Time Course of 21-Hydroxylase Antibodies and Long-Term Remission of Subclinical Autoimmune Adrenalitis after Corticosteroid Therapy: Case Report

Abstract

Subclinical Addison's disease is characterized by the presence of adrenal autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21OHAb) with or without adrenal function failure. In our previous longitudinal study some patients with high titers of ACA and at stage 2 of subclinical adrenocortical failure showed disappearance of ACA with recovery of normal adrenocortical function after corticosteroid treatment for Graves' ophthalmopathy. To investigate whether corticosteroid-induced modification of the adrenal autoimmune markers can also involve 21OHAb and to evaluate whether the remission of subclinical adrenocortical failure can persist over a long period of time, we followed-up for 100 months the levels of 21OHAb and ACA as well as the metabolic markers of adrenal function in one patient with Graves' ophthalmopathy and at stage 2 of subclinical adrenocortical failure before and after corticosteroid therapy. A 34-yr-old woman with Graves' disease and active ophthalmopathy who was found to be positive for ACA and to have high PRA, low aldosterone levels, and normal basal ACTH and cortisol levels, but impaired cortisol response to ACTH was studied. The patient was treated with oral corticosteroid therapy for 6 months. After corticosteroid therapy, 21OHAb, initially positive, became negative in concomitance with the disappearance of ACA and the restoration of normal adrenal function. The disappearance of both 21OHAb and ACA and their prolonged absence during the follow-up suggest that corticosteroid treatment can induce long-term remission of subclinical adrenal insufficiency and prevent the onset of the clinical phase of the disease. Our pilot study may pave the way to future trials aimed at preventing the onset of the clinical signs of Addison's disease in ACA/21OHAb-positive patients.

Does recovery of adrenal function occur in patients with autoimmune Addison’s disease?

“…It is believed that Addison’s disease will only become clinically apparent if more than 90% of the adrenals are destroyed. Spontaneous remission of subclinical adrenocortical dysfunction can occur 10,11 . Clinically manifest autoimmune adrenocortical failure on the other hand is still considered to be a chronic, incurable disease leaving patients requiring lifelong glucocorticoid and mineralocorticoid replacement therapy (RT) with possible side effects of mild over‐replacement in the long term.…”

The natural history of autoimmune Addison’s disease from the detection of autoantibodies to development of the disease: a long-term follow-up study on 143 patients

“…However, sporadically ACA-positive patients at Stage 1-2 may improve to normal adrenal function, either spontaneously or after high doses of steroids (30). One reported patient remained in remission for more than 100 months after steroid treatment (31). In the present study, we have confirmed that the Stage 2 of adrenal cortical dysfunction at the beginning of the follow-up is an important and independent risk factor for the progression to AAD for all the patients with APS-1 or APS-2/APS-4 ( Fig.…”

Insuficiência adrenal primária no adulto: 150 anos depois de Addison

“…Da mesma forma, a zona fasciculada pode ser protegida do ataque linfocitário por um período mais longo devido às altas concentrações de hormônios corticosteróides produzidas localmente e/ou maior habilidade de regeneração (10). Remissão dos sinais bioquímicos de disfunção adrenal pode ser observada em até 50% dos pacientes com DA potencial ou no estágio 1, associada ao desaparecimento ou negativação dos 21OHAc (62,69).…”

“…Progressos nos estudos do papel dos linfócitos T e a identificação dos auto-antígenos reconhecidos pelos seus receptores poderão levar, no futuro, ao desenvolvimento de uma vacina efetiva (10). Reversibilidade da disfunção adrenal auto-imune também pode ser induzida por corticoterapia em dose imunossupressora, apesar de títulos elevados de ACA (1:32 a 1:64), mesmo em pacientes em estágios mais avançados da insuficiência adrenocortical subclínica (69). Deve-se ressaltar que o tratamento imunossupressor da doença adrenal auto-imune ainda não está bem estabelecido, não sendo indicado, portanto, como tratamento de rotina desta doença.…”