Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency.
Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.
Boscaro
M
M
Division of Endocrinology, University of Padova, Italy.
Betterle
C
C
Sonino
N
N
Volpato
M
M
Paoletta
A
A
Fallo
F
F
D019326:17-alpha-Hydroxyprogesterone; D000224:Addison Disease / Q000276:immunology; D000311:Adrenal Glands / Q000276:immunology / Q000503:physiopathology*; D000309:Adrenal Insufficiency / Q000276:immunology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone; D003366:Cosyntropin; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D007037:Hypothyroidism / Q000276:immunology / Q000503:physiopathology; D007700:Kinetics; D008875:Middle Aged; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000503:physiopathology
D001323:Autoantibodies; D006908:Hydroxyprogesterones; D003366:Cosyntropin; D000450:Aldosterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone