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Consensus statement on the diagnosis, treatment and follow‐up of patients with primary adrenal insufficiency
Open accessAbstract
Primary adrenal insufficiency ( PAI ), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow‐up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21‐hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life‐threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow‐up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self‐adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow‐up.
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“If these diagnoses are excluded, a CT scan of the adrenals may reveal evidence of adrenal infiltrative processes or metastases.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [181]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most common causes of PAI are autoimmune destruction of the adrenal cortex in adults and CAH in children.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [181]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These etiologies can be screened for using 21-hydroxylase antibodies and a baseline serum 17hydroxyprogesterone level.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [181]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“A daily glucocorticoid dose equivalent to prednisolone ≥ 5 mg, for longer than 1 month represents an adrenal suppressive dosein a proportion of adults [3, 4].”
From Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency (2020) · cites this paper as [3]
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“Therapeutic patient education is recommended by two international consensus statements on the management of PAI.18,64”
From Adrenal crisis: prevention and management in adult patients (2019) · cites this paper as [64]
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“the standard dose (250 μg) corticotropin (1–24 ACTH) test (SDCT) represents the gold standard dynamic test for PAI, while the insulin tolerance test (ITT) is the gold standard if SAI is suspected [1–5].”
In the citing paper
“Although morning serum cortisol concentrations are helpful to determine hypothalamic-pituitary-adrenal axis function, the evidence in the literature is as yet insufficient to support the use of basal cortisol concentrations alone in order to either rule out or confirm AI [1–5].”
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Self-citation
Metadata
- Authors
- Husebye, E. S., Allolio, B., Arlt, W., Badenhoop, K., Bensing, S., Betterle, C., Falorni, A., Gan, E. H., Hulting, A. ‐., Kasperlik‐Zaluska, A., Kämpe, O., Løvås, K., Meyer, G., & Pearce, S. H.
- Affiliations
- Haukeland University Hospital (NO)
- Universitätsklinikum Würzburg (DE)
- University of Birmingham (GB)
- Goethe University Frankfurt (DE)
- Karolinska Institutet (SE)
- University of Padua (IT)
- University of Perugia (IT)
- Newcastle University (GB)
- Department of Endocrinology Medical Center of Postgraduate Education Warsaw Poland
- Uppsala University (SE)
- Corresponding author
- Husebye, E. S.
- ORCID
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2013-12-16
- Volume
- 275
- Issue
- 2
- Pages
- 104-115
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- OpenAlex
- W2123534035
- Semantic Scholar
- 2601afd1dd34510db2d279e5db17be74242fad23
- Cited by
- 403
- References
- 34
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 32 · 2023: 24 · 2022: 26 · 2021: 30 · 2020: 43 · 2019: 27 · 2018: 31 · 2017: 40 · 2016: 35 · 2015: 40 · 2014: 28 · 2013: 1
- FWCI
- 27.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- FP7 (201167)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Addison's disease, autoimmune adrenal insufficiency, 21-hydroxylase autoantibodies, adrenal crisis, hydrocortisone replacement, fludrocortisone, autoimmune disease comorbidity, diagnosis, follow-up, patient education
- MeSH terms
- Acute Disease, Addison Disease, Adrenal Cortex, Adrenal Insufficiency, Algorithms, Autoantibodies, Chronic Disease, Cortisone, Diagnosis, Differential, Drug Administration Schedule, Drug Interactions, Emergency Treatment, Europe, Female, Humans, Hydrocortisone, Male, Prednisolone, Pregnancy, Pregnancy Complications, Steroid 21-Hydroxylase, Autoimmunity
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