Disorder in the serotonergic system due to tryptophan hydroxylation impairment: a cause of hypothalamic syndrome?
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.


CONCLUSIONS
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.
Schott
D A
DA
Department of Paediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands. da.schott@mumc.nl
Nicolai
J
J
de Vries
J E
JE
Keularts
I M L W
IM
Rubio-Gozalbo
M E
ME
Gerver
W J M
WJ
D002675:Child, Preschool; D004700:Endocrine System Diseases / Q000134:cerebrospinal fluid / Q000150:complications* / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation / Q000235:genetics / Q000502:physiology; D007027:Hypothalamic Diseases / Q000209:etiology* / Q000378:metabolism; D008954:Models, Biological; D009765:Obesity / Q000175:diagnosis / Q000209:etiology; D012701:Serotonin / Q000378:metabolism*; D013577:Syndrome; D014364:Tryptophan / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D012701:Serotonin; D014364:Tryptophan; D014365:Tryptophan Hydroxylase