Autoantibodies to 21-hydroxylase as a diagnostic marker of primary autoimmune adrenal insufficiency, including at its potential and latent stages

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Rationale: In Russia, assessment of anti-P450c21 antibodies (AB) in the diagnosis of autoimmune adrenal insufficiency (AAI) has not been commonly used, and the disease screening has not been implemented.

Aims: 1)  To determine the sensitivity and specificity of anti-P450c21 AB determination in the AAI diagnosis; 2)  To estimate the prevalence of anti-P450c21 AB carriage in patients without AAI.

Materials and methods: Anti-P450c21 AB were assessed in 40  patients (group  1) with manifest AAI; 171  patients without established diagnosis of AAI, including 113  subjects with autoimmune thyroid disorders or type 1 diabetes mellitus (AID, group 2); 25 carriers of AB markers of thyroid AID and/or type  1 diabetes mellitus without any target organ dysfunctions (group 3); 33 patients with non-autoimmune endocrine disorders (group  4), and 25 healthy individuals (group 5).

Results: Determination of anti-P450c21 AB for the diagnosis of AAI had 95%  sensitivity, with specificity of 100%, predictive value of a positive result of 100%, and predictive value of a negative result 92.6%. Anti-P450c21 AB were inversely correlated with the duration of glucocorticoid replacement therapy (r=-0.222, p<0.05). High levels of anti-P450c21 AB were found in 4 (3.5%) patients of group  2; based on the results of additional hormonal testing, 50%  cases were diagnosed with the latent stage of the disease and 50% cases with the potential stage.

Discussion: The sensitivity of the anti-P450c21 AB determination for AAI diagnosis in our study was higher, than in the works by other authors. We have confirmed a  time-related reduction of anti-P450c21 AB levels, whereby the strength of the correlation was higher in the subgroups with autoimmune polyendocrine syndrome type  II and, to a greater extent, autoimmune polyendocrine syndrome type I. This might be related to their different pathogenesis, with an abnormality of central immune tolerance in autoimmune polyendocrine syndrome type I and that of peripheral immune tolerance in autoimmune polyendocrine syndrome type II. According to our data, in 50% of cases, the development of AAI was preceded by the manifestation of other AIDs (in 15% of cases being multiple). Among all patients with no AAI diagnosis at the study entry, increased anti-P450c21 AB levels were found exactly in those with pre-existing AID. Thus, we have confirmed the feasibility of AAI screening primarily in a cohort of patients with other AID (especially multiple) belonging to the risk group.

Conclusion: The determination of blood anti-P450c21 AB is a highly sensitive and highly specific method to diagnose AAI. The frequency of anti-P450c21 AB detection might depend on the duration of glucocorticoid treatment. Screening for early AAI stages is relevant primarily in the risk groups with multiple autoimmune disorders.

About the authors

N. F. Nuralieva

Endocrinology Research Centre

Author for correspondence.
ORCID iD: 0000-0001-6876-3336

Nurana F. Nuralieva – Research Fellow, Department of Therapeutic Endocrinology

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

M. Yu. Yukina

Endocrinology Research Centre

ORCID iD: 0000-0002-8771-8300

Marina Yu. Yukina – MD, PhD, Leading Research Fellow, Department of Therapeutic Endocrinology

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

E. A. Troshina

Endocrinology Research Centre

ORCID iD: 0000-0002-8520-8702

Ekaterina A. Troshina – MD, PhD, Professor, Corresponding Member of RAS, Head of Department of Therapeutic Endocrinology

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

N. M. Malysheva

Endocrinology Research Centre

ORCID iD: 0000-0001-7321-9052

Natalya M. Malysheva – PhD (in Biol.), Leading Research Fellow, Clinical and Diagnostic Laboratory

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

L. V. Nikankina

Endocrinology Research Centre

ORCID iD: 0000-0002-3199-4998

Larisa V. Nikankina – MD, PhD, Acting Head of Clinical and Diagnostic Laboratory

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation


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Copyright (c) 2020 Nuralieva N.F., Yukina M.Y., Troshina E.A., Malysheva N.M., Nikankina L.V.

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