Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-24T05:46:34.585Z Has data issue: false hasContentIssue false
  • English
  • Français

Low serum 25-hydroxyvitamin D levels and secondary hyperparathyroidism in Fontan patients

Published online by Cambridge University Press:  17 August 2015

Finn Holler ,
Tobias Hannes ,
Ingo Germund ,
Mathias Emmel ,
Heike Hoyer-Kuhn ,
Markus Khalil ,
Narayanswami Sreeram  and
Floris E. A. Udink ten Cate
Finn Holler
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
Tobias Hannes
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
Ingo Germund
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
Mathias Emmel
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
Heike Hoyer-Kuhn
Affiliation:
Department of Paediatrics, Children’s Hospital, University of Cologne, Cologne, Germany
Markus Khalil
Affiliation:
Paediatric Heart Centre, Justus-Liebig University, Giessen, Germany
Narayanswami Sreeram
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
Floris E. A. Udink ten Cate*
Affiliation:
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany
*
Correspondence to: Dr F. E. A. Udink ten Cate, Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpenerstrasse 62, 50973 Cologne, Germany. Tel: +492 214 783 2330; Fax: +492 214 783 2646; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Limited data exist on the vitamin D status in Fontan patients. We determined the prevalence and potential risk factors of vitamin D deficiency in this patient subset.

Methods and results

Data were collected from 27 Fontan patients (55.6% male, mean age 8.1±5.3 years). Protein-losing enteropathy was diagnosed in six patients (22.2%). Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level of <20 ng/ml. The neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, was calculated. Associations between laboratory measurements and patient characteristics were explored. Mean serum 25-hydroxyvitamin D level was 14.1±10.4 ng/ml. Vitamin D deficiency was found in 19/27 patients (70.3%). Only skin type was associated with vitamin D deficiency (p=0.04). Hyperparathyroidism was present in 5/21 (23.8%) patients, and was more prevalent in patients with protein-losing enteropathy (p<0.001). Parathyroid hormone levels correlated with parameters of systemic inflammation (neutrophil-to-lymphocyte ratio: r=0.484, p=0.026; relative lymphocyte count: r=−0.635, p=0.002). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D levels (p<0.0001), and was accompanied by a reduction in parathyroid hormone concentrations (p=0.032).

Conclusions

A high prevalence of vitamin D deficiency was found among Fontan patients, independent of age, time after Fontan procedure, ventricular morphology, and presence of protein-losing enteropathy. A potentially important link between parathyroid hormone levels and systemic inflammation is suggested.

Keywords

Fontanprotein-losing enteropathy25-hydroxyvitamin Dvitamin D deficiencyparathyroid hormone
Type
Original Articles
Information
Cardiology in the Young , Volume 26 , Issue 5 , June 2016 , pp. 876 - 884
Check for updates
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

Both authors contributed equally.

