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Journal of Clinical Endocrinology & Metabolism Vol. 56, No. 5 985-991
doi:10.1210/jcem-56-5-985
Copyright © 1983 by the Endocrine Society.
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The Evaluation of Sodium Valproate in the Treatment of Nelson's Syndrome*

Anne Dornhorst, John S. Jenkins, Steven W. J. Lamberts, Ralph R. Abraham, Victor Wynn, Ursula Beckford, Brian Gillham and Mortyn T. Jones

Alexander Simpson Laboratory for Metabolic Research, St. Mary's Hospital (A.D., R.R.A., V. W.), London W.2.; Sherrington School of Physiology and Department of Biochemistry, St. Thomas'Hospital (U.B., B.G., M.T.J.), London S.E.I.; the Department of Medicine II, St. George's Hospital Medical School (J.S.J.), London S.W.17., England; and the Department of Medicine, Erasmus University (S.W.J.L.), Rotterdam, The Netherlands

Address all correspondance and requests for reprints to Anne Dornhorst, M.D., Veterans Administration Medical Center, Medical Service (111-W), 10701 East Boulevard, Cleveland, Ohio 44106.

It has previously been reported that sodium valproate (Epilim) lowers plasma ACTH levels in Nelson's syndrome. This report describes further experience with its use. Ten patients with Nelson's syndrome were treated with sodium valproate (600–1200 mg/day) for 5–32 weeks. Plasma ACTH was measured by cytochemical methods and RIA. Initial treatment for 5–12 weeks significantly (P < 0.005) lowered plasma ACTH from a pretreatment mean of 2460 ± 1870 ng/liter to 480 ± 330 ng/liter, and the ACTH circadian rhythm was restored in two patients. On discontinuing treatment, plasma ACTH levels remained suppressed for 3 weeks and rose to pretreatment values in 5–12 weeks. Two patients'plasma ACTH levels failed to show a second response to treatment, while a third patient had a favorable second response to treatment over 32 weeks. In six patients, skin pigmentation lightened with treatment, and in one patient, a reduction in size of a pituitary microadenoma, demonstrated radiographically, occurred with treatment. {gamma}-Aminobutyric acid and sodium valproate were shown to be ineffective in inhibiting ACTH secretion from cultured pituitary tumor cells from a patient with Nelson's syndrome.

The results show that sodium valproate is effective in some cases of Nelson's syndrome. We suggest that it reduces the hypersecretion of ACTH by enhancing {gamma}-aminobutyric acid function in the hypothalamus, thereby inhibiting the release of corticotropin-releasing factor. (J Clin Endocrinol Metab 56: 985, 1983)

* This work was supported by Labaz (Sanofi U.K. Ltd.).

Received July 8, 1982.




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