adrenomedullin and Addison-Disease

Adrenomedullin (AM) is a recently purified hypotensive peptide and its encoding gene has been sequenced from a human pheochromocytoma. High levels of AM have been shown in Addison's disease (AD). X-linked adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) is a peculiar adrenal insufficiency due to an accumulation of very-long chain fatty acid in adrenal cells and it is very often associated with a devastating demyelination of the central nervous system.. We studied the AM plasma levels of 22 patients with ALD/AMN (18 with hypoadrenalism, ALDa, and 4 with normal adrenal function, ALDb) and compared them with 18 males with classical AD and 16 normal male subjects. All patients with hyposurrenalism were studied before treatment with hydrocortisone.. Both patients with ALD/AMN and AD showed increased levels of AM and all of them showed a significant difference from the control group (p < 0.0001). The plasma renin activity was higher in all patient groups than in the control group (p <0.001 ALDa, ALDb and AD vs. control group). The aldosterone levels were higher in ALDa and ALDb groups than AD (ALDa vs. AD p < 0.01; ALDb vs. control group p < 0.05; AD vs. controls p < 0.01). ACTH plasma levels were higher in ALDa and AD than ALDb and the control group (ALDa vs. AD not significant while ALDa and AD vs. control p <0.0001).. Our data indicate that plasma AM levels in ALDa, ALDb and AD are higher than controls. These results were previously described in untreated AD. While classical AD patients show complete adrenal insufficiency (both mineralocorticoid and glucocorticoid defects), ALD/AMN patients show a less compromised glomerular function, indicating that AM is not completely correlated with mineralocorticoid insufficiency, and that the exact mechanism responsible for the increased AM levels in ALD/AMN is still unknown.

Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Adrenoleukodystrophy; Adrenomedullin; Adult; Case-Control Studies; Child; Humans; Male; Middle Aged; Peptides

A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure.. Plasma AM levels were measured in patients with proven Addison's disease using a specific radioimmunoassay and compared to those in healthy normotensive subjects.. Eighteen patients with Addison's disease (10 men and eight women; ages 21 to 72 years) and 21 healthy control subjects (13 men and eight women; ages 20 to 71 years) were enrolled in the study. All patients were studied under basal conditions and 10 were reassessed following corticosteroid treatment.. All patients with Addison's disease showed increased levels of AM compared to the control group. Mean plasma AM levels were correspondingly higher in patients with Addison's disease than in normal subjects (102.1 +/- 33.4 (SD) ng/l versus 13.7 +/- 6.1 ng/l; P < 0.0001). In 10 patients studied after corticosteroid treatment, plasma AM levels were significantly reduced (P < 0.0001: 110.3 +/- 35.8 ng/l versus 32.4 +/- 10.3 ng/l) after 2 weeks of treatment. A weak correlation (r = 0.458; P = 0.048) was observed between systolic blood pressure and plasma AM concentrations in all patients with Addison's disease.. These results indicate a consistent but reversible increase of adrenomedullin in patients with Addison's disease.

Topics: Addison Disease; Adrenomedullin; Adult; Aged; Blood Pressure; Female; Fludrocortisone; Humans; Hydrocortisone; Male; Middle Aged; Mineralocorticoids; Peptides; Radioimmunoassay; Regression Analysis