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Cardiovascular risk in adult hypopituitaric patients with growth hormone deficiency: is there a role for vitamin D?

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Abstract

Hypovitaminosis D represent an environmental risk factors for cardiovascular (CV) disease. To investigate the prevalence of hypovitaminosis D and the correlation between GH/IGF-I deficiency and hypovitaminosis D with CV risk in GH deficiency (GHD) patients. A link between these hormones has been shown. Forty-one hypopituitaric patients with GHD (22 males, age 18–84 years) and 41 controls were enrolled in the study. Anthropometric parameters, blood pressure, glucose and lipid profile, parathyroid hormone (PTH), 25(OH) vitamin D (vitamin D), metabolic syndrome (MS), GH peak after GHRH + ARG, IGF-I, and standard deviation score (SDS) of IGF-I (zIGF-I) were assessed. Vitamin D levels were lower in patients than in controls (21.3 ± 12.3 vs. 28.2 ± 9.4, p = 0.006). Deficiency was found in 51 % of patients versus 14.6 % of controls (p < 0.01), insufficiency in 26.8 versus 41.4 % (p = 0.269) and normal vitamin D levels in 21.9 versus 43.9 % (p = 0.060). The prevalence of dyslipidemia was 51.2 % in patients versus 12.1 % in controls (p < 0.001), type 2 diabetes mellitus (DM) was 7.3 versus 17 % (p = 0.292), hypertension was 44 versus 22 % (p = 0.060), and MS was 17 versus 14.6 % (p = 0.957). In patients, an association was found between the presence of hypovitaminosis D and the prevalence of dyslipidemia, hypertension and MS and between zIGF-I and the prevalence of hypertension. Hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension. GHD patients have an increased prevalence of hypovitaminosis D compared with controls. The presence of hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension in GHD patients, suggesting the involvement of both factors in the CV risk in these patients.

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References

  1. P. Pludowski, M.F. Holick, S. Pilz, C.L. Wagner, B.W. Hollis, W.B. Grant, Y. Shoenfeld, E. Lerchbaum, D.J. Llewellyn, K. Kienreich, M. Soni, Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun. Rev. (2013). doi:10.1016/j.autrev.2013.02.004

    PubMed  Google Scholar 

  2. R. Bouillon, L. Verlinden, Does a better vitamin D status help to reduce cardiovascular risks and events? Endocrine (2014). doi:10.1007/s12020-014-0429-1

    PubMed  Google Scholar 

  3. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine (2013). doi:10.1007/s12020-012-9805-x

    Google Scholar 

  4. J. Merke, P. Milde, S. Lewicka, U. Hugel, G. Klaus, D.J. Mangelsdorf, M.R. Haussler, E.W. Rauterberg, E. Ritz, Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25- dihydroxyvitamin D3: studies in cultured bovine aortic endothelial cells and human dermal capillaries. J. Clin. Invest. 83(6), 1903–1915 (1989)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. D. Somjen, Y. Weisman, F. Kohen, B. Gayer, R. Limor, O. Sharon, N. Jaccard, E. Knoll, N. Stern, 25-Hydroxyvitamin D3-1alpha-hydroxylase is espresse in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation 111(13), 1666–1671 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. R. Simpson, G. Thomas, A. Arnold, Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J. Biol. Chem. 260(15), 8882–8891 (1985)

    CAS  PubMed  Google Scholar 

  7. G. Muscogiuri, G.P. Sorice, R. Ajjan, T. Mezza, S. Pilz, A. Prioletta, R. Scragg, S.L. Volpe, M.D. Witham, A. Giaccari, Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives. Nutr. Metab. Cardiovasc. Dis. 22(2), 81–87 (2012)

    Article  CAS  PubMed  Google Scholar 

  8. R. Scragg, R. Jackson, I.M. Holdaway, T. Lim, R. Beaglehole, Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int. J. Epidemiol. 19(3), 559–563 (1990)

    Article  CAS  PubMed  Google Scholar 

  9. S. Pilz, H. Dobnig, J.E. Fischer, B. Wellnitz, U. Seelhorst, B.O. Boehm, W. Ma¨rz, Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke 39(9), 2611–2613 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. J.H. Lee, J.H. O’Keefe, D. Bell, D.D. Hensrud, M.F. Holick, Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J. Am. Coll. Cardiol. (2008). doi:10.1016/j.jacc.2008.08.050