References

1. Cetta, F, Feldt, RH, O’Leary, PW, et al. Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992. J Am Coll Cardiol 1996; 28: 480–486.Google Scholar
2. Gentles, TL, Mayer, JE Jr, Gauvreau, K, et al. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome. J Thorac Cardiovasc Surg 1997; 114: 376–391.Google Scholar
3. Gewillig, M, Goldberg, DJ. Failure of Fontan circulation. Heart Fail Clin 2014; 10: 105–116.CrossRefGoogle ScholarPubMed
4. Baek, JS, Bae, EJ, Ko, JS, et al. Late hepatic complications after Fontan operation: non-invasive markers of hepatic fibrosis and risk factors. Heart 2010; 96: 1750–1755.CrossRefGoogle ScholarPubMed
5. Mori, M, Aquirre, AJ, Elder, RW, et al. Beyond a broken heart: circulatory dysfunction in the failing Fontan. Pediatr Cardiol 2014; 35: 569–579.Google Scholar
6. Rychik, J, Goldberg, D, Rand, E, et al. End-organ consequences of the Fontan operation: liver fibrosis, protein-losing enteropathy and plastic bronchitis. Cardiol Young 2013; 23: 831–840.CrossRefGoogle ScholarPubMed
7. Avitabile, CM, Leonard, MB, Zemel, BS, et al. Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation. Heart 2014; 100: 1702–1707.Google Scholar
8. Bulut, OP, Romero, R, Mahle, WT, et al. Magnetic resonance imaging identifies unsuspected liver abnormalities in patients after the Fontan procedure. J Pediatr 2013; 163: 201–206.CrossRefGoogle ScholarPubMed
9. Giardini, A, Balducci, A, Specchia, S, Gargiulo, G, Bonvicini, M, Picchio, FM. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 2008; 29: 1681–1687.CrossRefGoogle ScholarPubMed
10. Thacker, D, Patel, A, Dodds, K, Goldberg, DJ, Semeao, E, Rychik, J. Use of oral budesonide in the management of protein-losing enteropathy after the Fontan operation. Ann Thorac Surg 2010; 89: 837–842.Google Scholar
11. Chin, AJ, Stephens, P, Goldmuntz, E, Leonard, MB. Serum alkaline phosphatase reflects post-Fontan hemodynamics in children. Pediatr Cardiol 2009; 30: 138–145.Google Scholar
12. Goldberg, DJ, Dodds, K, Avitabile, CM, et al. Children with protein-losing enteropathy after the Fontan operation are at risk for abnormal bone mineral density. Pediatr Cardiol 2012; 33: 1264–1268.Google Scholar
13. Kim, SJ, Park, IS, Song, JY, Lee, JY, Shim, WS. Reversal of protein-losing enteropathy with calcium replacement in a patient after Fontan operation. Ann Thorac Surg 2004; 77: 1456–1457.CrossRefGoogle Scholar
14. Holick, MF, Binkley, NC, Bischoff-Ferrari, HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96: 1911–1930.Google Scholar
15. Misra, M, Pacaud, D, Petryk, A, Collett-Solberg, PF, Kappy, M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 2008; 122: 398–417.CrossRefGoogle ScholarPubMed
16. Norman, PE, Powell, JT. Vitamin D and cardiovascular diseases. Circ Res 2014; 114: 379–393.Google Scholar
17. Beigelman, A, Zeiger, RS, Mauger, D, et al. The associations between vitamin D status and rate of exacerbations requiring oral corticosteroids in preschool children with recurrent wheezing. J Allergy Clin Immunol 2014; 133: 1489–1492.CrossRefGoogle ScholarPubMed
18. Huibers, MH, Visser, DH, Deckers, MM, van Schoor, NM, van Furth, AM, Wolf, BH. Vitamin D deficiency among native Dutch and first- and second-generation non-western immigrants. Eur J Pediatr 2014; 173: 583–588.Google Scholar
19. Kelly, A, Brooks, LJ, Dougherty, S, Carlow, DC, Zemel, BS. A cross-sectional study of vitamin D and insulin resistance in children. Arch Dis Child 2011; 96: 447–452.CrossRefGoogle ScholarPubMed
20. Lee, JH, O’Keefe, JH, Bell, D, Hensrud, DD, Holick, MF. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol 2008; 52: 1949–1956.Google Scholar
21. McNally, JD, Menon, K, Chakraborty, P, et al. The association of vitamin D status with pediatric critical illness. Pediatrics 2012; 130: 429–436.CrossRefGoogle ScholarPubMed
