Skip to main content
Erschienen in: Wiener klinische Wochenschrift 3-4/2022

13.07.2021 | original article

Non-functioning adrenal incidentalomas may increase toxic metabolites

verfasst von: Assis. Prof. Irfan Karahan, M.D., Prof. Senay Durmaz Ceylan, M.D., Assoc. Prof. Askin Gungunes, M.D., Assoc. Prof. Aydın Cifci, M.D., Fatih Eker, M.D., Prof. Ucler Kisa, M.D.

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 3-4/2022

Einloggen, um Zugang zu erhalten

Summary

Background

Non-functioning adrenal incidentaloma (NFAI) is a frequent diagnosis with increasing radiological tests. The emerging shreds of evidence showed that they might have negative cardiometabolic effects. The study aimed to investigate whether the toxic metabolites, asymmetric dimethylarginine (ADMA) levels, were altered in NFAI patients.

Methods

We included 43 NFAI patients and 41 controls with similar ages and body mass indices in the study. We compared plasma ADMA levels of both groups and noted the radiological features of NFAIs.

Results

The ADMA levels were significantly higher in NFAI patients than in the control group (307.04 ng/ml, range 81.89–577.7 ng/ml vs 192.54 ng/ml, range 70.61–440.26 ng/ml, p = 0.001). Nevertheless, we could not reach a significant correlation between ADMA levels and mass size.