    PubMed Central  Google Scholar 

  11. M.L. Melamed, P. Muntner, E.D. Michos, J. Uribarri, C. Weber, J. Sharma, P. Raggi, Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004. Arterioscler. Thromb. Vasc. Biol. (2008). doi:10.1161/ATVBAHA.108.165886

    PubMed  PubMed Central  Google Scholar 

  12. D. Martins, M. Wolf, D. Pan, A. Zadshir, N. Tareen, R. Thadhani, A. Felsenfeld, B. Levine, R. Mehrotra, K. Norris, Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch. Intern. Med. 167(11), 1159–1165 (2007)

    Article  CAS  PubMed  Google Scholar 

  13. Muscogiuri G. Nuzzo, V. Gatti, A. Zuccoli, A., Savastano, S., Di Somma, C. Pivonello, R. Orio, F. Colao, A.: Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes?. Endocrine. (2015)

  14. G. Targher, I. Pichiri, G. Lippi, Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin. Thromb. Hemost. 38(1), 114–124 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. V. Carnevale, R. Minonne, A. De Matthaeis, M.A. Annese, P. Tabacco, P. D’Arcangelo, G. D’Amico, A. Scillitani, Carotid intima-media thickness is not associated with vitamin D and PTH levels in patients admitted to an Internal Medicine Department. Endocrine (2014). doi:10.1007/s12020-014-0191-4

    Google Scholar 

  16. L. Giovannini, G. Tirabassi, G. Muscogiuri, C. Di Somma, A. Colao, G. Balercia, Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]. Endocr. J. (2015). doi:10.1507/endocrj.EJ15-0337

    PubMed  Google Scholar 

  17. A. Colao, The GH–IGF-I axis and the cardiovascular system: clinical implications. Clin. Endocrinol. (Oxf) (2008). doi:10.1111/j.1365-2265.2008.03292.x

    Google Scholar 

  18. A. Juul, T. Scheike, M.J. Davidsen, T. Gyllenborg, J.O. Jorgensen, Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case–control study. Circulation 106(8), 939–944 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. G.A. Laughlin, E. Barrett-Connor, M.H. Criqui, D. Kritz-Silverstein, The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J. Clin. Endocrinol. Metab. 89(1), 114–120 (2004)

    Article  CAS  PubMed  Google Scholar 

  20. S.P. Johnsen, H.H. Hundborg, H.T. Sorensen, H. Orskov, A. Tjonneland, K. Overvad, J.O. Jorgensen, Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke. J. Clin. Endocrinol. Metab. 90(11), 5937–5941 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. M. Bondanelli, M.R. Ambrosio, A. Onofri, A. Bergonzoni, S. Lavezzi, M.C. Zatelli, D. Valle, N. Basaglia, E.C. Degli Uberti, Predictive value of circulating insulin-like growth factor I levels in ischemic stroke outcome. J. Clin. Endocrinol. Metab. 91(10), 3928–3934 (2006)

    Article  CAS  PubMed  Google Scholar 

  22. A.W. Van den Beld, M.L. Bots, J.A. Janssen, H.A. Pols, S.W. Lamberts, D.E. Grobbee, Endogenous hormones and carotid atherosclerosis in elderly men. Am. J. Epidemiol. 157(1), 25–31 (2003)

    Article  PubMed  Google Scholar 

  23. A. Colao, S. Spiezia, C. Di Somma, R. Pivonello, P. Marzullo, F. Rota, T. Musella, R.S. Auriemma, M.C. De Martino, G. Lombardi, Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age. J. Endocrinol. Invest. 28(5), 440–448 (2005)

    Article  CAS  PubMed  Google Scholar 

  24. A. Colao, C. Di Somma, T. Cascella, R. Pivonello, G. Vitale, L.F. Grasso, G. Lombardi, S. Savastano, Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects. Eur. J. Endocrinol. (2008). doi:10.1530/EJE-08-0201

    Google Scholar 

  25. T. Rosen, B.A. Bengtsson, Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336(8710), 285–288 (1990)

    Article  CAS  PubMed  Google Scholar 

  26. J.W. Tomlinson, N. Holden, R.K. Hills, K. Wheatleym, R.N. Clayton, A.S. Bates, M.C. Sheppard, P.M. Stewart, Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357(9254), 425–431 (2001)

    Article  CAS  PubMed  Google Scholar 

  27. P. Ameri, A. Giusti, M. Boschetti, G. Murialdo, F. Minuto, D. Ferone, Interactions between vitamin D and IGF-I: from physiology to clinical practice. Clin. Endocrinol. (Oxf) (2013). doi:10.1111/cen.12268

