Adipocytokines in Non-functional Adrenal Incidentalomas and Relation with Insulin Resistance Parameters

Author(s): Gamze Akkus*, Mehtap Evran, Murat Sert, Tamer Tetiker.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets

Volume 19 , Issue 3 , 2019

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Abstract:

Objective: Adrenal incidentalomas are diagnosed incidentally during radiological screenings and require endocrinological investigations for hormonal activity and malignancy. In certain studies, it has been reported that non-functional incidentalomas can be associated with high adipocytokines levels affecting the insulin resistance just like the adipose tissue with metabolic syndrome. Here, we studied serum adipocytokine levels including leptin, resistin, visfatin, omentin 1 and adiponectin in subjects with non-functional adrenal incidentaloma.

Methods: Seventy-seven (77) patients (Female 57; Male 20) with non-functional adrenal incidentaloma (NFAI) were enrolled in the study. All patients’ past medical history, physical examination including Body Mass Index (BMI) and waist circumference were performed. The patients’ demographic, radiologic, hormonal and biochemical parameters were recorded. To compare the parameters, a control group (CG) (n=30) was formed from healthy volunteers. Both groups were matched for age, gender, waist circumference and BMI. Serum adipocytokines including leptin, resistin, visfatin, omentin 1 and adiponectin were measured quantitatively by ELISA. Fasting plasma glucose, insulin, sodium, potassium, cortisol, adrenocorticotropic hormone (ACTH), lipid profiles, and dehidroepiandrostenedion sulphate (DHEAS) were measured.

Results: Mean age of the patients was 52.2±10.4 years. BMI and waist circumference of NFAI patients were 26.2±3.28 kg/m2 and 90.2 ±7.5cm, respectively. The mean age of the control group was 48.0±8.16. BMI and waist circumference values for the control group were 25.3±3.5 kg/m2 and 88.3±9.6 cm, respectively. When both groups were compared for age, gender, BMI and waist circumference were non-significant (p>0.05). Serum fasting insulin, total cholesterol, LDL, triglyceride levels of the NFAI group were significantly higher than CG (p<0.05). The insulin resistance index (HOMAIR) values of the NFAI subjects were found to be higher than CG (2.5±1.37, 1.1±0.3 p=0.00). Resistin level of NFAI group was also found to be higher than CG [286.6 ng/L vs. 197 ng/L; (P=0,00)], respectively. Leptin levels of NFAI were significantly higher than CG [441.1 ng/mL vs. 186.5 ng/mL; (P=0.00)] respectively. Adiponectin levels were significantly reduced in the NFAI group than in the CG [10.7 mg/L vs. 30.8 mg/L; (P=0.00)]. Comparision of visfatin and omentin levels was nonsignificant.

Conclusion: In this study on subjects with non-functional adrenal incidentaloma, we found not only significantly decreased serum adiponectin levels but also increased leptin, resistin levels as well as dyslipidemia, hypertension and high insulin resistance index. All of which could affect insulin resistance and cardiovascular risk factors. The underlying mechanisms of these findings are unknown, hence further studies are needed.

Keywords: Adrenal incidentaloma, leptin, resistin, visfatin, omentin, adipocytokine, insulin resistance.