Conclusion

The ADMA is known as a toxin and is increased in NFAI patients. NFAIs may not be innocent and may be considered a potential risk for the body. Further investigations were needed for more explanations.
Literatur
1.
Zurück zum Zitat Sherlock M, Scarsbrook A, Abbas A, et al. Adrenal incidentaloma. Endocr Rev. 2020;41(6):775–820.CrossRef Sherlock M, Scarsbrook A, Abbas A, et al. Adrenal incidentaloma. Endocr Rev. 2020;41(6):775–820.CrossRef
2.
Zurück zum Zitat Szychlińska M, Baranowska-Jurkun A, Matuszewski W, Wołos-Kłosowicz K, Bandurska-Stankiewicz E. Markers of subclinical cardiovascular disease in patients with adrenal incidentaloma. Medicina (Kaunas). 2020;56(2):69.CrossRef Szychlińska M, Baranowska-Jurkun A, Matuszewski W, Wołos-Kłosowicz K, Bandurska-Stankiewicz E. Markers of subclinical cardiovascular disease in patients with adrenal incidentaloma. Medicina (Kaunas). 2020;56(2):69.CrossRef
3.
Zurück zum Zitat Kakimoto Y, Shigenori A. Isolation and identification and hydroxylysine from human of NG3 NG- and NG3 WG-dimethyl-urine. J Biol Chem. 1970;245(21):5751–8.CrossRef Kakimoto Y, Shigenori A. Isolation and identification and hydroxylysine from human of NG3 NG- and NG3 WG-dimethyl-urine. J Biol Chem. 1970;245(21):5751–8.CrossRef
4.
Zurück zum Zitat Tain YL, Hsu CN. Toxic dimethylarginines: asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Toxins (Basel). 2017;9(3):92.CrossRef Tain YL, Hsu CN. Toxic dimethylarginines: asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Toxins (Basel). 2017;9(3):92.CrossRef
5.
Zurück zum Zitat Bode-Böger SM, Scalera F, Ignarro LJ. The l‑arginine paradox: Importance of the l‑arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007;114(3):295–306.CrossRef Bode-Böger SM, Scalera F, Ignarro LJ. The l‑arginine paradox: Importance of the l‑arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007;114(3):295–306.CrossRef
6.
Zurück zum Zitat Sorrenti V, Mazza F, Campisi A, Vanella L, Volti G, Giacomo C. High glucose-mediated imbalance of nitric oxide synthase and dimethylarginine dimethylaminohydrolase expression in endothelial cells. Curr Neurovasc Res. 2006;3(1):49–54.CrossRef Sorrenti V, Mazza F, Campisi A, Vanella L, Volti G, Giacomo C. High glucose-mediated imbalance of nitric oxide synthase and dimethylarginine dimethylaminohydrolase expression in endothelial cells. Curr Neurovasc Res. 2006;3(1):49–54.CrossRef
7.
Zurück zum Zitat Tain Y‑L, Kao Y‑H, Hsieh C‑S, et al. Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine. Free Radic Biol Med. 2010;49(6):1088–98.CrossRef Tain Y‑L, Kao Y‑H, Hsieh C‑S, et al. Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine. Free Radic Biol Med. 2010;49(6):1088–98.CrossRef
8.
Zurück zum Zitat Brands MW, Bell TD, Gibson B. Nitric oxide may prevent hypertension early in diabetes by counteracting renal actions of superoxide. Hypertension. 2004;43(1):57–63.CrossRef Brands MW, Bell TD, Gibson B. Nitric oxide may prevent hypertension early in diabetes by counteracting renal actions of superoxide. Hypertension. 2004;43(1):57–63.CrossRef
9.
Zurück zum Zitat Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol. 2004;24(6):1023–30.CrossRef Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol. 2004;24(6):1023–30.CrossRef
10.
Zurück zum Zitat Wolf A, Zalpour C, Theilmeier G, et al. Dietary L‑arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol. 1997;29(3):479–85.CrossRef Wolf A, Zalpour C, Theilmeier G, et al. Dietary L‑arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol. 1997;29(3):479–85.CrossRef
11.
Zurück zum Zitat Böger RH, Bode-Böger SM, Phivthong-Ngam L, et al. Dietary L‑arginine and α‑tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms. Atherosclerosis. 1998;141(1):31–43.CrossRef Böger RH, Bode-Böger SM, Phivthong-Ngam L, et al. Dietary L‑arginine and α‑tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms. Atherosclerosis. 1998;141(1):31–43.CrossRef
12.
Zurück zum Zitat Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88(11):4651–5.CrossRef Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88(11):4651–5.CrossRef
13.
