Horm Metab Res 2020; 52(07): 500-508
DOI: 10.1055/a-1169-0307
Endocrine Care

Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma

Hae Woon Jung
1   Department of Pediatrics, Kyung Hee University Medical Center, Seoul, Korea
,
Hwa Young Kim
2   Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea
,
Ji Young Kim
3   Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
,
Jung-Eun Cheon
4   Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
,
In-One Kim
4   Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
,
Seung-Ki Kim
5   Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea
,
Choong Ho Shin
3   Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
,
Sei Won Yang
3   Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
,
Young Ah Lee
3   Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
› Author Affiliations

Abstract

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10–30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.



Publication History

Received: 03 July 2019

Accepted: 27 April 2020

Article published online:
08 June 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Bülow B, Attewell R, Hagmar L. et al. Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence. J Clin Endocrinol Metab 1998; 83: 3897-3904
  • 2 Tomlinson J, Holden N, Hills R. et al. Association between premature mortality and hypopituitarism. Lancet 2001; 357: 425-431
  • 3 Pereira AM, Schmid EM, Schutte PJ. et al. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma. Clin Endocrinol (Oxf) 2005; 62: 197-204
  • 4 Olsson DS, Andersson E, Bryngelsson I-L. et al. Excess mortality and morbidity in patients with craniopharyngioma, especially in patients with childhood onset: A population-based study in Sweden. J Clin Endocrinol Metab 2015; 100: 467-474
  • 5 Wijnen M, Olsson DS, van den Heuvel-Eibrink MM. et al. Excess morbidity and mortality in patients with craniopharyngioma: A hospital-based retrospective cohort study. Eur J Endocrinol 2018; 178: 93-102
  • 6 Standl E. Aetiology and consequences of the metabolic syndrome. Eur Heart J Suppl 2005; 7: D10-D13
  • 7 Holmer H, Ekman B, Björk J. et al. Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy. Eur J Endocrinol 2009; 161: 671-679
  • 8 Simoneau-Roy J, O’Gorman C, Pencharz P. et al. Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma. Clin endocrinol (Oxf) 2010; 72: 364-370
  • 9 Sahakitrungruang T, Klomchan T, Supornsilchai V. et al. Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery. Eur J Pediatr 2011; 170: 763-769
  • 10 Wijnen M, Olsson DS, van den Heuvel-Eibrink MM. et al. The metabolic syndrome and its components in 178 patients treated for craniopharyngioma after 16 years of follow-up. Eur J Endocrinol 2018; 178: 11-22
  • 11 Wulsin LR, Horn PS, Perry JL. et al. Autonomic imbalance as a predictor of metabolic risks, cardiovascular disease, diabetes, and mortality. J Clin Endocrinol Metab 2015; 100: 2443-2448
  • 12 Licht CM, de Geus EJ, Penninx BW. Dysregulation of the autonomic nervous system predicts the development of the metabolic syndrome. J Clin Endocrinol Metab 2013; 98: 2484-2493
  • 13 Lustig RH. Hypothalamic obesity: The sixth cranial endocrinopathy. Endocrinologist 2002; 12: 210-217
  • 14 Hochberg I, Hochberg Z. Expanding the definition of hypothalamic obesity. Obes Rev 2010; 11: 709-721
  • 15 Roth CL, Hunneman DH, Gebhardt U. et al. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res 2007; 61: 496-501
  • 16 Rg Coutant, Hln Maurey, Sp Rouleau. et al. Defect in epinephrine production in children with craniopharyngioma: Functional or organic origin?. J Clin Endocrinol Metab 2003; 88: 5969-5975
  • 17 Cohen M, Syme C, McCrindle BW. et al. Autonomic nervous system balance in children and adolescents with craniopharyngioma and hypothalamic obesity. Eur J Endocrinol 2013; 168: 845-852
  • 18 Puget S, Garnett M, Wray A. et al. Pediatric craniopharyngiomas: Classification and treatment according to the degree of hypothalamic involvement. J Neurosurg 2007; 106: 3-12
  • 19 Moon JS, Lee SY, Nam CM. et al. 2007 Korean National Growth Charts: Review of developmental process and an outlook. Korean J Pediatr 2008; 51: 1-25
  • 20 World Health Organization International Obesity Taskforce The Asia-Pacific perspective: Redefining obesity and its treatment. Sydney: Health Communications. Australia: 2000
  • 21 Zimmet P, Alberti G, Kaufman F. et al. The metabolic syndrome in children and adolescents. Lancet 2007; 369: 2059-2061
  • 22 Craig CL, Marshall AL, Sjöström M. et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003; 35: 1381-1395
