Cancer Causes & Control

, Volume 17, Issue 4, pp 583–589 | Cite as

Melatonin Treatment in Obese Patients with Childhood Craniopharyngioma and Increased Daytime Sleepiness

  • Hermann L. Müller
  • Georg Handwerker
  • Ursel Gebhardt
  • Andreas Faldum
  • Angela Emser
  • Reinhard Kolb
  • Niels Sörensen
Special Section on Cancer and Rhythm Original Paper


Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale [ESS]) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in severely obese (BMI≥4SD) and non severely obese (BMI<4SD) craniopharyngioma patients (n=79), patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects (n=30). Using a general linear model procedure analyzing the influence of BMI and tumor diagnosis on diurnal salivary melatonin we found that morning salivary melatonin levels were related to BMI (F test: p-value=0.004) and tumor diagnosis (F-test: p-value=0.032). Also for nighttime salivary melatonin levels significant relations with BMI (p-value in F-test: <0.001) and tumor diagnosis (p-value in F-test: 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at nighttime or in the morning showed a negative correlation (Spearman’s rho: −0.42; p=0.001; Spearman’s rho: −0.31; p=0.020) with the patient’s ESS score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of diurnal salivary cortisol concentrations were not detectable when patient groups and controls were compared. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI and hypothalamic tumor diagnosis, we initiated an experimental melatonin substitution in 10 adult obese patients (5f/5m) with childhood craniopharyngioma. In all 10 patients with childhood craniopharyngioma the degree of daytime sleepiness significantly improved based on activity diaries, ESS, self assessment questionnaires and actimetry. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As first experiences with experimental melatonin substitution were promising, further randomized double-blinded studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted.


