Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

See all formats and pricing
More options …
Volume 27, Issue 1-2


Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study

Vincenzo Salpietro / Kshitij Mankad
  • Department of Pediatrics, University of Messina, Messina, Italy
  • Great Ormond Street Children’s Hospital, London, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maria Kinali / Ashok Adams
  • Department of Pediatrics, University of Messina, Messina, Italy
  • Great Ormond Street Children’s Hospital, London, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mariella Valenzise / Gaetano Tortorella / Eloisa Gitto / Agata Polizzi
  • National Centre for Rare Diseases, Superior Institute of Health, Rome, Italy
  • Institute of Neurological Sciences, National Research Council (CNR), Catania, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Valeria Chirico / Francesco Nicita / Emanuele David / Anna Claudia Romeo / Carlo Attilio Squeri
  • Ophthalmology Unit, Department of Experimental Medical Surgical Sciences and Odontostomatology, University of Messina, Messina, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Salvatore Savasta / Gian Luigi Marseglia / Teresa Arrigo / Conrad Earl Johanson
  • Department of Pediatrics, University of Messina, Messina, Italy
  • Department of Neurosurgery, Brown University, Providence, Rhode Island, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Martino Ruggieri
  • Department of Pediatrics, University of Messina, Messina, Italy
  • Department of Educational Sciences, University of Catania, Catania, Italy
  • Unit of Neurosurgery, University of Catania, Catania, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-09-11 | DOI: https://doi.org/10.1515/jpem-2013-0156


Aim: To unravel the potential idiopathic intracranial hypertension (IIH) endocrine-metabolic comorbidities by studying the natural (and targeted drug-modified) history of disease in children. IIH is a disorder of unclear pathophysiology, characterized by raised intracranial pressure without hydrocephalus or space-occupying lesion coupled with normal cerebrospinal fluid (CSF) composition.

Methods: Retrospective study (years 2001–2010) of clinical records and images and prospective follow-up (years 2010–2013) in 15 children (11 girls, 4 boys; aged 5–16 years) diagnosed previously as “IIH”, according to the criteria for pediatric IIH proposed by Rangwala, at four university pediatric centers in northern, central, and southern Italy.

Results: We identified six potential endocrine-metabolic comorbidities including, weight gain and obesity (n=5), recombinant growth hormone therapy (n=3), obesity and metabolic syndrome (n=1), secondary hyperaldosteronism (n=1), hypervitaminosis A (n=1), and corticosteroid therapy (n=1). Response to etiologically targeted treatments (e.g., spironolactone, octreotide) was documented.

Conclusions: IIH is a protean syndrome caused by various potential (risk and) associative factors. Several conditions could influence the pressure regulation of CSF. An endocrine-metabolic altered homeostasis could be suggested in some IIH patients, and in this context, etiologically targeted therapies (spironolactone) should be considered

Keywords: aldosterone; childhood obesity; children; idiopathic intracranial hypertension; magnetic resonance imaging; metabolic syndrome; pseudotumor cerebri; spironolactone


  • 1.

    Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT, O’Fallon WM. Idiopathic intracranial hypertension (pseudotumour cerebri): descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol 1993;50:78–80.Google Scholar

  • 2.

    Hacifazlioglu Eldes N, Yilmaz Y. Pseudotumour cerebri in children: etiological, clinical features and treatment modalities. Eur J Paediatr Neurol 2012;16:349–55.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 3.

    Per H, Canpolat M, Gümüş H, Poyrazoğlu HG, Yıkılmaz A, et al. Clinical spectrum of the pseudotumor cerebri in children: etiological, clinical features, treatment and prognosis. Brain Dev 2013;35:561–8.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 4.

    Distelmaier F, Sengler U, Messing-Juenger M, Assmann B, Mayatepek E, et al. Pseudotumor cerebri as an important differential diagnosis of papilledema in children. Brain Dev 2006;28:190–5.Web of SciencePubMedCrossrefGoogle Scholar

  • 5.

    Shapiro I, Shapiro SK. Familial pseudotumor cerebri and the empty sella syndrome. Ann Ophthalmol 1980;12:1045–8.PubMedGoogle Scholar

  • 6.

    Curry WT Jr, Butler WE, Barker FG II. Rapidly rising incidence of cerebrospinal fluid shunting procedures for idiopathic intracranial hypertension in the United States, 1988–2002. Neurosurgery 2005;57:97–108.Google Scholar

  • 7.

    Wall M, George D. Idiopathic intracranial hypertension. A prospective study of 50 patients. Brain 1991;114:155–80.Google Scholar

  • 8.

    Lessell S. Pediatric pseudotumor cerebri (idiopathic intracranial hypertension). Surv Ophthalmol 1992;37:155–66CrossrefPubMedGoogle Scholar

  • 9.

    Wang SJ, Silberstein SD, Patterson S, Young WB. Idiopathic intracranial hypertension without papilledema. A case-control study in a headache center. Neurology 1998;51:245–49.CrossrefGoogle Scholar

  • 10.

    Lipton HL, Michelson PE. Pseudotumor cerebri syndrome without papilledema. J Am Med Assoc 1972;220:1591–2.Google Scholar

  • 11.

    Rush JA. Pseudotumor cerebri: clinical profile and visual outcome in 63 patients. Mayo Clin Proc 1980;55:541–6.PubMedGoogle Scholar

  • 12.

    Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, 2nd ed. Cephalalgia 2004;24(Suppl 1):9–160.Google Scholar

  • 13.

    Rangwala LM, Liu GT. Pediatric idiopathic intracranial hypertension. Surv Ophthalmol 2007;52:597–617.CrossrefPubMedGoogle Scholar

  • 14.

    Phillips PH. Pediatric pseudotumor cerebri. Int Ophthalmol Clin 2012;52:51–9.PubMedCrossrefGoogle Scholar

  • 15.

    Traviesa DC, Schwartzman RJ, Glaser JS, Savino P. Familial benign intracranial hypertension. J Neurol Neurosurg Psychiatry 1976;39:420–3.PubMedCrossrefGoogle Scholar

  • 16.

    Malm J, Kristensen B, Markgren P, Ekstedt J. CSF hydrodynamics in idiopathic intracranial hypertension: a long-term study. Neurology 1992;42:851–8.PubMedCrossrefGoogle Scholar

  • 17.

    Salpietro V, Polizzi A, Bertè LF, Chimenz R, Chirico V, et al. Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis. Neuro Endocrinol Lett 2012;33:569–73.PubMedGoogle Scholar

  • 18.

    Weig SG. Asymptomatic idiopathic intracranial hypertension in young children. J Child Neurol 2002;17:239–41.CrossrefPubMedGoogle Scholar

  • 19.

    Biousse V, Bruce BB, Newman NJ. Update on the pathophysiology and management of idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 2012;83:488–94.Web of ScienceCrossrefPubMedGoogle Scholar

  • 20.

    Salpietro V, Ruggieri M, Sancetta F, Colavita L, D’Angelo G, et al. New insights on the relationship between pseudotumor cerebri and secondary hyperaldosteronism in children. J Hypertens 2012;30:629–30.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 21.

    Weber KT. Aldosteronism revisited: perspectives on less well recognized actions of aldosterone. J Lab Clin Med 2003; 142:71–82.Google Scholar

  • 22.

    Khan MU, Khalid H, Salpietro V, Weber KT. idiopathic intracranial hypertension associated with either primary or secondary aldosteronism. Am J Med Sci 2012 [Epub ahead of print].Web of ScienceGoogle Scholar

  • 23.

    Malozowski S, Tanner LA, Wysowski D, Fleming GA. Growth hormone, insulin like growth factor 1, and benign intracranial hypertension. N Engl J Med 1993;329:665–6.Google Scholar

  • 24.

    Johansson JO, Larson G, Andersson M, Elmgren A, Hynsjo L, et al. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. Neuroendocrinology 1995;61:57–66.CrossrefPubMedGoogle Scholar

  • 25.

    Ho KY, Weissberger AJ. The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system. Metabolism 1990;39:133–7.CrossrefPubMedGoogle Scholar

  • 26.

    Panagopoulos GN, Deftereos SN, Tagaris GA, Gryllia M, Kounadi T, et al. Octreotide: a therapeutic option for idiopathic intracranial hypertension. Neurol Neurophysiol Neurosci 2007:1.PubMedGoogle Scholar

  • 27.

    Katz SE, Klisovic DD, O’Dorisio MS, Lynch R, Lubow M. Expression of somatostatin receptors 1 and 2 in human choroid plexus and arachnoid granulations: implications for idiopathic intracranial hypertension. Arch Ophthalmol 2002;120:1540–3.PubMedCrossrefGoogle Scholar

  • 28.

