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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 / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

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1437-4331
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Volume 56, Issue 6

Issues

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

Abstract

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

References

  • 1.

    Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014;275:104–15.CrossrefWeb of SciencePubMedGoogle Scholar

  • 2.

    Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 2002;23:327–64.CrossrefPubMedGoogle Scholar

  • 3.

    Betterle C, Zanchetta R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed 2003;74:9–33.PubMedGoogle Scholar

  • 4.

    Betterle C, Garelli S, Presotto F, Furmaniak J. From appearance of adrenal autoantibodies to clinical symptoms of Addison’s disease: natural history. Front Horm Res 2016;46:133–45.Web of SciencePubMedCrossrefGoogle Scholar

  • 5.

    Coco G, Dal Pra C, Presotto F, Albergoni MP, Canova C, Pedini B, et al. Estimated risk for developing autoimmune Addison’s disease in patients with adrenal cortex autoantibodies. J Clin Endocrinol Metab 2006;91:1637–45.PubMedCrossrefGoogle Scholar

  • 6.

    Napier C, Pearce SH. Autoimmune Addison’s disease. Presse Med 2012;41:e626–35.PubMedCrossrefGoogle Scholar

  • 7.

    Betterle C, Scalici C, Presotto F, Pedini B, Moro L, Rigon F, et al. The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J Endocrinol 1988;117:467–75.CrossrefPubMedGoogle Scholar

  • 8.

    Barker JM, Ide A, Hostetler C, Yu L, Miao D, Fain PR, et al. Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison’s disease in a high-risk population. J Clin Endocrinol Metab 2005;90: 128–34.CrossrefGoogle Scholar

  • 9.

    Saenger P, Levine LS, Irvine WJ, Gottesdiener K, Rauh W, Sonino N, et al. Progressive adrenal failure in polyglandular autoimmune disease. J Clin Endocrinol Metab 1982;54:863.PubMedCrossrefGoogle Scholar

  • 10.

    Ketchum CH, Riley WJ, Maclaren NK. Adrenal dysfunction in asymptomatic patients with adrenocortical autoantibodies. J Clin Endocrinol Metab 1984;58:1166–70.CrossrefPubMedGoogle Scholar

  • 11.

    Ahonen P, Miettinen A, Perheentupa J. Adrenal and steroidal cell antibodies in patients with autoimmune polyglandular disease type I and risk of adrenocortical and ovarian failure. J Clin Endocrinol Metab 1987;64:494–500.CrossrefPubMedGoogle Scholar

  • 12.

    Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Greggio NA, et al. I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997;82:932–8.PubMedGoogle Scholar

  • 13.

    Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Zanchetta R, et al. II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997;82:939–42.PubMedGoogle Scholar

  • 14.

    Laureti S, De Bellis A, Muccitelli VI, Calcinaro F, Bizzarro A, Rossi R, et al. Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison’s disease. J Clin Endocrinol Metab 1998;83:3507–11.PubMedGoogle Scholar

  • 15.

    Baker PR, Nanduri P, Gottlieb PA, Yu L, Klingensmith GJ, Eisenbarth GS, et al. Predicting the onset of Addison’s disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies. Clin Endocrinol (Oxf) 2012;76:617–24.CrossrefPubMedGoogle Scholar

  • 16.

    del Pilar Larosa M, Chen S, Steinmaus N, Macrae H, Guo L, Masiero S, et al. A new ELISA for autoantibodies to steroid 21-hydroxylase. Clin Chem Lab Med 2018;56:933–8.CrossrefPubMedGoogle Scholar

  • 17.

    Betterle C, Rossi A, Dalla Pria S, Artifoni A, Pedini B, Gavasso S, et al. Premature ovarian failure: autoimmunity and natural history. Clin Endocrinol 1993;39:35–43.CrossrefGoogle Scholar

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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