naloxone and Nelson-Syndrome

The effect of a high (5.4 mg/h) and a low (0.8 mg/h) dose of naloxone (i.v. over a period of 90 min) on ACTH secretion was compared with placebo in patients with Addison's disease, congenital adrenal hyperplasia, Cushing's disease or Nelson's syndrome. In seven patients with primary adrenal insufficiency the high dose of naloxone provoked a significant increase of plasma ACTH concentrations (P less than 0.02) whereas the low dose of naloxone failed to influence ACTH secretion. In six patients with ACTH dependent Cushing's disease or Nelson's syndrome both doses failed to alter plasma ACTH levels. These results support the concept of inhibitory delta- or kappa-opiate receptors in the regulation of ACTH secretion. In patients with Cushing's disease or Nelson's syndrome ACTH secretion is insensitive to naloxone, presumably because of an autonomous pituitary adenoma or hypothalamic derangement.

Topics: Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Naloxone; Nelson Syndrome

Topics: Adult; beta-Endorphin; Cognition; Cushing Syndrome; Emotions; Endorphins; Humans; Middle Aged; Naloxone; Nelson Syndrome; Nociceptors

Topics: Acromegaly; Addison Disease; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Lipotropin; Diethylstilbestrol; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Nelson Syndrome; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prolactin

ACTH excretion by cultured nonenzymatically dispersed pituitary tumor cells from a patient with Nelson's syndrome was studied. Hormone release was suppressed by 74 +/- 6% by the addition of 1 microM of the met-enkephalin analog FK 33824, while naloxone (1 microM) stimulated ACTH release by 70 +/- 5%. Somatostatin, dexamethasone, bromocriptine, and cyproheptadine in a concentration of 1 microM each inhibited ACTH release by 25 +/- 2%, 35 +/- 2%, 52 +/- 2%, and 61 +/- 4%, respectively, while lysine vasopressin (0.1 microM) and dibutyryl cAMP (5 mM) stimulated ACTH release by 112 +/- 8% and 220 +/- 4%, respectively. In conclusion, it was shown that the stimuli mentioned above directly affect ACTH secretion by the pituitary tumor cells. The inhibitory action of the met-enkephalin analog and the stimulatory action of naloxone on ACTH secretion make the presence of opiate receptors on this type of tumor likely.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cells, Cultured; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalins; Female; Hormones; Humans; Naloxone; Nelson Syndrome; Pituitary Neoplasms

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.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Humans; Hydrocortisone; Middle Aged; Naloxone; Nelson Syndrome; Pituitary Neoplasms; Valproic Acid