    Sugerman H, Windsor A, Bessos M, Wolfe L. Intra-abdominal pressure, sagittal abdominal diameter and obesity comorbidity. J Intern Med 1997;241:71–9.Google Scholar

  • 29.

    Whiteley W, Al-Shahi R, Warlow CP, Zeidler M, Lueck CJ. CSF opening pressure: reference interval and the effect of body mass index. Neurology 2006;67:1690–1.CrossrefWeb of SciencePubMedGoogle Scholar

  • 30.

    Sinclair AJ, Ball AK, Burdon MA, Clarke CE, Stewart PM, et al. Exploring the pathogenesis of IIH: an inflammatory perspective. J Neuroimmunol 2008;201–202:212–20.Web of ScienceGoogle Scholar

  • 31.

    Lampl Y, Eshel Y, Kessler A, Fux A, Gilad R, et al. Serum leptin level in women with idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 2002;72:642–3.PubMedCrossrefGoogle Scholar

  • 32.

    Whaley-Connell A, Johnson MS, Sowers JR. Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. Prog Cardiovasc Dis 2010;52:401–9.CrossrefWeb of ScienceGoogle Scholar

  • 33.

    Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 2003;100:14211–6.CrossrefGoogle Scholar

  • 34.

    Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, et al. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation 2008;117:2253–61.Web of ScienceGoogle Scholar

  • 35.

    Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, et al. Obesity and the metabolic syndrome in children and adolescent N Engl J Med 2004;350:2362–74.Google Scholar

  • 36.

    Brara SM, Koebnick C, Porter AH, Langer-Gould A. Pediatric idiopathic intracranial hypertension and extreme childhood obesity. J Pediatr 2012;161:602–7.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 37.

    Salpietro V, Chimenz R, Arrigo T, Ruggieri M. Pediatric idiopathic intracranial hypertension and extreme childhood obesity: a role of weight gain. J Pediatr 2013;162:1084.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 38.

    Zada G, Tirosh A, Kaiser UB, Laws ER, Woodmansee WW. Cushing’s disease and idiopathic intracranial hypertension: case report and review of underlying pathophysiological mechanisms J Clin Endocrinol Metab 2010;95:4850–4.CrossrefWeb of ScienceGoogle Scholar

  • 39.

    Sinclair AJ, Onyimba CU, Khosla P, Vijapurapu N, Tomlinson JW, et al. Corticosteroids, 11beta-hydroxysteroid dehydrogenase isozymes and the rabbit choroid plexus. J Neuroendocrinol 2007;19:614–20.CrossrefWeb of ScienceGoogle Scholar

  • 40.

    Sowers JR, Whaley-Connell A, Epstein M. The emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann Intern Med 2009;150:776–83.Google Scholar

  • 41.

    Kushida A, Tamura H. Retinoic acids induce neurosteroid biosynthesis in human glial GI-1 cells via the induction of steroidogenic genes. J Biochem 2009;146:917–23.Web of ScienceGoogle Scholar

About the article

Corresponding author: Vincenzo Salpietro, MD, Unit of Genetics and Pediatric Immunology, Department of Pediatrics, University of Messina, Policlinico Universitario “Gaetano Martino”, Via Consolare Valeria, 1 98125 Messina, Italy, Phone: +39 090 2213115, Fax: +39 090 2217029, E-mail:

Received: 2013-04-21

Accepted: 2013-08-06

Published Online: 2013-09-11

Published in Print: 2014-01-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 27, Issue 1-2, Pages 107–115, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2013-0156.

Export Citation

©2014 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Vincenzo Salpietro, Agata Polizzi, Gaia Recca, and Martino Ruggieri
Multiple Sclerosis and Demyelinating Disorders, 2018, Volume 3, Number 1
Grace L. Paley, Claire A. Sheldon, Evanette K. Burrows, Marianne R. Chilutti, Grant T. Liu, and Shana E. McCormack
American Journal of Ophthalmology, 2015, Volume 159, Number 2, Page 344
Vincenzo Salpietro and Martino Ruggieri
Headache: The Journal of Head and Face Pain, 2014, Volume 54, Number 7, Page 1229

Comments (0)

Please log in or register to comment.
Log in