  • 23 2018 Physcial Activity Guidelines Advisory Committee 2018 Physical activity guidelines advisory committee scientific report. Washington, DC: US Department of Health and Human Services; 2018
  • 24 Task Force of the European Society of Cardiology and The North Americal Society of Pacing and Electrophysiology Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Eur Heart J 1996; 17: 354-381
  • 25 Malliani A, Pagani M, Lombardi F. et al. Cardiovascular neural regulation explored in the frequency domain. Circulation 1991; 84: 482-492
  • 26 Montano N, Ruscone TG, Porta A. et al. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation 1994; 90: 1826-1831
  • 27 Berntson GG, Bigger JT, Eckberg DL. et al. Heart rate variability: Origins, methods and interpretive caveats. Psychophysiology 1997; 34: 623-648
  • 28 Houle MS, Billman GE. Low-frequency component of the heart rate variability spectrum: A poor marker of sympathetic activity. Am J Physiol 1999; 276: H215-H223
  • 29 Goldstein DS, Bentho O, Park MY. et al. Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation nof cardiac autonomic outflows by baroreflexes. Exp Physiol 2011; 96: 1255-1261
  • 30 Srinivasan S, Ogle G, Garnett S. et al. Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 2004; 89: 81-86
  • 31 Min KB, Min JY, Paek D. et al. The impact of the components of metabolic syndrome on heart rate variability: Using the NCEP-ATP III and IDF definitions. Pacing Clin Electrophysiol 2008; 31: 584-591
  • 32 Chang CJ, Yang YC, Lu FH. et al. Altered cardiac autonomic function may precede insulin resistance in metabolic syndrome. Am J Med 2010; 123: 432-438
  • 33 Zhou Y, Xie G, Wang J. et al. Cardiovascular risk factors significantly correlate with autonomic nervous system activity in children. Can J Cardiol 2012; 28: 477-482
  • 34 Altuncu ME, Baspinar O, Keskin M. The use of short-term analysis of heart rate variability to assess autonomic function in obese children and its relationship with metabolic syndrome. Cardiol J 2012; 19: 501-506
  • 35 Umetani K, Singer DH, McCraty R. et al. Twenty-four hour time domain heart rate variability and heart rate: Relations to age and gender over nine decades. J Am Coll Cardiol 1998; 31: 593-601
  • 36 Sajadieh A, Nielsen OW, Rasmussen V. et al. Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 2004; 25: 363-370
  • 37 Kim HG, Cheon EJ, Bai DS. et al. Stress and heart rate variability: A meta-analysis and review of the literature. Psychiatry Investig 2018; 15: 235-245
  • 38 Karason K, Mølgaard H, Wikstrand J. et al. Heart rate variability in obesity and the effect of weight loss. Am J Cardiol 1999; 83: 1242-1247
  • 39 Birch SL, Duncan MJ, Franklin C. Overweight and reduced heart rate variability in British children: An exploratory study. Prev Med 2012; 55: 430-432
  • 40 Pop-Busui R. Cardiac autonomic neuropathy in diabetes: A clinical perspective. Diabetes Care 2010; 33: 434-441
  • 41 Habek JC, Lakusic N, Kruzliak P. et al. Left ventricular diastolic function in diabetes mellitus type 2 patients: Correlation with heart rate and its variability. Acta Diabetol 2014; 51: 999-1005
  • 42 Kubota Y, Chen LY, Whitsel EA. et al. Heart rate variability and lifetime risk of cardiovascular disease: The atherosclerosis risk in communities study. Ann Epidemiol 2017; 27: 619-625
  • 43 Maheshwari A, Norby FL, Soliman EZ. et al. Low heart rate variability in a 2-minute electrocardiogram recording is associated with an increased risk of sudden cardiac death in the general population: The atherosclerosis risk in communities study. PLoS One 2016; 11: e0161648
  • 44 Shah SA, Kambur T, Chan C. et al. Relation of short-term heart rate variability to incident heart failure (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 2013; 112: 533-540
  • 45 Dekker JM, Schouten EG, Klootwijk P. et al. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men: The zutphen study. Am J Epidemiol 1997; 145: 899-908
  • 46 May O, Arildsen H. Long-term predictive power of heart rate variability on all-cause mortality in the diabetic population. Acta Diabetol 2011; 48: 55-59
  • 47 Licht CM, Vreeburg SA, van Reedt Dortland AK. et al. Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic-pituitary-adrenal axis activity is associated with metabolic abnormalities. J Clin Endocrinol Metab 2010; 95: 2458-2466
  • 48 Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol 2010; 141: 122-131
  • 49 Billman GE. The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance. Front Physiol 2013; 4: 26
  • 50 Seoane-Collazo P, Fernø J, Gonzalez F. et al. Hypothalamic-autonomic control of energy homeostasis. Endocrine 2015; 50: 276-291