Am. J. Respir. Crit. Care Med., Vol 152, No. 1, Jul 1995, 186-192.
Abnormal serotonergic stimulation of cortisol production in obstructive sleep apnea
DW Hudgel, EA Gordon and HY Meltzer
Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Because serotonin (5-HT) precursor or reuptake inhibitors improve
obstructive sleep apnea (OSA), we hypothesized that brain serotonergic
activity may be decreased in OSA. To test this hypothesis, we measured the
cortisol response to the ingestion of L-5-hydroxytryptophan (L-5- HTP), a
5-HT precursor that is decarboxylated to 5-HT in the brain. Either L-5-HTP
or an identical-looking placebo was administered at 0800, and blood was
obtained over the following 4 h for serum cortisol determination. A
placebo-controlled ACTH stimulation test was performed to evaluate adrenal
function. We found that a group of 11 OSA patients had significantly higher
cortisol production after L-5-HTP administration compared with a group of
11 control nonapneic subjects. The pretest cortisol levels and ACTH
stimulation test results were not different between the two groups. We
conclude that the cortisol response to L-5-HTP was elevated in the OSA
patients studied, most likely as a result of increased hypophyseal 5-HT
activity. We speculate that the 5-HT postsynaptic receptors that induce
corticotropin releasing factor production and release are upregulated, or
supersensitized, as a result of a brain 5-HT-deficient state that exists
during sleep in OSA. We anticipate that medullary serotonergic neurons that
affect ventilation would be altered similarly.