Zurück zum Zitat Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol. 2007;36(5):520–8.CrossRef Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol. 2007;36(5):520–8.CrossRef
14.
Zurück zum Zitat Chen MF, Xie XM, Yang TL, et al. Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II. J Vasc Res. 2007;44(5):391–402.CrossRef Chen MF, Xie XM, Yang TL, et al. Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II. J Vasc Res. 2007;44(5):391–402.CrossRef
15.
Zurück zum Zitat Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–7.CrossRef Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–7.CrossRef
16.
Zurück zum Zitat Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4(4):41–51.CrossRef Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4(4):41–51.CrossRef
17.
Zurück zum Zitat Zhang L, Wan Y‑N, Zhao J‑H, et al. The association between systemic sclerosis, arginine and asymmetric dimethylarginine. Inflammation. 2015;38(1):218–23.CrossRef Zhang L, Wan Y‑N, Zhao J‑H, et al. The association between systemic sclerosis, arginine and asymmetric dimethylarginine. Inflammation. 2015;38(1):218–23.CrossRef
18.
Zurück zum Zitat Park MJ, Oh KS, Nho JH, Kim GY, Kim DI. Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation. Cell Biol Int. 2016;40(6):662–70.CrossRef Park MJ, Oh KS, Nho JH, Kim GY, Kim DI. Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation. Cell Biol Int. 2016;40(6):662–70.CrossRef
19.
Zurück zum Zitat Pekarova M, Kubala L, Martiskova H, et al. Asymmetric dimethylarginine regulates the lipopolysaccharide-induced nitric oxide production in macrophages by suppressing the activation of NF-kappaB and iNOS expression. Eur J Pharmacol. 2013;713(1–3):68–77.CrossRef Pekarova M, Kubala L, Martiskova H, et al. Asymmetric dimethylarginine regulates the lipopolysaccharide-induced nitric oxide production in macrophages by suppressing the activation of NF-kappaB and iNOS expression. Eur J Pharmacol. 2013;713(1–3):68–77.CrossRef
20.
Zurück zum Zitat Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. 2016;175(2):G1–G34.CrossRef Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. 2016;175(2):G1–G34.CrossRef
21.
Zurück zum Zitat Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323(1):22–7.CrossRef Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323(1):22–7.CrossRef
22.
Zurück zum Zitat Böger RH, Bode-Böger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998;98(18):1842–7.CrossRef Böger RH, Bode-Böger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998;98(18):1842–7.CrossRef
23.
Zurück zum Zitat Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88(6):2510–6.CrossRef Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88(6):2510–6.CrossRef
24.
Zurück zum Zitat Eid HMA, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism. 2004;53(12):1574–9.CrossRef Eid HMA, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism. 2004;53(12):1574–9.CrossRef
25.
Zurück zum Zitat Wang J, Sim AS, Wang XL, Salonikas C, Naidoo D, Wilcken DEL. Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease. Atherosclerosis. 2006;184(2):383–8.CrossRef Wang J, Sim AS, Wang XL, Salonikas C, Naidoo D, Wilcken DEL. Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease. Atherosclerosis. 2006;184(2):383–8.CrossRef
26.
Zurück zum Zitat Ribeiro Cavalari EM, de Paula MP, Arruda M, et al. Non-functioning adrenal incidentaloma: a novel predictive factor for metabolic syndrome. Clin Endocrinol (Oxf). 2018;89(5):586–95.CrossRef Ribeiro Cavalari EM, de Paula MP, Arruda M, et al. Non-functioning adrenal incidentaloma: a novel predictive factor for metabolic syndrome. Clin Endocrinol (Oxf). 2018;89(5):586–95.CrossRef
27.
Zurück zum Zitat Taya M, Paroder V, Bellin E, Haramati LB. The relationship between adrenal incidentalomas and mortality risk. Eur Radiol. 2019;29(11):6245–55.CrossRef Taya M, Paroder V, Bellin E, Haramati LB. The relationship between adrenal incidentalomas and mortality risk. Eur Radiol. 2019;29(11):6245–55.CrossRef
28.
Zurück zum Zitat Erbil Y, Ozbey N, Barbaros U, Unalp HR, SalmaslIoglu A, Özarmagan S. Cardiovascular risk in patients with nonfunctional adrenal incidentaloma: myth or reality? World J Surg. 2009;33(10):2099–105.CrossRef Erbil Y, Ozbey N, Barbaros U, Unalp HR, SalmaslIoglu A, Özarmagan S. Cardiovascular risk in patients with nonfunctional adrenal incidentaloma: myth or reality? World J Surg. 2009;33(10):2099–105.CrossRef
