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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

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Volume 56, Issue 6


The natural history of autoimmune Addison’s disease with a non-classical presentation: a case report and review of literature

Jacopo Manso / Raffaele Pezzani / Riccardo Scarpa / Nicoletta Gallo / Corrado Betterle
Published Online: 2018-02-26 | DOI: https://doi.org/10.1515/cclm-2017-1108


Autoimmune Addison’s disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto’s thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.

Keywords: 21-hydroxylase autoantibodies; Addison’s disease; adrenal cortex autoantibodies; autoimmune polyglandular syndrome; Hashimoto’s thyroiditis; natural history


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About the article

Corresponding author: Prof. Corrado Betterle, MD, Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Via Ospedale Civile 105, 35128 Padova, Padova, Italy, Phone: (+39)049.8214273, Fax: (+39)049.657391

Received: 2017-11-27

Accepted: 2018-01-24

Published Online: 2018-02-26

Published in Print: 2018-05-24

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 896–900, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-1108.

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