Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients

C. Invitti, L. Danesi, A. Dubini, F. Cavagnini

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 μg/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 months of sodium valproate (P <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 CRH (1 μg/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P <0.05, <0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH 200 μg 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.

Original languageEnglish
Pages (from-to)381-388
Number of pages8
JournalActa Endocrinologica
Volume118
Issue number3
Publication statusPublished - 1988

Fingerprint

Valproic Acid
Body Weight
Adrenocorticotropic Hormone
Levodopa
gamma-Aminobutyric Acid
Metyrapone
Metoclopramide
Growth
Prolactin
Anticonvulsants
Hydrocortisone
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Endocrinology

Cite this

Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients. / Invitti, C.; Danesi, L.; Dubini, A.; Cavagnini, F.

In: Acta Endocrinologica, Vol. 118, No. 3, 1988, p. 381-388.

Research output: Contribution to journalArticle

@article{0cca3a1d633941929991505c7650da19,
title = "Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients",
abstract = "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 μg/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 months of sodium valproate (P <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 CRH (1 μg/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P <0.05, <0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH 200 μg 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.",
author = "C. Invitti and L. Danesi and A. Dubini and F. Cavagnini",
year = "1988",
language = "English",
volume = "118",
pages = "381--388",
journal = "Acta Endocrinologica",
issn = "0001-5598",
publisher = "Munksgaard International Publishers",
number = "3",

}

TY - JOUR

T1 - Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients

AU - Invitti, C.

AU - Danesi, L.

AU - Dubini, A.

AU - Cavagnini, F.

PY - 1988

Y1 - 1988

N2 - 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 μg/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 months of sodium valproate (P <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 CRH (1 μg/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P <0.05, <0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH 200 μg 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.

AB - 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 μg/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 months of sodium valproate (P <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 CRH (1 μg/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P <0.05, <0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH 200 μg 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.

UR - http://www.scopus.com/inward/record.url?scp=0023785202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023785202&partnerID=8YFLogxK

M3 - Article

VL - 118

SP - 381

EP - 388

JO - Acta Endocrinologica

JF - Acta Endocrinologica

SN - 0001-5598

IS - 3

ER -