naloxone and Hyperaldosteronism

Endogenous opioids may normally modulate the function of the hypothalamo-pituitary-adrenal axis. We investigated whether opioid peptides play any role on aldosterone secretion in dexamethasone-suppressible hyperaldosteronism (DSH). Clinical and hormonal effects of i.v. administration of naloxone (10 mg as a bolus) in two siblings affected by this disease and in eight normal volunteers were studied. In normals, naloxone caused a significant increase in plasma cortisol compared with placebo, an insignificant increase in ACTH and no change in plasma renin activity (PRA) and aldosterone level. In DSH patients there was a slight increase in plasma cortisol, no change in PRA and a marked rise of aldosterone level. In five normals retested after dexamethasone 2 mg, baseline ACTH and cortisol were reduced and no response to naloxone was observed compared to naloxone alone. After dexamethasone, aldosterone levels were suppressed in DSH patients and unchanged in normals, and did not respond to naloxone in any case. In conclusion, naloxone may increase the responsiveness of adrenal zona fasciculata to physiological levels of ACTH in normals, since the slight increase in ACTH seems inadequate to explain per se the marked cortisol elevation. The marked aldosterone rise after naloxone indicates an underlying adrenal rather than pituitary abnormality in patients with DSH, and possibly implicates endogenous opioids.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Dexamethasone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Naloxone; Pituitary-Adrenal System

In order to elucidate whether pituitary peptides other than ACTH which are derived from the proopiomelanocortin (POMC) are involved for aldosterone secretion in primary aldosteronism, we administered ovine corticotropin releasing factor (CRF), beta-endorphin and naloxone to seven patients with aldosterone producing adenoma. One hundred micrograms of CRF produced an augmented aldosterone response in patients with aldosteronism, while 500 micrograms of beta-endorphin infusion failed to cause any significant changes in neither normal subjects nor patients. An opioid antagonist, naloxone (10 mg, iv) produced no noticeable change in plasma aldosterone in normal subjects, while it caused a slight increase in patients with primary aldosteronism. Plasma cortisol increased to a similar degree in response to CRF and naloxone in normal subjects and patients. In three patients with isolated ACTH deficiency, neither aldosterone nor cortisol responded to these stimuli. The present results indicate that POMC-derived pituitary peptides other than ACTH are unlikely to participate in the aldosterone secretion in normal subjects or in patients with primary aldosteronism.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Aldosterone; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Injections, Intravenous; Male; Middle Aged; Naloxone; Pituitary Hormones; Pro-Opiomelanocortin

Endogenous opioids have been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To investigate this issue, the opiate antagonist naloxone was administered to 8 normals and 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. In normals, APA, and IHA, naloxone caused a significant increase in plasma cortisol and no change in ACTH, renin activity (PRA), and aldosterone levels. All subjects were retested after dexamethasone 2 mg. ACTH and cortisol were reduced and PRA was unchanged without modifications after naloxone. Baseline aldosterone was unaltered in all. While normals and APA failed to show any aldosterone response to naloxone under dexamethasone, IHA patients demonstrated a significant decrease. beta-Endorphin concentrations were in the normal range before and after dexamethasone. In normals as well as in APA and IHA, naloxone may act directly on the adrenal cortex increasing zona fasciculata responsiveness to physiological levels of ACTH. The decrease of aldosterone induced by naloxone in IHA under dexamethasone may be due to an intra-adrenal opioid control of zona glomerulosa in this disorder.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Dexamethasone; Humans; Hydrocortisone; Hyperaldosteronism; Naloxone; Renin

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. beta-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.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Adult; beta-Endorphin; Dexamethasone; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Naloxone