22. McNally, JD, Sampson, M, Matheson, LA, Hutton, B, Little, J. Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatr Pulmonol 2014; 49: 790–799.Google Scholar
23. Schaffrath Rosario, A, Schienkiewitz, A, Neuhauser, H. German height references for children aged 0 to under 18 years compared to WHO and CDC growth charts. Ann Human Biol 2011; 38: 121–130.Google Scholar
24. Schaffrath Rosario, A, Kurth, BM, Stolzenberg, H, Ellert, U, Neuhauser, H. Body mass index percentiles for children and adolescents in Germany based on a nationally representative sample (KiGGS 2003-2006). Eur J Clin Nutr 2010; 64: 341–349.CrossRefGoogle Scholar
25. Bergmann, KE, Mensink, GB. Anthropometric data and obesity. Gesundheitswesen 1999; 61: S115–S120.Google ScholarPubMed
26. John, SA, Johnson, JA, Khan, M, Driscoll, DJ, Warnes, CA, Cetta, F. Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. J Am Coll Cardiol 2014; 64: 54–62.Google Scholar
27. Uthamalingam, S, Patvardhan, EA, Subramanian, S, et al. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol 2011; 107: 433–438.Google Scholar
28. Gruppen, MP, Davin, JC, Oosterveld, MJ, et al. Prevention of steroid-induced low bone mineral density in children with renal diseases: a systematic review. Nephrol Dial Transplant 2013; 28: 2099–2106.Google Scholar
29. Liu, LC, Voors, AA, van Veldhuisen, DJ, et al. Vitamin D status and outcomes in heart failure patients. Eur J Heart Fail 2011; 13: 619–625.Google Scholar
30. Anderson, JL, Vanwoerkom, RC, Horne, BD, et al. Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent factors? Am Heart J 2011; 162: 331–339.Google Scholar
31. Gandhi, S, Myers, RB. Can parathyroid hormone be used as a biomarker for heart failure? Heart Fail Rev 2013; 18: 465–473.CrossRefGoogle ScholarPubMed
32. Inai, K, Nakanishi, T, Nakazawa, M. Clinical correlation and prognostic predictive value of neurohumoral factors in patients late after the Fontan operation. Am Heart J 2005; 150: 588–594.CrossRefGoogle ScholarPubMed
33. Saiki, H, Kuwata, S, Kurishima, C, et al. Aldosterone-cortisol imbalance immediately after Fontan operation with implications for abnormal fluid homeostasis. Am J Cardiol 2014; 114: 1578–1583.Google Scholar
34. Tomaschitz, A, Ritz, E, Pieske, B, et al. Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease. Cardiovasc Res 2012; 94: 10–19.Google Scholar
35. Avgeri, M, Papadopoulou, A, Platokouki, H, et al. Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol 2008; 30: 592–597.Google Scholar
36. Bendaly, EA, DiMeglio, LA, Fadel, WF, Hurwitz, RA. Bone density in children with single ventricle physiology. Pediatr Cardiol 2015; 36: 779–785.Google Scholar
37. Pappa, H, Thayu, M, Sylvester, F, Leonard, M, Zemel, B, Gordon, C. Skeletal health of children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2011; 53: 11–25.Google Scholar
38. Brown, JM, Vaidya, A. Interactions between adrenal-regulatory and calcium-regulatory hormones in human health. Curr Opin Endocrinol Diabetes Obes 2014; 21: 193–201.Google Scholar
39. Sharma, R, Bolger, AP, Li, W, et al. Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease. Am J Cardiol 2003; 92: 188–193.Google Scholar
40. Ostrow, AM, Freeze, H, Rychik, J. Protein-losing enteropathy after Fontan operation: investigations into possible pathophysiologic mechanisms. Ann Thorac Surg 2006; 82: 695–700.Google Scholar
41. Bode, L, Salvestrini, C, Park, PW, et al. Heparan sulphate and syndecan-1 are essential in maintaining murine and human intestinal epithelial barrier function. J Clin Invest 2008; 118: 229–238.CrossRefGoogle ScholarPubMed
42. Chueng, YF, Tsang, HY, Kwok, JS. Immunologic profile of patients with protein-losing enteropathy complicating congenital heart disease. Pediatr Cardiol 2002; 23: 587–593.Google Scholar