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Heterogeneous natural history of Addison’s disease: mineralocorticoid deficiency may predominate

Lookup NU author(s): Sophie Howarth, Dr Catherine Napier, Professor Simon PearceORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 The authors.Autoimmune Addison’s disease (AAD) is defined as primary adrenal insufficiency due to immune-mediated destruction of the adrenal cortex. This destruction of steroid-producing cells has historically been thought of as an irreversible process, with linear progression from an ACTH-driven compensated phase to overt adrenal insufficiency requiring lifelong glucocorticoid replacement. However, a growing body of evidence suggests that this process may be more heterogeneous than previously thought, with potential for complete or partial recovery of glucocorticoid secretion. Although patients with persistent mineralocorticoid deficiency despite preserved or recovered glucocorticoid function are anecdotally mentioned, few well-documented cases have been reported to date. We present three patients in the United Kingdom who further challenge the long-standing hypothesis that AAD is a progressive, irreversible disease process. We describe one patient with a 4-year history of mineralocorticoid-only Addison’s disease, a patient with spontaneous recovery of adrenal function and one patient with clinical features of adrenal insufficiency despite significant residual cortisol function. All three patients show varying degrees of mineralocorticoid deficiency, suggesting that recovery of zona fasciculata function in the adrenal cortex may occur independently to that of the zona glomerulosa. We outline the current evidence for heterogeneity in the natural history of AAD and discuss possible mechanisms for the recovery of adrenal function.

Publication metadata

Author(s): Howarth S, Giovanelli L, Napier C, Pearce SH

Publication type: Article

Publication status: Published

Journal: Endocrine Connections

Year: 2023

Volume: 12

Issue: 1

Print publication date: 01/01/2023

Online publication date: 18/11/2022

Acceptance date: 18/11/2022

Date deposited: 28/03/2023

ISSN (electronic): 2049-3614

Publisher: BioScientifica Ltd.


DOI: 10.1530/EC-22-0305


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Funder referenceFunder name
G0701632Medical Research Council (MRC)
MR/J002526/1Medical Research Council (MRC)