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Two patients with Nelson's syndrome and one patient after bilateral adrenalectomy for Cushing's disease, without any evidence of Nelson's syndrome, were studied with respect to the effect of hydrocortisone, naloxone and valproic acid (a GABA transaminase inhibitor) on ACTH secretion. Hydrocortisone suppressed plasma ACTH concentrations to normal in the patient without Nelson's syndrome, but failed to do so in the two patients with Nelson's syndrome. Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelson's syndrome, but produced no change in the patient without Nelson's syndrome. Secretion of ACTH may thus be influenced by both opiate peptide and by gamma aminobutyric acid, as well as by the cortisol concentration, these agents may act at different sites to inhibit ACTH release by the tumour.
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