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Circadian rhythm of salivary cortisol in infants with congenital heart disease

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Abstract

Children with congenital heart disease (CHD) have associated extracardiac co-morbidities at the time of surgery and during ongoing growth and development. Perioperative events include disrupted glucose homeostasis, capillary leak, and fluid retention. The hypothalamic–pituitary–adrenal (HPA) axis has an important role in homeostasis in that the secretion of cortisol contributes to the response to stress, glucose regulation, blood volume control, and immune regulation. We investigated the diurnal rhythm of the HPA axis in infants with CHD by measuring salivary cortisol in the morning (0600–0900 h—circadian peak) and evening (2100–2400 h—circadian nadir). Twenty-nine infants aged 12 weeks to 1 year were included: 16 with acyanotic disease (SpO2 ≥ 90 %) and 13 with cyanotic disease (SpO2 < 90 %). Morning salivary cortisol was similar between the two groups [acyanotic 7.0 nmol/L (1.8–23.1); cyanotic 9.7 nmol/L (0.9–15.6); p = 0.68]. Evening salivary cortisol was similar between the two groups [acyanotic 0.9 nmol/L (0.2–8.5); cyanotic 1.4 nmol/L (0.5–14.9); p = 0.32]. Both cyanotic and acyanotic groups demonstrated an intact diurnal rhythm. In conclusion, chronic hypoxia secondary to cyanotic CHD does not affect the circadian rhythm of the HPA axis. By 12  weeks of age, infants with hypoxia secondary to cyanotic CHD have a normal cortisol diurnal rhythm.

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References

  1. J.I. Hoffman, S. Kaplan, The incidence of congenital heart disease. J. Am. Coll. Cardiol. 39(12), 1890–1900 (2002)

    Article  PubMed  Google Scholar 

  2. Y. Hamada, K. Kawachi, N. Tsunooka, Y. Nakamura, S. Takano, H. Imagawa, Capillary leakage in cardiac surgery with cardiopulmonary bypass. Asian Cardiovasc Thorac Ann 12(3), 193–197 (2004)

    PubMed  Google Scholar 

  3. R.S. Boneva, L.D. Botto, C.A. Moore, Q. Yang, A. Correa, J.D. Erickson, Mortality associated with congenital heart defects in the United States: trends and racial disparities. Circulation 103(19), 2376–2381 (2001)

    Article  PubMed  CAS  Google Scholar 

  4. R.H. Feldt, J.C. Ewert, G.B. Stickler, W.H. Weidman, Children with congenital heart disease. Motor development, intelligence. Am. J. Dis. Child. 117(3), 281–287 (1969)

    PubMed  CAS  Google Scholar 

  5. A. Silbert, P.H. Wolff, B. Mayer, A. Rosenthal, A.S. Nadas, Cyanotic heart disease, psychological development. Pediatrics 43(2), 192–200 (1969)

    PubMed  CAS  Google Scholar 

  6. R.B. Aisenberg, A. Rosenthal, A.S. Nadas, P.H. Wolff, Developmental delay in infants with congenital heart disease. Correlation with hypoxemia and congestive heart failure. Pediatr. Cardiol. 3(2), 133–137 (1982)

    Article  PubMed  CAS  Google Scholar 

  7. C. Samango-Sprouse, E.C. Suddaby, Developmental concerns in children with congenital heart disease. Curr. Opin. Cardiol. 12(1), 91–98 (1997)

    Article  PubMed  CAS  Google Scholar 

  8. T. Kodama, N. Shimizu, N. Yoshikawa et al., Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene expression. J. Biol. Chem. 278(35), 33384–33391 (2003)

    Article  PubMed  CAS  Google Scholar 

  9. S. Kliegman et al., Nelson Textbook of pediatrics, 18th edn. (Saunders Elsevier, Philadelphia, 2007), pp. 2352–2353

    Google Scholar 

  10. E.D. Bruder, J.K. Taylor, K.J. Kamer, H. Raff, Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295(4), R1195–R1203 (2008)

    Article  PubMed  CAS  Google Scholar 

  11. H. Raff, J.J. Lee, E.P. Widmaier, M.K. Oaks, W.C. Engeland, Basal and adrenocorticotropin-stimulated corticosterone in the neonatal rat exposed to hypoxia from birth: modulation by chemical sympathectomy. Endocrinology 145(1), 79–86 (2004)

    Article  PubMed  CAS  Google Scholar 

  12. K. Fujimori, A. Takanashi, C. Endo, A. Sato, Stress hormone responses during 24-hour hypoxemia in preterm goat fetus. Tohoku J. Exp. Med. 215(2), 189–197 (2008)

    Article  PubMed  CAS  Google Scholar 

  13. H. Raff, L. Jacobson, W.E. Cullinan, Augmented hypothalamic corticotrophin-releasing hormone mRNA, corticosterone responses to stress in adult rats exposed to perinatal hypoxia. J. Neuroendocrinol. 19(11), 907–912 (2007)

    Article  PubMed  CAS  Google Scholar 

  14. H. Raff, L. Jacobson, W.E. Cullinan, Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285(5), R1224–R1230 (2003)

    PubMed  CAS  Google Scholar 

  15. D. Zayour, S.T. Azar, N. Azar et al., Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease. Endocr. Res. 29(2), 191–200 (2003)

    Article  PubMed  CAS  Google Scholar 

  16. L.B. Santiago, S.M. Jorge, A.C. Moreira, Longitudinal evaluation of the development of salivary cortisol circadian rhythm in infancy. Clin. Endocrinol. (Oxf). 44(2), 157–161 (1996)

