Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity inhibition in vivo.
Adrenal autoantibodies (ACA) are markers of adrenal cortex involvement in idiopathic Addison's disease. Recently the 21-hydroxylase (21-OH) enzyme has been discovered to be the major autoantigen of the ACA. A potential role of these antibodies in determining adrenal failure by inhibition of the 21-OH has been recently postulated. To test this hypothesis, cortisol and aldosterone (final products of adrenal steroid synthesis) and 17-hydroxyprogesterone (17-OH-progesterone) (as a marker of 21-OH impairment) have been investigated in baseline conditions and after ACTH (1-24) stimulation test in a group of 42 patients positive for both ACA and 21-OH autoantibodies. Patients were divided into five groups according to the stages (0-4) of adrenal failure. With progression toward overt Addison's disease, baseline 17-OH-progesterone, cortisol, and aldosterone remained almost unchanged but with impairment of their responses to ACTH (1-24) stimulation. The 17-OH-progesterone/cortisol ration remained normal both in basal conditions and after stimulation at stages 0-3. At stage 4 (overt Addison's disease), this ratio increased in baseline condition with no changes after ACTH (1-24), probably because of persistent 17-OH-progesterone gonadal production. In conclusion, there was a progressive and concomitant impairment of the synthesis of all steroids tested over various phases of adrenal failure. The pattern of response of the 17-OH-progesterone/cortisol ratio to ACTH stimulation in patients with 21-OH autoantibodies was not consistent with the autoantibodies inhibiting the 21-OH activity. This suggests that the inhibiting effect of 21-OH autoantibodies on 21-OH activity is not usually evident in vivo.
Boscaro
M
M
Division of Endocrinology, University of Padova, Italy.
Betterle
C
C
Volpato
M
M
Fallo
F
F
Furmaniak
J
J
Rees Smith
B
B
Sonino
N
N
D000307:Adrenal Gland Diseases / Q000097:blood* / Q000503:physiopathology; D000311:Adrenal Glands / Q000276:immunology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000097:blood* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors*
D001323:Autoantibodies; D006728:Hormones; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D012083:Renin