Cortisol Craniopharyngioma Daytime sleepiness Melatonin Sleep disorders Saliva 


  1. 1.
    Einhaus SL, Sanford RA (1999) Craniopharyngiomas. In: Albright AL, Pollack IF, Adelson PD (eds) Principles and practice of Pediatric Neurosurgery. Thieme, New York, Stuttgart, pp 545–562Google Scholar
  2. 2.
    Müller-Scholden J, Lehrnbecher T, Müller HL, etal. (2000) Radical Surgery in a neonate with craniopharyngioma - Report of a case. Pediatr Neurosurg 33:265–269PubMedGoogle Scholar
  3. 3.
    Müller HL, Bueb K, Bartels U, etal. (2001) Obesity after childhood craniopharyngioma – German multicenter study on pre-operative risk factors and quality of life. Klin Pädiatr 213:244–249PubMedGoogle Scholar
  4. 4.
    Müller HL, Handwerker G, Wollny B, Sörensen N (2002) Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients. J Clin Endocrinol Metab 87:3993–3996PubMedGoogle Scholar
  5. 5.
    Müller HL, Schneider P, Etavard-Gorris N, Gebhardt U, Kolb R, Sörensen N (2003) Volumetric bone mineral density (BMD) in patients with childhood craniopharyngioma. Exp Clin Endocrinol Diabetes 111:168–173PubMedGoogle Scholar
  6. 6.
    Müller HL, Kaatsch P, Warmuth-Metz M, Flentje M, Sörensen N (2003) Kraniopharyngeom im Kindes- und Jugendalter – Diagnostische und therapeutische Strategien. Monatsschr Kinderheilkd 151:1056–1063CrossRefGoogle Scholar
  7. 7.
    Müller HL, Heinrich M, Bueb K, etal. (2003) Perioperative dexamethasone treatment in childhood craniopharyngioma – Influence on short-term and long-term weight development. J Exp Clin Endocrinol Diabetes 111:330–334Google Scholar
  8. 8.
    Bloch KE, Schoch OD, Zhang JN, Russi EW (1999) German version of the Epworth Sleepiness Scale. Respiration 66:440–447CrossRefPubMedGoogle Scholar
  9. 9.
    Brzezinski A (1997) Melatonin in humans. N Engl J Med 336:186–195CrossRefPubMedGoogle Scholar
  10. 10.
    Waldhauser F (1993) Clinical aspects of the melatonin action: impact of development, aging, and puberty. Experientia 49(8):671–681CrossRefPubMedGoogle Scholar
  11. 11.
    Rolland-Cachera MF, Cole TJ, Sempé M, Tichet J, Rossignol C, Charraud A (1991) Body mass index variations: centiles from birth to 87 years. Eur J Clin Nutrition 45:13–21 Google Scholar
  12. 12.
    Vaughan GM (1993) New sensitive serum melatonin radioimmunoassay employing the Kennaway G280 antibody: Syrian hamster morning adrenergic response. J Pineal Res 15:88–103PubMedGoogle Scholar
  13. 13.
    Laakso ML, Porkka-Heiskanen T, Alila A, Stenberg D, Johansson G (1990) Correlation between salivary and serum melatonin: dependence on serum melatonin levels. J Pineal Res 9(1):39–50PubMedGoogle Scholar
  14. 14.
    Murata J, Sawamura Y, Ikeda J, Hashimoto S, Honma K, (1998) Twenty-four hour rhythm of melatonin in patients with a history of pineal and/or hypothalamo-neurohypophyseal germinoma. J Pineal Res 25:159–166PubMedGoogle Scholar
  15. 15.
    Ostrowska Z, Buntner B, Banas I, Kos-Kudla B, Marek B, Zwirska-Korczala K (1996) Circadian variations of salivary melatonin levels in women of reproductive and postmenopausal age with gynoid and android obesity. Endocr Regul 30:143–152PubMedGoogle Scholar
  16. 16.
    Tamarkin L, Abastillas P, Chen HC, McNemar A, Sidbury JB (1982) The daily profile of plasma melatonin in obese and Prader-Willi syndrome children. J Clin Endocrinol Metab 55 (3):491–495PubMedGoogle Scholar
  17. 17.
    Birketvedt GS, Florholmen J, Sundsfjord J, etal. (1999) Behavioral and neuroendocrine characteristics of the night-eating syndrome. JAMA 282:689–690CrossRefGoogle Scholar
  18. 18.
    Harz KJ, Müller HL, Waldeck E, Pudel V, Roth C (2003) Obesity in patients with craniopharyngioma: Assessment of physical activity and food intake. J Clin Endocrinol Metab 88:5227–5231CrossRefPubMedGoogle Scholar
  19. 19.
    Müller HL, Faldum A, Etavard-Gorris N, etal. (2003) Functional capacity, obesity and hypothalamic involvement – cross-sectional study on 212 patients with childhood craniopharyngioma. Klin Pädiatr 215:310–314PubMedGoogle Scholar
  20. 20.
    Müller HL, Emser A, Faldum A, etal. (2004) Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 89:3298–3305PubMedGoogle Scholar
  21. 21.
    Müller HL, Etavard-Gorris N, Korenke E, etal. (2004) Prognosis and sequela in patients with childhood craniopharyngioma – Results of HIT-ENDO and update on KRANIOPHARYNGEOM 2000. Klin Pädiatr 216:343–348PubMedGoogle Scholar
  22. 22.
    Müller HL (2003) Childhood craniopharyngioma – Current strategies in laboratory diagnostics and endocrine treatment. Lab Med 27:377–385Google Scholar
  23. 23.
    Müller HL (2001) Kraniopharyngeom 2000 – Multizentrische, prospektive Beobachtungsstudie von Kindern und Jugendlichen mit Kraniopharyngeom. 1st edn. Verlag Isensee, Oldenburg, GermanyGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Hermann L. Müller
    • 1
  • Georg Handwerker
    • 2
  • Ursel Gebhardt
    • 1
  • Andreas Faldum
    • 3
  • Angela Emser
    • 3
  • Reinhard Kolb
    • 1
  • Niels Sörensen
    • 4
  1. 1.Department of Pediatrics, Children’s HospitalZentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg gGmbHOldenburgGermany
  2. 2.Department of PediatricsUniversity Hospital WürzburgWürzburgGermany
  3. 3.Institute for Medical Biometry, Epidemiology and InformaticsUniversity of MainzMainzGermany
  4. 4.Department of Pediatric NeurosurgeryUniversity HospitalWürzburgGermany

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