    Google Scholar 

  28. J.M. Gómez, Th role of insulin-like growth factor I components in the regulation of vitamin D. Curr. Pharm. Biotechnol. 7(2), 125–132 (2006)

    Article  PubMed  Google Scholar 

  29. L. Peng, P.J. Malloy, D. Feldman, Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter. Mol. Endocrinol. 18(5), 1109–1119 (2004)

    Article  CAS  PubMed  Google Scholar 

  30. S. Burstein, I. Chen, R.C. Tsang, Effects of growth hormone replacement therapy on 1,25-dihydroxyvitamin D and calcium metabolism. J. Clin. Endocrinol. Metab. 56(6), 1246–1251 (1983)

    Article  CAS  PubMed  Google Scholar 

  31. N.M. Wright, N. Papadea, B. Wentz, B. Hollis, S. Willi, N.H. Bell, Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated. Calcif. Tissue Int. 61(2), 101–103 (1997)

    Article  CAS  PubMed  Google Scholar 

  32. M. Fernández-Cancio, L. Audi, A. Carrascosa, N. Toran, P. Andaluz, C. Esteban, M.L. Granada, Vitamin D and growth hormone regulate growth hormone/insulin-like growth factor (GH-IGF) axis gene expression in human fetal epiphyseal chondrocytes. Growth Horm. IGF Res. (2009). doi:10.1016/j.ghir.2008.10.004

    PubMed  Google Scholar 

  33. J.M. Gómez, F.J. Maravall, N. Gómez, M.A. Navarro, R. Casamitjana, J. Soler, Relationship between 25-(OH) D3, the IGF-I system, leptin, anthropometric and body composition variables in a healthy, randomly selected population. Horm. Metab. Res. 36(1), 48–53 (2004)

    Article  PubMed  Google Scholar 

  34. E. Hyppönen, B.J. Boucher, D.J. Berry, C. Power, 25-hydroxyvitamin D, IGF-I, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes 57(2), 298–305 (2008)

    Article  PubMed  Google Scholar 

  35. F. Bogazzi, G. Rossi, M. Lombardi, L. Tomisti, C. Sardella, L. Manetti, O. Curzio, C. Marcocci, L. Grasso, M. Gasperi, E. Martino, Vitamin D status may contribute to serum insulin-like growth factor I concentrations in healthy subjects. J. Endocrinol. Invest. (2011). doi:10.3275/7228

    Google Scholar 

  36. K.G. Alberti, P. Zimmet, J. Shaw, The metabolic syndrome–a new worldwide definition. Lancet 366, 1059–1062 (2005)

    Article  PubMed  Google Scholar 

  37. M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96(7), 1911–1930 (2011)

    Article  CAS  PubMed  Google Scholar 

  38. G. Corneli, C. Di Somma, R. Baldelli, S. Rovere, V. Gasco, C.G. Croce, S. Grottoli, M. Maccario, A. Colao, G. Lombardi, E. Ghigo, F. Camanni, G. Aimaretti, The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur. J. Endocrinol. 153(2), 257–264 (2005)

    Article  CAS  PubMed  Google Scholar 

  39. A. Colao, C. Di Somma, S. Savastano, F. Rota, M.C. Savanelli, G. Aimaretti, G. Lombardi, A reappraisal of diagnosing GH deficiency in adults: role of gender, age, waist circumference, and body mass index. J. Clin. Endocrinol. Metab. (2009). doi:10.1210/jc.2009-1134

    Google Scholar 

  40. K.K. Ho, GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur. J. Endocrinol. 157, 695–700 (2007)

    Article  CAS  PubMed  Google Scholar 

  41. S. Savastano, L. Angrisani, C. Di Somma, F. Rota, M.C. Savanelli, T. Cascella, F. Orio, G. Lombardi, A. Colao, Relationship between growth hormone/insulin-like growth factor-1 axis integrity and voluntary weight loss after gastric banding surgery for severe obesity. Obes. Surg. (2010). doi:10.1007/s11695-009-9926-3

    Google Scholar 

  42. P. Ameri, A. Giusti, M. Boschetti, M. Bovio, C. Teti, G. Leoncini, D. Ferone, G. Murialdo, F. Minuto, Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency. Eur. J. Endocrinol. (2013). doi:10.1530/EJE-13-0510

