Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients.
In 10 untreated epileptic patients, we evaluated the functional integrity of the hypothalamic-pituitary axis before and during chronic treatment with sodium valproate, a gamma-aminobutyric acid-mimetic compound. The GH response to L-dopa (250-500 mg po) was absent in 3 and severely impaired in 2 of the 10 patients though being, on the average, only slightly lower in the epileptic subjects than in normal controls. Conversely, the GH rise following GHRH (0.5 micrograms/kg body weight, iv) was normal in 9 of the patients. A significant blunting of the GH response to L-dopa occurred in the 7 patients initially responsive after 6 month of sodium valproate (P less than 0.05). The GH response to GHRH also underwent an evident though not significant attenuation. The ACTH and the ACTH/cortisol elevations elicited by metyrapone (35 mg/kg body weight infused over 4 h), and by CRH (1 microgram/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P less than 0.05, less than 0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH (200 micrograms iv) remained normal over the whole study period. Growth arrest ensued in 1 patient after 6 months of sodium valproate and disappeared after drug withdrawal. These observations point to a defective hypothalamic control of GH secretion in some epileptic patients. They also indicate that chronic administration of sodium valproate, hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion. Occasionally, a reversible arrest of skeletal growth may also ensue.
Invitti
C
C
Institute of Medical Sciences, University of Milan, Italy.
Danesi
L
L
Dubini
A
A
Cavagnini
F
F
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D002648:Child; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D014635:Valproic Acid / Q000008:administration & dosage*
D007980:Levodopa; D014635:Valproic Acid; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone