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Is there an association between non-functioning adrenal adenoma and endothelial dysfunction?

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Abstract

Background and aim: Subtle changes in hypothalamic-pituitary-adrenal (HPA) axis of subjects with non-functioning adrenal adenoma may be associated with endothelial alterations. We sought to investigate endothelial function, visceral adiposity and osteoprotegerin (OPG) and interleukin-18 (IL-18) levels in subjects with non-functioning adrenal adenomas. Subjects and methods: The adenoma group included 40 subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders. Twenty-two body mass index-matched controls were also enroled. The patients and control subjects underwent hormonal evaluation and assessment of anthropometric and metabolic parameters. Endothelial function was assessed with flow-mediated dilatation (FMD) of the brachial artery and intima media thickness (IMT) of common carotid arteries. Visceral adipose tissue area was measured by computed tomography. Plasma OPG and serum IL-18 levels were also measured. Results: When compared with healthy controls, the adenoma group had elevated systolic blood pressure, post-dexamethasone suppression test cortisol and reduced DHEAS. Visceral adipose tissue area and IMT of common carotid arteries were comparable. In the adenoma group, FMD of the brachial artery was significantly impaired and IL-18 level was significantly elevated. Visceral adipose tissue area was independently related with FMD. Homeostasis model assessment (HOMA) was the independent factor associated with visceral adipose tissue area. Cortisol, DHEAS and visceral adipose tissue area were independently associated with HOMA. Conclusions: We achieved evidence that could be attributable to endothelial alterations in subjects with non-functioning adrenal adenomas. Impaired FMD appeared to be a consequence of subtle changes in HPA axis in terms of elevated cortisol and reduced DHEAS as these conditions were known to disturb endothelial-dependent vasodilatation.

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References

  1. Rossi R, Tauchmanova L, Luciano A, et al. Subclinical Cushing’s syndrome in patients with adrenal incidentaloma: clinical and biochemical features. J Clin Endocrinol Metab 2000, 85: 1440–8.

    PubMed  CAS  Google Scholar 

  2. Tauchmanovà L, Rossi R, Biondi B, et al. Patients with subclinical Cushing’s syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab 2002, 87: 4872–8.

    Article  PubMed  CAS  Google Scholar 

  3. Terzolo M, Bovio S, Reimondo G, et al., Subclinical Cushing’s syndrome in adrenal incidentalomas. Endocrinol Metab Clin North Am 2005, 34: 423–39, x.

    Article  PubMed  Google Scholar 

  4. Terzolo M, Pia A, Alì A, Osella G, et al. Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab 2002, 87: 998–1003.

    Article  PubMed  CAS  Google Scholar 

  5. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab 2000, 85: 637–44.

    PubMed  CAS  Google Scholar 

  6. Ermetici F, Malavazos AE, Corbetta S, et al. Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. Metabolism 2007, 56: 686–92.

    Article  PubMed  CAS  Google Scholar 

  7. Yener S, Genc S, Akinci B, et al. Carotid intima media thickness is increased and associated with morning cortisol in subjects with non-functioning adrenal incidentaloma. Endocrine 2009, 35: 365–70.

    Article  PubMed  CAS  Google Scholar 

  8. Sartorio A, Conti A, Ferrero S, et al. Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing’s syndrome and in patients with adrenal incidentaloma. Eur J Endocrinol 1998, 138: 146–52.

    Article  PubMed  CAS  Google Scholar 

  9. Walker BR. Glucocorticoids and cardiovascular disease. Eur J Endocrinol 2007, 157: 545–59.

    Article  PubMed  CAS  Google Scholar 

  10. Terzolo M, Bovio S, Pia A, et al. Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur J Endocrinol 2005, 153: 307–15.

    Article  PubMed  CAS  Google Scholar 

  11. Lane HA, Smith JC, Davies JS. Noninvasive assessment of preclinical atherosclerosis. Vasc Health Risk Manag 2006, 2: 19–30.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Nadar S, Blann AD, Lip GY. Endothelial dysfunction: methods of assessment and application to hypertension. Curr Pharm Des 2004, 10: 3591–605.

