Disorder in the Serotonergic System due to Tryptophan Hydroxylation Impairment: A Cause of Hypothalamic Syndrome?

D.A. Schott, J. Nicolai, J.E. de Vries, I.M. Keularts, M.E. Rubio-Gozalbo, W.J.M. Gerver

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: The hypothalamus regulates basic homeostasis such as appetite, circadian rhythm, autonomic and pituitary functions. Dysregulation in these functions results in the hypothalamic syndrome, a rare disorder of various origins. Since serotonin (5-HT) modulates most of the above-mentioned homeostasis, a defect in the serotonergic system can possibly participate in this syndrome. Methods: We describe a girl suffering from hypothalamic syndrome with a decreased concentration of 5-hydroxytryptophan (5-HTP) and a normal level of tryptophan in the cerebrospinal fluid (CSF) suggesting a functional defect in tryptophan hydroxylase (TPH). TPH is a rate-limiting enzyme in the synthesis of the neurotransmitter 5-HT. Results: Therapeutic intervention with 5-HTP, carbidopa and a specific serotonin reuptake inhibitor significantly improved her clinical symptoms and caused biochemical normalisation of neurotransmitters. Conclusion: The girl described had the typical symptoms of a hypothalamic disorder and a defective serotonergic metabolism, a relationship which has not been reported before. Therapeutic interventions to restore 5-HT metabolism resulted in clinical improvement. We suggest that investigation of 5-HT metabolism in CSF of patients with this rare disorder is included in the aetiological work-up.
Original languageEnglish
Pages (from-to)68-73
Number of pages6
JournalHormone Research in Paediatrics
Volume73
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Serotonin
  • Tryptophan hydroxylase
  • Hypothalamus
  • TPH2 protein
  • Obesity
  • GONADOTROPIN-RELEASING-HORMONE
  • ONSET CENTRAL HYPOVENTILATION
  • ALVEOLAR HYPOVENTILATION
  • PRECOCIOUS PUBERTY
  • PINEAL-GLAND
  • DYSFUNCTION
  • RAT
  • ASSOCIATION
  • MELATONIN
  • CHILD

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