Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies.

Abstract

Idiopathic Addison's disease is a chronic organ-specific autoimmune disorder with a long subclinical period characterized only by the presence of adrenal autoantibodies (AA) with or without adrenal function failure. The aim of this longitudinal study was to evaluate the behavior of AA using, an indirect fluorescence method, and adrenal function in 20 AA-positive and 50 AA-negative patients screened by an investigation of a large population of organ-specific autoimmune disease patients without clinical Addison's disease. As controls, 100 normal age-matched subjects were tested only once. In the 20 AA-positive and 50 negative patients, AA and adrenal functional tests were evaluated every 4 months for 5 yr. The AA-positive patients were grouped into 5 adrenal functional stages, specifically: stage 0, normal adrenal function; stage 1, high PRA and low (or normal) aldosterone levels alone; stage 2, along with impaired cortisol response to ACTH, stage 3, along with increased ACTH levels; and stage 4, clinically overt Addison's disease. On the basis of the behavior of AA, the 20 positive patients were grouped as follows: group A, 11 patients with AA titer of 1:8 or higher at the first observation and persistently AA positive in subsequent observations, with titers ranging from 1:8 to 1:64; group B, 6 patients with initial AA titers of 1:8 or lower and AA disappearance in subsequent observations; and group C, 3 patients with AA titer of 1:32 or higher, undergoing corticosteroid therapy after the start of the study and showing AA disappearance in subsequent observations. With respect to adrenal function in group A, 2 patients initially in stage 1 and 1 patient initially in stage 2 did not progress to the upper stages, whereas 5 patients initially in stage 0 and 3 initially in stage 1 progressed subsequently to the upper stages, in 2 cases reaching overt clinical Addison's disease (stage 4). On the other hand, all of the patients of group B showed both a spontaneous disappearance of AA and recovery of adrenal function during the study span. Also, the 3 patients of group C showed disappearance of AA after corticosteroid therapy with recovery of adrenal function. None of the 50 patients who were initially AA negative became AA positive subsequently or showed impairment of adrenal function. We reached the following conclusions. 1) AA, even if present initially in some subjects without clinical Addison's disease, can subsequently disappear. 2) Restoration of adrenal function after disappearance of AA indicates that a spontaneous remission of subclinical adrenocortical failure can occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal and ovarian autoimmunity

“…After several months or years, a dysfunction of the zona fasciculata becomes evident which is manifested at first by a decrease of the plasma cortisol response to adrenocorticotropic hormone (ACTH) (stage 2), followed by an increased plasma ACTH level (stage 3) and finally by a decreased plasma cortisol level and overt clinical symptoms (stage 4) (34). Subsequently, it has been reported that ACA in some patients without clinical AAD can disappear spontaneously or after corticosteroid therapy with restoration of the previous impaired adrenal function (35). However, recent follow-up studies of 58 ACA-positive patients (children and adults) indicated that ACA were persistent markers of progression towards overt or subclinical AAD (31,32).…”

“…Recently, the laboratory diagnosis of AAD has been enriched by use of specific recombinant autoantigens. Two different immunoprecipitation assays for the detection of autoantibodies to 21-OH (21-OH Abs) have been developed, one based on 35 S-labeled 21-OH produced in an in vitro transcriptiontranslation system (56,70), the other based on 125 Ilabeled recombinant 21-OH produced in yeast (59). Immunoprecipitation assays based on 35 S-21-OH are highly specific and sensitive with a good reproducibility but there are limitations associated with the use of DNA and 35 S-labeled material.…”

“…Two different immunoprecipitation assays for the detection of autoantibodies to 21-OH (21-OH Abs) have been developed, one based on 35 S-labeled 21-OH produced in an in vitro transcriptiontranslation system (56,70), the other based on 125 Ilabeled recombinant 21-OH produced in yeast (59). Immunoprecipitation assays based on 35 S-21-OH are highly specific and sensitive with a good reproducibility but there are limitations associated with the use of DNA and 35 S-labeled material. Assays based on 21-OH labeled with 125 I, however, in addition to high specificity, sensitivity and a good precision have the added advantage of being convenient and easy to use in routine laboratories.…”

Antiphospholipid syndrome, adrenal failure, dilated cardiomyopathy and chronic hepatitis: an unusual manifestation of multiorgan autoimmune injury?

“…Fluorescein isothiocyanate-conjugated rabbit antihuman immunoglobulin G (IgG) serum (Dako, Milan, Italy) diluted 1:40, was used to detect the presence of ACA reacting with adrenal antigens. Complement-fixing ACA were detected with rabbit fluorescein isothiocyanate serum antihuman C3 (Dako) at a 1:40 dilution as previously described (6). Activated partial thromboplastin time was prolonged and did not normalize after the addition of normal plasma thus revealing that it was not caused by insufficient and/or altered production of coagulation factors.…”

“…ACA are regarded as sensitive markers of the autoimmune form of adrenal failure (6,14). Although their role in the primary pathogenic response is unclear, it is likely that they arise as a consequence of T-cell-mediated tissue damage, which seems to be a major event in the pathogenesis of adrenal failure.…”