    Article  PubMed  CAS  Google Scholar 

  13. Terzolo M, Reimondo G, Bovio S, Angeli A. Subclinical Cushing’s syndrome. Pituitary 2004, 7: 217–23.

    Article  PubMed  Google Scholar 

  14. Formoso G, Chen H, Kim JA, Montagnani M, Consoli A, Quon MJ. Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium. Mol Endocrinol 2006, 20: 1153–63.

    Article  PubMed  CAS  Google Scholar 

  15. Liu D, Si H, Reynolds KA, Zhen W, Jia Z, Dillon JS. Dehydroepiandrosterone protects vascular endothelial cells against apoptosis through a Galphai protein-dependent activation of phosphatidylinositol 3-kinase/Akt and regulation of antiapoptotic Bcl-2 expression. Endocrinology 2007, 148: 3068–76.

    Article  PubMed  CAS  Google Scholar 

  16. Simoncini T, Mannella P, Fornari L, Varone G, Caruso A, Genazzani AR. Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms. Endocrinology 2003, 144: 3449–55.

    Article  PubMed  CAS  Google Scholar 

  17. Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab 2003, 88: 3190–5.

    Article  PubMed  CAS  Google Scholar 

  18. Williams MR, Dawood T, Ling S, et al. Dehydroepiandrosterone increases endothelial cell proliferation in vitro and improves endothelial function in vivo by mechanisms independent of androgen and estrogen receptors. J Clin Endocrinol Metab 2004, 89: 4708–15.

    Article  PubMed  CAS  Google Scholar 

  19. Liu D, Iruthayanathan M, Homan LL, et al. Dehydroepiandrosterone stimulates endothelial proliferation and angiogenesis through extracellular signal-regulated kinase 1/2-mediated mechanisms. Endocrinology 2008, 149: 889–98.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Mangos GJ, Walker BR, Kelly JJ, Lawson JA, Webb DJ, Whitworth JA. Cortisol inhibits cholinergic vasodilation in the human forearm. Am J Hypertens 2000, 13: 1155–60.

    Article  PubMed  CAS  Google Scholar 

  21. Ohman MK, Wright AP, Wickenheiser KJ, Luo W, Eitzman DT. Visceral adipose tissue and atherosclerosis. Curr Vasc Pharmacol 2009, 7: 169–79.

    Article  PubMed  CAS  Google Scholar 

  22. Girard J, Lafontan M. Impact of visceral adipose tissue on liver metabolism and insulin resistance. Part II: Visceral adipose tissue production and liver metabolism. Diabetes Metab 2008, 34: 439–45.

    Article  PubMed  CAS  Google Scholar 

  23. Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor detect of insulin action. J Clin Endocrinol Metab 1982, 54: 131–8.

    Article  PubMed  CAS  Google Scholar 

  24. Whorwood CB, Donovan SJ, Flanagan D, Phillips DI, Byrne CD. Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome. Diabetes 2002, 51: 1066–75.

    Article  PubMed  CAS  Google Scholar 

  25. Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008, 54: 24–38.

    Article  PubMed  CAS  Google Scholar 

  26. Blankenberg S, Luc G, Ducimetière P, et al. Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003, 108: 2453–9.

    Article  PubMed  CAS  Google Scholar 

  27. Blankenberg S, Tiret L, Bickel C, et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 2002, 106: 24–30.

    Article  PubMed  CAS  Google Scholar 

  28. Rabkin SW. The role of interleukin 18 in the pathogenesis of hypertension-induced vascular disease. Nat Clin Pract Cardiovasc Med 2009, 6: 192–9.

    Article  PubMed  CAS  Google Scholar 

  29. Dovio A, Allasino B, Palmas E, et al. Increased osteoprotegerin levels in Cushing’s syndrome are associated with an adverse cardiovascular risk profile. J Clin Endocrinol Metab 2007, 92: 1803–8.

    Article  PubMed  CAS  Google Scholar 

  30. Kiechl S, Schett G, Wenning G, et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 2004, 109: 2175–80.

    Article  PubMed  CAS  Google Scholar 

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Yener, S., Baris, M., Secil, M. et al. Is there an association between non-functioning adrenal adenoma and endothelial dysfunction?. J Endocrinol Invest 34, 265–270 (2011). https://doi.org/10.1007/BF03347083

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