CoChat
Sign Up
Cited by 5Pituitary Gland Disorders and TreatmentsHeart Rate Variability and Autonomic ControlHypothalamic control of reproductive hormones

Cardiac autonomic dysfunction is associated with hypothalamic damage in patients with childhood-onset craniopharyngioma

Open access
Jung, Hae Woon, Kim, Hwa Young, Kim, Ji Young, Cheon, Jung-Eun, Kim, In-One, Kim, Seung-Ki, Shin, Choong Ho, Yang, Sei Won +1 more·2021·PLOS ONE
DOI 10.1371/journal.pone.0246789PMC PMC7886170
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Autonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma. Methods: A cross-sectional study of 48 patients (28 males, 10–30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured. Results: Patients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity. Conclusions: The reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0246789

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Decreased heart rate variability is a manifestation of autonomic impairment that has been demonstrated in individuals with hypothalamic injury.

    “Decreased heart rate variability, the loss of the typical beat-to-beat fluctuation in rhythm, is a manifestation of autonomic impairment that has been demonstrated in individuals with hypothalamic injury (57, 58).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [58]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. [1]Müller HL. Paediatrics: surgical strategy and quality of life in craniopharyngioma. Nat Rev Endocrinol. 2013; 9: 447– 449. 10.1038/nrendo.2013.125 23797818 · DOI
  2. [2]Sterkenburg AS, Hoffmann A, Gebhardt U, Warmuth-Metz M, Daubenbuchel AM, Müller HL. Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro Oncol. 2015; 17: 1029– 1038. 10.1093/neuonc/nov044 25838139 PMC5654354 · DOI
  3. [3]Roth C, Wilken B, Hanefeld F, Schöter W, Leonhardt U. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol. 1998; 138: 89– 91. 10.1530/eje.0.1380089 9461323 · DOI
  4. [4]Roth CL. Hypothalamic obesity in patients with craniopharyngioma: profound changes of several weight regulatory circuits. Front Endocrinol (Lausanne). 2011; 2: 49 10.3389/fendo.2011.00049 22654811 PMC3356147 · DOI
  5. [5]Roth CL. Hypothalamic obesity in craniopharyngioma patients: disturbed energy homeostasis related to extent of hypothalamic damage and its implication for obesity intervention. J Clin Med. 2015; 4: 1774– 1797. 10.3390/jcm4091774 26371051 PMC4600159 · DOI
  6. [6]Seoane-Collazo P, Fernø J, Gonzalez F, Diéguez C, Leis R, Nogueiras R, et al Hypothalamic-autonomic control of energy homeostasis. Endocrine. 2015; 50: 276– 291. 10.1007/s12020-015-0658-y 26089260 · DOI
  7. [7]Roth CL, Hunneman DH, Gebhardt U, Stoffel-Wagner B, Reinehr T, Müller HL. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res. 2007; 61: 496– 501. 10.1203/pdr.0b013e3180332cd6 17515878 · DOI
  8. [8]Coutant R, Maurey H, Rouleau S, Mathieu E, Mercier P, Limal JM, et al A Defect in epinephrine production in children with craniopharyngioma: functional or organic origin? J Clin Endocrinol Metab. 2003; 88: 5969– 5975. 10.1210/jc.2003-030552 14671198 · DOI
  9. [9]Simoneau-Roy J, O’Gorman C, Pencharz P, Adeli K, Daneman D, Hamilton J. Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma. Clin Endocrinol (Oxf). 2010; 72: 364– 370. 10.1111/j.1365-2265.2009.03639.x 19486023 · DOI
  10. [10]Chen GY, Hsiao TJ, Lo HM, Kuo CD. Abdominal obesity is associated with autonomic nervous derangement in healthy Asian obese subjects. Clin Nutr. 2008; 27: 212– 217. 10.1016/j.clnu.2007.11.004 18234399 · DOI
