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. 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.

Immunoreactive somatomedin B (RIA-B) in the circulation of healthy adults and patients with endocrine disorders.

The serum and cerebrospinal fluid (CSF) levels of immunoreactive somatomedin B (RIA-B) were examined throughout life in healthy adult humans. A significant decline in serum RIA-B was observed in subjects over 60 years of age. No significant diurnal, daily, or monthly serum variation was observed in healthy subjects aged 20-60 years. However, women taking oral contraceptives had elevated RIA-B values. No significant decline in CSF RIA-B was observed in subjects over 60 years of age. A significantly lower level of RIA-B in CSF was observed in subjects sampled at 20.00 h compared to subjects sampled in the morning. A significant decline in serum RIA-B was observed in patients with hypopituitarism and diabetes mellitus and a significant elevation of serum RIA-B levels was observed in patients with hyperthyroidism. CSF RIA-B was significantly elevated in patients with Cushing's syndrome.

PIP: The polypeptide called somatomedin B was radioimmunoassayed in serum or cerebrospinal fluid from volunteers throughout the lifespan, the daily and menstrual cycles, in oral contraceptive users, and in several patients with endocrinological disorders. This peptide, of 5000 molecular weight, is said to have insulin-like growth promoting activity, but its actual origin and function are unknown. In serum, there were no significant variations between the sexes, over the ages 20-60, in the diurnal or menstrual cycle, or by height, weight or body surface. There were significant declines after the age of 60 and 70 years in serum. The serum level in 8 women aged 20-40 taking oral contraceptives was significantly higher than that of 46 drug free women (p.001). In cerebrospinal fluid, there was a diurnal variation, a nadir at 2000 hours, but there was no decline in older individuals. Somatomedin B was significantly lower in patients with hypopituitarism and diabetes mellitus, and higher in those with hyperthyroidism and Cushing's syndrome. This is the first demonstration of somatomedin B in cerebrospinal fluid.