PDF herunterladen
Horm Metab Res 2020; 52(09): 654-659
DOI: 10.1055/a-1116-2173
Endocrine Care

Serum Fetuin-A and Insulin Levels in Classic Congenital Adrenal Hyperplasia

Erdal Kurnaz
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
,
Semra Çetinkaya
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
,
Şervan Özalkak
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
,
Elvan Bayramoğlu
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
,
Gülşah Demirci
2   Department of Medical Biochemistry, Ankara University Medical Faculty, Ankara, Turkey
,
Hasan Serdar Öztürk
2   Department of Medical Biochemistry, Ankara University Medical Faculty, Ankara, Turkey
,
Şenay Savaş Erdeve
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
,
Zehra Aycan
1   Pediatric Endocrinology Clinic, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R2=42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients.

Key words

congenital adrenal hyperplasia - fetuin-A - alpha-2-HS-glycoprotein - insulin resistance


Publikationsverlauf

Eingereicht: 17. Oktober 2019

Angenommen: 05. Februar 2020

Artikel online veröffentlicht:
27. Februar 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Mnif MF, Kamoun M, Mnif F. et al. Metabolic profile and cardiovascular risk factors in adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Indian J Endocrinol Metab 2012; 16: 939-946
    CrossrefPubMedSuche in Google Scholar
  • 2 Finkielstain GP, Kim MS, Sinaii N. et al. Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2012; 97: 4429-4438
    CrossrefPubMedSuche in Google Scholar
  • 3 Kim MS, Dao-Tran A, Davidowitz E. et al. Carotid intima-media thickness is associated with increased androgens in adolescents and young adults with classical congenital adrenal hyperplasia. Horm Res Paediatr 2016; 85: 242-249
    CrossrefPubMedSuche in Google Scholar
  • 4 van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options?. Eur J Clin Invest 2009; 39: 81-93
    CrossrefPubMedSuche in Google Scholar
  • 5 Wöltje M, Tschöke B, von Bülow V. et al. CCAAT enhancer binding protein beta and hepatocyte nuclear factor 3beta are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression. J Mol Endocrinol 2006; 36: 261-277
    CrossrefPubMedSuche in Google Scholar
  • 6 Voelkl J, Pakladok T, Lin Y. et al. Up-regulation of hepatic alpha-2-HS-glycoprotein transcription by testosterone via androgen receptor activation. Cell Physiol Biochem 2014; 33: 1911-1920
    CrossrefPubMedSuche in Google Scholar
  • 7 Harada N, Yoda Y, Yotsumoto Y. et al. Androgen signaling expands beta-cell mass in male rats and beta-cell androgen receptor is degraded under high-glucose conditions. Am J Physiol Endocrinol Metab 2018; 314: E274-E286
    CrossrefPubMedSuche in Google Scholar
  • 8 Reinehr T, Karges B, Meissner T. et al. Fibroblast growth factor 21 and Fetuin-A in obese adolescents with and without type 2 diabetes. J Clin Endocrinol Metab 2015; 100: 3004-3010
    CrossrefPubMedSuche in Google Scholar
  • 9 Kalabay L, Chavin K, Lebreton JP. et al. Human recombinant alpha 2-HS glycoprotein is produced in insect cells as a full length inhibitor of the insulin receptor tyrosine kinase. Horm Metab Res 1998; 30: 1-6
    Thieme ConnectPubMedSuche in Google Scholar
  • 10 Mathews ST, Singh GP, Ranalletta M. et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes. 2002; 51: 2450-2458
    CrossrefPubMedSuche in Google Scholar
  • 11 Goustin AS, Abou-Samra AB. The “thrifty” gene encoding Ahsg/Fetuin-A meets the insulin receptor: Insights into the mechanism of insulin resistance. Cell Signal. 2011; 23: 980-990
    CrossrefPubMedSuche in Google Scholar
  • 12 Neyzi O, Bundak R, Gokcay G. et al. Reference values for weight, height, head circumference, and body mass index in Turkish Children. J Clin Res Pediatr Endocrinol 2015; 7: 280-293
    CrossrefPubMedSuche in Google Scholar
  • 13 Flynn JT, Kaelber DC, Baker-Smith CM. et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017; 140: e20171904
    Suche in Google Scholar
  • 14 Tanner JM. Growth and maturation during adolescence. Nutrition reviews 1981; 39: 43-55
    CrossrefPubMedSuche in Google Scholar
  • 15 Kurtoglu S, Hatipoglu N, Mazicioglu M. et al. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol 2010; 2: 100-106
    CrossrefPubMedSuche in Google Scholar
  • 16 Expert Panel on Integrated Guidelines for Cardiovascular H, Risk Reduction in C, Adolescents, National Heart L, Blood I Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011; 128 (Suppl. 05) S213-S256
    CrossrefPubMedSuche in Google Scholar
  • 17 Dunaif A, Graf M, Mandeli J. et al. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65: 499-507
    CrossrefPubMedSuche in Google Scholar
  • 18 Chang RJ, Nakamura RM, Judd HL. et al. Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab 1983; 57: 356-359
    CrossrefPubMedSuche in Google Scholar
  • 19 Taylor SI, Dons RF, Hernandez E. et al. Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor. Ann Intern Med 1982; 97: 851-855
    CrossrefPubMedSuche in Google Scholar
  • 20 Celik N, Alp H, Camtosun E. et al. The association between premature adrenarche and cardiovascular risk may be greater than expected. Horm Res Paediatr 2017; 87: 7-14
    CrossrefPubMedSuche in Google Scholar
  • 21 Mori K, Emoto M, Araki T. et al. Association of serum fetuin-A with carotid arterial stiffness. Clin Endocrinol 2007; 66: 246-250
    CrossrefPubMedSuche in Google Scholar
  • 22 Ariyawatkul K, Tepmongkol S, Aroonparkmongkol S. et al. Cardio-metabolic risk factors in youth with classical 21-hydroxylase deficiency. Eur J Pediatr 2017; 176: 537-545
    CrossrefPubMedSuche in Google Scholar
  • 23 Mooij CF, van Herwaarden AE, Sweep F. et al. Cardiovascular and metabolic risk in pediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency. J Pediatr Endocrinol Metab 2017; 30: 957-966
    CrossrefPubMedSuche in Google Scholar
  • 24 Harrington J, Pena AS, Gent R. et al. Adolescents with congenital adrenal hyperplasia because of 21-hydroxylase deficiency have vascular dysfunction. Clin Endocrinol 2012; 76: 837-842
    CrossrefPubMedSuche in Google Scholar
  • 25 Williams RM, Deeb A, Ong KK. et al. Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia. Clin Endocrinol 2010; 72: 155-160
    CrossrefPubMedSuche in Google Scholar
  • 26 Arlt W, Willis DS, Wild SH. et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab 2010; 95: 5110-5121
    CrossrefPubMedSuche in Google Scholar
  • 27 Botero D, Arango A, Danon M. et al. Lipid profile in congenital adrenal hyperplasia. Metabolism 2000; 49: 790-793
    CrossrefPubMedSuche in Google Scholar