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Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism

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Abstract

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease, β-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.

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Fallo, F., Boscaro, M., Sonino, N. et al. Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism. J Endocrinol Invest 11, 261–265 (1988). https://doi.org/10.1007/BF03350149

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