  11. [11]Windham BG, Fumagalli S, Ble A, Sollers JJ, Thayer JF, Najjar SS, et al The relationship between heart rate variability and adiposity differs for central and overall adiposity. J Obes. 2012; 2012: 149516 10.1155/2012/149516 22649714 PMC3357556 · DOI
  12. [12]Puget S, Garnett M, Wray A, Grill J, Habrand JL, Bodaert N, et al Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg. 2007; 106(1 Suppl): 3– 12. 10.3171/ped.2007.106.1.3 17233305 · DOI
  13. [13]Moon JS, Lee SY, Nam CM, Choi J-M, Choe B-K, Seo J-W, et al 2007 Korean National Growth Charts: review of developmental process and an outlook. Korean Journal of Pediatrics. 2008; 51: 1– 25.
  14. [15]Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003; 35: 1381– 1395. 10.1249/01.MSS.0000078924.61453.FB 12900694 · DOI · Paper page
  15. [17]Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J. 1996; 17: 354– 81. 8737210
  16. [18]Meuric S, Brauner R, Trivin C, Souberbielle JC, Zerah M, Sainte-Rose C. Influence of tumor location on the presentation and evolution of craniopharyngiomas. J Neurosurg. 2005; 103(5 Suppl): 421– 426. 10.3171/ped.2005.103.5.0421 16302613 · DOI
  17. [19]de Vile CJ, Grant DB, Hayward RD, Kendall BE, Neville BG, Stanhope R. Obesity in childhood craniopharyngioma: relation to post-operative hypothalamic damage shown by magnetic resonance imaging. J Clin Endocrinol Metab. 1996; 81: 2734– 2737. 10.1210/jcem.81.7.8675604 8675604 · DOI
  18. [20]Park SW, Jung HW, Lee YA, Shin CH, Yang SW, Cheon JE, et al Tumor origin and growth pattern at diagnosis and surgical hypothalamic damage predict obesity in pediatric craniopharyngioma. J Neurooncol. 2013; 113: 417– 424. 10.1007/s11060-013-1128-0 23579339 PMC3684719 · DOI
  19. [21]Roth CL, Eslamy H, Werny D, Elfers C, Shaffer ML, Pihoker C, et al Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity. Obesity (Silver Spring). 2015; 23: 1226– 1233. 10.1002/oby.21067 25884561 PMC5029599 · DOI · Paper page
  20. [22]Bereket A, Kiess W, Lustig RH, Muller HL, Goldstone AP, Weiss R, et al Hypothalamic obesity in children. Obes Rev. 2012; 13(9): 780– 798. 10.1111/j.1467-789X.2012.01004.x 22577758 · DOI
  21. [23]Elowe-Gruau E, Beltrand J, Brauner R, Pinto G, Samara-Boustani D, Thalassinos C, et al Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J Clin Endocrinol Metab. 2013; 98: 2376– 2382. 10.1210/jc.2012-3928 23633208 · DOI
  22. [24]Lustig RH. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment. Front Endocrinol (Lausanne). 2011; 2: 60 10.3389/fendo.2011.00060 22654817 PMC3356006 · DOI
  23. [25]Valensi P, Doaré L, Perret G, Germack R, Pariès J, Mesangeau D. Cardiovascular vagosympathetic activity in rats with ventromedial hypothalamic obesity. Obes Res. 2003; 11: 54– 64. 10.1038/oby.2003.10 12529486 · DOI
  24. [26]Lustig RH, Rose SR, Burghen GA, Velasquez-Mieyer P, Broome DC, Smith K, et al Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr. 1999; 135(2): 162– 168. 10.1016/s0022-3476(99)70017-x 10431109 · DOI
  25. [27]Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, et al Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2003; 88: 2586– 2592. 10.1210/jc.2002-030003 12788859 · DOI
  26. [28]Guran T, Turan S, Bereket A, Akcay T, Unluguzel G, Bas F, et al The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children. Eur J Pediatr. 2009; 168: 1043– 1048. 10.1007/s00431-008-0876-x 19043735 · DOI
  27. [29]Cohen M, Syme C, McCrindle BW, Hamilton J. Autonomic nervous system balance in children and adolescents with craniopharyngioma and hypothalamic obesity. Eur J Endocrinol. 2013; 168: 845– 852. 10.1530/EJE-12-1082 23482594 · DOI
  28. [30]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. 10.5603/cj.2012.0091 23042314 · DOI