    Article  CAS  Google Scholar 

  17. W.S. Gozansky, J.S. Lynn, M.L. Laudenslager, W.M. Kohrt, Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic–pituitary–adrenal axis activity. Clin. Endocrinol. (Oxf). 63(3), 336–341 (2005)

    Article  CAS  Google Scholar 

  18. H. Raff, Salivary cortisol and the diagnosis of Cushing’s syndrome: a coming of age. Endocrine 41(3), 353–354 (2012)

    Article  PubMed  CAS  Google Scholar 

  19. Z.E. Belaya, A.V. Iljin, G.A. Melnichenko et al., Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing’s syndrome. Endocrine 41(3), 494–500 (2012)

    Article  PubMed  CAS  Google Scholar 

  20. C. de Weerth, J. Jansen, M.H. Vos, I. Maitimu, E.G. Lentjes, A new device for collecting saliva for cortisol determination. Psychoneuroendocrinology 32(8–10), 1144–1148 (2007)

    Article  PubMed  Google Scholar 

  21. H. Raff, P.J. Homar, D.P. Skoner, New enzyme immunoassay for salivary cortisol. Clin. Chem. 49(1), 203–204 (2003)

    Article  PubMed  CAS  Google Scholar 

  22. K.J. Jenkins, K. Gauvreau, J.W. Newburger, T.L. Spray, J.H. Moller, L.I. Iezzoni, Consensus-based method for risk adjustment for surgery for congenital heart disease. J. Thorac. Cardiovasc. Surg. 123(1), 110–118 (2002)

    Article  PubMed  Google Scholar 

  23. H. Raff, J.L. Raff, J.W. Findling, Late-night salivary cortisol as a screening test for Cushing’s syndrome. J. Clin. Endocrinol. Metab. 83(8), 2681–2686 (1998)

    Article  PubMed  CAS  Google Scholar 

  24. F.A. Scheer, B. Van Paassen, G.A. Van Montfrans et al., Human basal cortisol levels are increased in hospital compared to home setting. Neurosci. Lett. 333(2), 79–82 (2002)

    Article  PubMed  CAS  Google Scholar 

  25. K.R. Plumpton, B.J. Anderson, J. Beca, Thyroid hormone and cortisol concentrations after congenital heart surgery in infants younger than 3 months of age. Intensive Care Med. 36(2), 321–328 (2010)

    Article  PubMed  CAS  Google Scholar 

  26. H. Raff, J. Shinsako, L.C. Keil, M.F. Dallman, Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs. Am. J. Physiol. 244(5), E453–E458 (1983)

    PubMed  CAS  Google Scholar 

  27. R.W. Jones, J.H. Baumer, M.C. Joseph, E.A. Shinebourne, Arterial oxygen tension and response to oxygen breathing in differential diagnosis of congenital heart disease in infancy. Arch. Dis. Child. 51(9), 667–673 (1976)

    Article  PubMed  CAS  Google Scholar 

  28. H.J. Schmitt, W.H. Schuetz, P.A. Proeschel, C. Jaklin, Accuracy of pulse oximetry in children with cyanotic congenital heart disease. J. Cardiothorac. Vasc. Anesth. 7(1), 61–65 (1993)

    Article  PubMed  CAS  Google Scholar 

  29. F. Moncloa, E. Pretell, Cortisol secretion rate, ACTH and methopyrapone tests in high altitude native residents. J. Clin. Endocrinol. Metab. 24, 915–918 (1964)

    Article  PubMed  CAS  Google Scholar 

  30. F. Moncloa, J. Donayre, L.A. Sobrevilla, R. Guerra-García, Endocrine studies at high altitude II Adrenal cortical function in sea level natives exposed to high altitudes (4300 meters for 2 weeks. J. Clin. Endocrinol. Metab. 25(12), 1640–1642 (1965)

    Article  PubMed  CAS  Google Scholar 

  31. J.J. Larsen, J.M. Hansen, N.V. Olsen, H. Galbo, F. Dela, The effect of altitude hypoxia on glucose homeostasis in men. J. Physiol. 504(Pt 1), 241–249 (1997)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank the Herma Heart Center at the Children’s Hospital of Wisconsin; Jane Lee MD, Martin Wakeham MD, Karen Marcdante MD, Mary Dahmer, PhD, Mary Kasch, and Sara Rademacher at the Medical College of Wisconsin; and Peter Homar and the Endocrine Research Laboratory at the Aurora St. Luke’s Medical Center. The authors also thank the Elaine Kohler Fund and the Aurora Health Care Patient-Centered Research.

Conflict of interest

The authors of this study report no conflict of interest.

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Authors and Affiliations

  1. Division of Pediatric Critical Care, Medical College of Wisconsin, 9000 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA

    Giovanna Caprirolo, Nancy S. Ghanayem & Kathy Murkowski

  2. Section of Quantitative Health Science, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Melodee L. Nugent & Pippa M. Simpson

  3. Endocrine Research Laboratory, Aurora St. Luke’s Medical Center, 2801 W KK River Pky Suite 245, Milwaukee, WI, 53215, USA

    Hershel Raff

  4. Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    Nancy S. Ghanayem

  5. Department of Medicine, Surgery and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Hershel Raff

  6. Division of Pediatric Critical Care, 414 N. 9th St. Suite 4W64, Springfield, IL, 62769, USA

    Giovanna Caprirolo

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  1. Giovanna Caprirolo
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  2. Nancy S. Ghanayem
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Correspondence to Giovanna Caprirolo.

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Caprirolo, G., Ghanayem, N.S., Murkowski, K. et al. Circadian rhythm of salivary cortisol in infants with congenital heart disease. Endocrine 43, 214–218 (2013). https://doi.org/10.1007/s12020-012-9791-z

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  • DOI: https://doi.org/10.1007/s12020-012-9791-z

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