[1]
Terzolo, M.; Bovio, S.; Pia, A.; Reimondo, G.; Angeli, A. Management of adrenal incidentaloma. Best Pract. Res. Clin. Endocrinol. Metab., 2009, 23, 233-243.
[2]
Mantero, F.; Terzolo, M.; Arnaldi, G.; Osella, G.; Masini, A.M.; Alì, A.; Giovagnetti, M.; Opocher, G.; Angeli, A. A survey on adrenal incidentaloma in Italy. J. Clin. Endocrinol. Metab., 2000, 85, 637-644.
[3]
Arduc, A.; Isik, S.; Ozuguz, U.; Tutuncu, Y.A.; Kucukler, F.K.; Ozcan, H.N.; Berker, D.; Guler, S. Relationship between thyroid nodules and non-functioning adrenal incidentalomas and their association with insulin resistance. Endocr. Res., 2014, 39, 99-104.
[4]
Evran, M.; Akkus, G.; Berk Bozdoğan, İ.; Deniz, A.; Gok, M.; Deniz, A.; Sert, M.; Tetiker, T. Carotid intima-media thickness as the cardiometabolic risk indicator in patients with nonfunctional adrenal mass and metabolic syndrome screening. Med. Sci. Monit., 2015, 22, 991-997.
[5]
Peppa, M.; Boutati, E.; Koliaki, C.; Garoflos, E.; Raptis, S.A. Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal incidentalomas: A cause-effect relationship? Metabolism, 2010, 59, 1435-1441.
[6]
Alberti, K.G.; Eckel, R.H.; Grundy, S.M. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Circulation, 2009, 120, 1640-1645.
[7]
Cardinali, D.P.; Hardeland, R. Inflammaging, metabolic syndrome and melatonin: A call for treatment studies. Neuroendocrinology, 2016, 5, 11.
[8]
Norata, G.D.; Ongari, M.; Garlaschelli, K.; Raselli, S.; Grigore, L.; Catapano, A.L. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur. J. Endocrinol., 2007, 156, 279-284.
[9]
Maury, E.; Brichard, S.M. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol. Cell. Endocrinol., 2010, 314, 1-16.
[10]
Campanati, A.; Ganzetti, G.; Maurizio, M. Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-α inhibitors: results of a retrospective analysis. Int. J. Dermatol., 2015, 54, 839-845.
[11]
Landeros-Olvera, E.; López-Alvarenga, J.C.; Nava-González, E.J.; Gallegos-Cabriales, E.; Lavalle-González, F.; Bastarrachea, R.A.; Salazar González, B.C. Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha. Arch. Cardiol., 2014, 84, 177-182.
[12]
Yang, R.Z.; Lee, M.J.; Hu, H. Identification of omentin as a novel depot-specificadipokine in human adipose tissue: possible role in modulating insulin action. Am. J. Physiol. Endocrinol. Metab., 2006, 290(6), E1253-E1261.
[13]
Narumi, T.; Watanabe, T.; Kadowaki, S.; Kinoshita, D.; Yokoyama, M.; Honda, Y. Otaki. Y.; Nishiyama. S.; Takahashi. H.; Arimoto. T.; Shishido. T.; Miyamoto. T.; Kubota. I. Impact of serum omentin-1 levels on cardiac prognosis in patients with heart failure. Cardiovasc. Diabetol., 2014, 13, 84.
[14]
Androulakis, I.I.; Kaltsas, G.A.; Kollias, G.E.; Markou, A.C.; Gouli, A.K.; Thomas, D.A.; Alexandraki, K.I.; Papamichael, C.M.; Hadjidakis, D.J.; Piaditis, G.P. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J. Clin. Endocrinol. Metab., 2014, 99, 2754-2762.
[15]
Garrapa, G.G.; Pantanetti, P.; Arnaldi, G.; Mantero, F.; Faloia, E. Body composition and metabolic features in women with adrenal incidentaloma or Cushing’s syndrome. J. Clin. Endocrinol. Metab., 2001, 86, 5301-6306.
[16]
McTernan, C.L.; McTernan, P.G.; Harte, A.L.; Levick, P.; Barnett, A.; Kumar, S. Resistin, central obesity, and type 2 diabetes. Lancet, 2002, 359, 46-47.
[17]
Wittenbecher, C.; di Giuseppe, R.; Biemann, R.; Menzel, J.; Arregui, M.; Hoffmann, J.; Aleksandrova, K.; Boeing, H.; Isermann, B.; Schulze, M.B.; Weikert, C. Reproducibility of retinol binding protein 4 and omentin-1 measurements over a four months period: A reliability study in a cohort of 207 apparently healthy participants. PLoS One, 2015, 10, e0138480.
