS  PubMed  Google Scholar 

  57. Klose M, Marina D, Hartoft-Nielsen ML, 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(9):3802–10. https://doi.org/10.1210/jc.2013-1610.

    Article  CAS  PubMed  Google Scholar 

  58. Çatakoğlu AB, Kendirci M. Testosterone replacement therapy and cardiovascular events. Turk Kardiyol Dern Ars. 2017;45(7):664–72. https://doi.org/10.5543/tkda.2017.00531.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pituitary Center, Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH, USA

    Divya Yogi-Morren & Laurence Kennedy

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  1. Divya Yogi-Morren
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Correspondence to Divya Yogi-Morren .

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  1. Mayo Clinic, Jacksonville, FL, USA

    Susan L. Samson

  2. Emory University School of Medicine, Atlanta, GA, USA

    Adriana G. Ioachimescu

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Yogi-Morren, D., Kennedy, L. (2022). Minimizing Cardiometabolic Risk Factors in Patients with Acromegaly. In: Samson, S.L., Ioachimescu, A.G. (eds) Pituitary Disorders throughout the Life Cycle. Springer, Cham. https://doi.org/10.1007/978-3-030-99918-6_21

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