  29. [31]Baum P, Petroff D, Classen J, Kiess W, Blüher S. Dysfunction of autonomic nervous system in childhood obesity: a cross-sectional study. PLoS One. 2013; 8: e54546 10.1371/journal.pone.0054546 23358101 PMC3554723 · DOI
  30. [32]Rabbia F, Silke B, Conterno A, Grosso T, De Vito B, Rabbone I, et al Assessment of cardiac autonomic modulation during adolescent obesity. Obes Res. 2003; 11: 541– 548. 10.1038/oby.2003.76 12690083 · DOI
  31. [33]Martini G, Riva P, Rabbia F, Molini V, Ferrero GB, Cerutti F, et al Heart rate variability in childhood obesity. Clin Auton Res. 2001; 11: 87– 91. 10.1007/BF02322051 11570608 · DOI
  32. [34]Riva P, Martini G, Rabbia F, Milan A, Paglieri C, Chiandussi L, et al Obesity and autonomic function in adolescence. Clin Exp Hypertens. 2001; 23: 57– 67. 10.1081/ceh-100001197 11270589 · DOI
  33. [36]Tsuji H, Larson MG, Venditti FJ Jr., Manders ES, Evans JC, Feldman CL, et al Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996; 94: 2850– 2855 10.1161/01.cir.94.11.2850 8941112 · DOI · Paper page
  34. [37]Kleiger RE, Miller JP, Bigger JT Jr., Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987; 59: 256– 262. 10.1016/0002-9149(87)90795-8 3812275 · DOI · Paper page
  35. [38]Bigger JT Jr., Fleiss JL, Rolnitzky LM, Steinman RC. Frequency domain measures of heart period variability to assess risk late after myocardial infarction. J Am Coll Cardiol. 1993; 21: 729– 736. 10.1016/0735-1097(93)90106-b 8436755 · DOI
  36. [39]Habek JC, Lakusic N, Kruzliak P, Sikic J, Mahovic D, Vrbanic L. Left ventricular diastolic function in diabetes mellitus type 2 patients: correlation with heart rate and its variability. Acta Diabetol. 2014; 51: 999– 1005. 10.1007/s00592-014-0658-z 25274395 · DOI
  37. [41]Wulsin LR, Horn PS, Perry JL, Massaro JM, D’Agostino RB. Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality. J Clin Endocrinol Metab. 2015; 100: 2443– 2448. 10.1210/jc.2015-1748 26047073 · DOI
  38. [42]Zhou Y, Xie G, Wang J, Yang S. Cardiovascular risk factors significantly correlate with autonomic nervous system activity in children. Can J Cardiol. 2012; 28: 477– 482. 10.1016/j.cjca.2012.02.003 22560462 · DOI
  39. [43]Jung HW, Kim HY, Kim JY, Cheon JE, Kim IO, Kim SK, et al Autonomic dysfunction is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma. Horm Metab Res. 2020; 52: 500– 508. 10.1055/a-1169-0307 32512610 · DOI · Paper page

Cited by

Sorted by citations

Authors
Jung, H. W., Kim, H. Y., Kim, J. Y., Cheon, J.-E., Kim, I.-O., Kim, S.-K., Shin, C. H., Yang, S. W., & Lee, Y. A.
Affiliations
  • Kyung Hee University Medical Center (KR)
  • Seoul National University (KR)
Corresponding author
Lee, Young Ah
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2021-02-16
Volume
16
Issue
2
Pages
e0246789
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0246789
PMC
PMC7886170
OpenAlex
W3132957625
Cited by
5
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2022: 1
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Seoul National University Hospital Research Fund (04-2013-0430)
  • Seoul National University College of Medicine Research Foundation (800-20130469)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
cardiac autonomic dysfunction, hypothalamic injury, childhood-onset craniopharyngioma, heart rate variability, abdominal obesity, hypothalamic obesity, parasympathetic modulation, sympathetic modulation, autonomic nervous system
MeSH terms
Adolescent, Adult, Autonomic Nervous System, Child, Craniopharyngioma, Female, Heart Diseases, Heart Rate, Humans, Magnetic Resonance Imaging, Male, Pituitary Neoplasms, Body Mass Index, Pediatric Obesity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review