[18]
Masquio, D.C.; Pian-Ganen, A.; Oyama, L.M.; Campos, R.M.; Santamarina, A.B.; de Souza, G.I.; Gomes, A.D.; Moreira, R.G.; Corgosinho, F.C.; do Nascimento, C.M.; Tock, L.; Tufik, S.; de Mello, M.T.; Dâmaso, A.R. The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy. J. Nutr. Biochem., 2016, 33, 136-144.
[19]
D’souza, A.M.; Asadi, A.; Johnson, J.D.; Covey, S.D.; Kieffer, T.J. Leptin deficiency in rats results in hyperinsulinemia and impaired glucose homeostasis. Endocrinology, 2014, 155, 1268-1279.
[20]
Woodward, L.; Akoumionakis, I.; Antonioades, C. Unravelling the adiponectin paradox: novel roles of adiponectin in the regulation of cardiovascular disease. Br. J. Pharmacol., 2017, 174(22), 4007-4020.
[21]
Fukuhara, A.; Matsuda, M.; Nishizawa, M.; Segawa, K.; Tanaka, M.; Kishimoto, K.; Matsuki, Y.; Murakami, M.; Ichisaka, T.; Murakami, H.; Watanabe, E.; Takagi, T.; Akiyoshi, M.; Ohtsubo, T.; Kihara, S.; Yamashita, S.; Makishima, M.; Funahashi, T.; Yamanaka, S.; Hiramatsu, R.; Matsuzawa, Y.; Shimomura, I. Visfatin1 A protein secreted by visceral fat that mimics the effects of insulin. Science, 2005, 307, 426-430.
[22]
Gradidge, P.; Norris, S.; Jaff, N.G. Metabolic and body composition risk factors associated with metabolic syndrome in a cohort of women with a high prevalence of cardiometabolic disease. PLoS One, 2016, 11(9), e0162247.
[23]
Wolk, K.; Sabat, R. Adipokines in psoriasis: An important link between skin inflammation and metabolic alterations. Rev. Endocr. Metab. Disord., 2016, 23, 1-13.
[24]
Mirfeizi, Z.; Noubacht, Z.; Rezaie, A.E.; Jokar, M.H.; Sarabi, Z.S. Plasma levels of leptin and visfatin in rheumatoid arthritis patients; is there any relationship with joint damage? Iran. J. Basic Med. Sci., 2014, 17, 662-666.
[25]
Masserini, B.; Morelli, V.; Palmieri, S.; Eller-Vaicinicher, C.; Zhuokuskaya, V.; Cairoli, E.; Orsi, E.; Beck-Peccoz, P.; Spada, A.; Chiodini, I. Lipid abnormalities in patients with adrenal incidentalomas: role of subclinical hypercortisolism and impaired glucose metabolism. J. Endocrinol. Invest., 2015, 38, 623-628.
[26]
Preogamvros, I.; Vassiliadi, D.A.; Karapanou, O.; Botoulo, E.; Tzanela, M.; Tsagarakis, S. Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas. Eur. J. Endocrinol., 2016, 173, 719-725.
[27]
Muscogiuri, G.; Colao, A.; Orio, F. Insulin-mediated diseases: Adrenal mass and polycystic ovary syndrome. Trends Endocrinol. Metab., 2015, 26, 512-514.
[28]
Ermetici, F.; Malavazos, A.E.; Corbetta, S.; Morricone, L.; Corsi, M.M.; Ambrosi, B. Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. Metabolism, 2007, 56, 686-692.
[29]
Tuna, M.M.; Imga, N.N.; Dogan, B.; Yılmaz, F.M.; Topçuoğlu, C.; Akbaba, G.; Berker, D.; Güler, S. Non-functioning adrenal incidentalomas are associated with higher hypertension prevalence and higher risk of atherosclerosis. J. Endocrinol. Invest., 2014, 37, 765-768.
[30]
Lazurova, I.; Spisakova, D.; Wagnerova, H. Clinically silent adrenal adenomas - their relation to the metabolic syndrome and to GNB3 C825T gene polymorphism. Wien. Klin. Wochenschr., 2011, 123, 618-622.
[31]
Unal, A.; Aytürk, S.; Aldemir, D. Serum adiponectin level as a predictor of subclinical Cushing’s syndrome in patients with adrenal incidentaloma. Int. J. Endocrinol., 2016, 2016, 8519362.


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Article Details

VOLUME: 19
ISSUE: 3
Year: 2019
Page: [326 - 332]
Pages: 7
DOI: 10.2174/1871530318666181009112042
Price: $58

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