    PubMed  Google Scholar 

  43. J.M. Pascussi, A. Robert, M. Nguyen, O. Walrant-Debray, M. Garabedian, P. Martin, T. Pineau, J. Saric, F. Navarro, P. Maurel, M.J. Vilarem, Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J. Clin. Invest. 115(1), 177–186 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. G. Sarno, G. Daniele, G. Tirabassi, A.O. Chavez, O.O. Ojo, F. Orio, H. Kahleova, G. Balercia, W.B. Grant, P. De Rosa, A. Colao, G. Muscogiuri, The impact of vitamin D deficiency on patients undergoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes. Endocrine (2015). doi:10.1007/s12020-015-0632-8

    PubMed  Google Scholar 

  45. R. Jorde, G. Grimnes, Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog. Lipid Res. (2011). doi:10.1016/j.plipres.2011.05.001

    PubMed  Google Scholar 

  46. S. Jaimungal, K. Wehmeier, A.D. Mooradian, M.J. Haas, The emerging evidence for vitamin D-mediated regulation of apolipoprotein A-I synthesis. Nutr. Res. (2011). doi:10.1016/j.nutres.2011.09.005

    PubMed  Google Scholar 

  47. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population. Cardiology (2012). doi:10.1159/000341277

    PubMed  Google Scholar 

  48. S.N. Rajpathak, X. Xue, S. Wassertheil-Smoller, L. Van Horn, J.G. Robinson, S. Liu, M. Allison, L.W. Martin, G.Y. Ho, T.E. Rohan, Effect of 5 y of calcium plus vitamin D supplementation on change in circulating lipids: results from the Women’s Health Initiative. Am. J. Clin. Nutr. (2010). doi:10.3945/ajcn.2009.28579

    PubMed  PubMed Central  Google Scholar 

  49. S.G. Rostand, Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension 30(2 Pt 1), 150–156 (1997)

    Article  CAS  PubMed  Google Scholar 

  50. A.G. Pittas, M. Chung, T. Trikalinos, J. Mitri, M. Brendel, K. Patel, A.H. Lichtenstein, J. Lau, E.M. Balk, Systematic review: vitamin D and cardiometabolic outcomes. Ann. Intern. Med. 152(5), 307–314 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  51. S.K. Kunutsor, T.A. Apekey, M. Steur, Vitamin D and risk of future hypertension: meta-analysis of 283,537 participants. Eur. J. Epidemiol. 28(3), 205–221 (2013)

    Article  CAS  PubMed  Google Scholar 

  52. J.P. Forman, J.S. Williams, N.D. Fisher, Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. Hypertension 55(5), 1283–1288 (2010). doi:10.1161/HYPERTENSIONAHA.109.148619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. K.L. Margolis, L.W. Martin, R.M. Ray, T.J. Kerby, M.A. Allison, J.D. Curb, T.A. Kotchen, S. Liu, S. Wassertheil-Smoller, J.E. Manson, Women’s Health Initiative Investigators, A prospective study of serum 25-hydroxyvitamin D levels, blood pressure, and incident hypertension in postmenopausal women. Am. J. Epidemiol. (2012). doi:10.1093/aje/kwr274

    Google Scholar 

  54. L.A. Beveridge, M.D. Witham, Controversy in the link between vitamin D supplementation and hypertension. Expert Rev. Cardiovasc. Ther. (2015). doi:10.1586/14779072.2015.1065729

    PubMed  Google Scholar 

  55. R.C. Strange, K.E. Shipman, S. Ramachandran, Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J. Diabetes (2015). doi:10.4239/wjd.v6.i7.896

    PubMed  PubMed Central  Google Scholar 

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  1. IOS & Coleman Srl, Naples, Italy

    Maria Cristina Savanelli & Luigi Barrea

  2. Dipartimento di Medicina Clinica e Chirurgia, Section of Endocrinology, University “Federico II”, Naples, Italy

    Elisabetta Scarano, Giovanna Muscogiuri, Laura Vuolo, Manila Rubino, Silvia Savastano & Annamaria Colao

  3. IRCCS SDN, Naples, Italy

    Carolina Di Somma

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Savanelli, M.C., Scarano, E., Muscogiuri, G. et al. Cardiovascular risk in adult hypopituitaric patients with growth hormone deficiency: is there a role for vitamin D?. Endocrine 52, 111–119 (2016). https://doi.org/10.1007/s12020-015-0779-3

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