29.
Zurück zum Zitat Sokmen G, Sahin M, Tuzun D, et al. Assessment of subclinical cardiac alterations and atrial electromechanical delay by tissue doppler echocardiography in patients with non-functioning adrenal incidentaloma. Arq Bras Cardiol. 2018;111(5):656–63.PubMedPubMedCentral Sokmen G, Sahin M, Tuzun D, et al. Assessment of subclinical cardiac alterations and atrial electromechanical delay by tissue doppler echocardiography in patients with non-functioning adrenal incidentaloma. Arq Bras Cardiol. 2018;111(5):656–63.PubMedPubMedCentral
30.
Zurück zum Zitat Evran M, Akkuş G, Bozdoğan İB, et al. Carotid intima-media thickness as the cardiometabolic risk indicator in patients with nonfunctional adrenal mass and metabolic syndrome screening. Med Sci Monit. 2016;22:991–7.CrossRef Evran M, Akkuş G, Bozdoğan İB, et al. Carotid intima-media thickness as the cardiometabolic risk indicator in patients with nonfunctional adrenal mass and metabolic syndrome screening. Med Sci Monit. 2016;22:991–7.CrossRef
31.
Zurück zum Zitat Imga NN, Elalmıs OU, Tuna MM, et al. Comparison of echocardiographic findings in patients with non-functioning adrenal incidentalomas. Kaohsiung J Med Sci. 2017;33(6):295–301.CrossRef Imga NN, Elalmıs OU, Tuna MM, et al. Comparison of echocardiographic findings in patients with non-functioning adrenal incidentalomas. Kaohsiung J Med Sci. 2017;33(6):295–301.CrossRef
32.
Zurück zum Zitat Akkan T, Altay M, Ünsal Y, Dağdeviren M, Beyan E. Nonfunctioning adrenal incidentaloma affecting central blood pressure and arterial stiffness parameters. Endocrine. 2017;58(3):513–20.CrossRef Akkan T, Altay M, Ünsal Y, Dağdeviren M, Beyan E. Nonfunctioning adrenal incidentaloma affecting central blood pressure and arterial stiffness parameters. Endocrine. 2017;58(3):513–20.CrossRef
33.
Zurück zum Zitat Emral R, Aydoğan Bİ, Köse AD, Demir Ö, Çorapçıoğlu D. Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and metabolic syndrome. Endocrinol Diabetes Nutr (Engl Ed). 2019;66(7):402–9. Emral R, Aydoğan Bİ, Köse AD, Demir Ö, Çorapçıoğlu D. Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and metabolic syndrome. Endocrinol Diabetes Nutr (Engl Ed). 2019;66(7):402–9.
34.
Zurück zum Zitat Cansu GB, Sari R, Yilmaz N, Özdem S, Çubuk M. Markers of subclinical cardiovascular disease in nonfunctional adrenal incidentaloma patients without traditional cardiovascular risk factors. Exp Clin Endocrinol Diabetes. 2017;125(1):57–63.PubMed Cansu GB, Sari R, Yilmaz N, Özdem S, Çubuk M. Markers of subclinical cardiovascular disease in nonfunctional adrenal incidentaloma patients without traditional cardiovascular risk factors. Exp Clin Endocrinol Diabetes. 2017;125(1):57–63.PubMed
35.
Zurück zum Zitat Sydney GI, Ioakim KJ, Paschou SA. Insulin resistance and adrenal incidentalomas: a bidirectional relationship. Maturitas. 2019;121:1–6.CrossRef Sydney GI, Ioakim KJ, Paschou SA. Insulin resistance and adrenal incidentalomas: a bidirectional relationship. Maturitas. 2019;121:1–6.CrossRef
36.
Zurück zum Zitat Akkus G, Evran M, Sert M, Tetiker T. Adipocytokines in non-functional adrenal Incidentalomas and relation with insulin resistance parameters. Endocr Metab Immune Disord Drug Targets. 2018;19(3):326–32.CrossRef Akkus G, Evran M, Sert M, Tetiker T. Adipocytokines in non-functional adrenal Incidentalomas and relation with insulin resistance parameters. Endocr Metab Immune Disord Drug Targets. 2018;19(3):326–32.CrossRef
Metadaten
Titel
Non-functioning adrenal incidentalomas may increase toxic metabolites
verfasst von
Assis. Prof. Irfan Karahan, M.D.
Prof. Senay Durmaz Ceylan, M.D.
Assoc. Prof. Askin Gungunes, M.D.
Assoc. Prof. Aydın Cifci, M.D.
Fatih Eker, M.D.
Prof. Ucler Kisa, M.D.
Publikationsdatum
13.07.2021
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 3-4/2022
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-021-01909-9

Weitere Artikel der Ausgabe 3-4/2022

Wiener klinische Wochenschrift 3-4/2022 Zur Ausgabe

MUW researcher of the month

MUW researcher of the month