Adrenal Steroidogenesis after B Lymphocyte Depletion Therapy in New-Onset Addison's Disease
Open accessAbstract
Context: A diagnosis of Addison's disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality as well as a risk of unexpected adrenal crisis. Objective: The objective of the study was to determine whether immunomodulatory therapy at an early stage of autoimmune Addison's disease could lead to preservation or improvement in adrenal steroidogenesis. Design and Intervention: This was an open-label, pilot study of B lymphocyte depletion therapy in new-onset idiopathic primary adrenal failure. Doses of iv rituximab (1 g) were given on d 1 and 15, after pretreatment with 125 mg iv methylprednisolone. Patients and Main Outcome Measures: Six patients (aged 17–47 yr; four females) were treated within 4 wk of the first diagnosis of idiopathic primary adrenal failure. Dynamic testing of adrenal function was performed every 3 months for at least 12 months. Results: Serum cortisol levels declined rapidly and were less than 100 nmol/liter (3.6 μg/dl) in all patients by 3 months after B lymphocyte depletion. Serum cortisol and aldosterone concentrations remained low in five of the six patients throughout the follow-up period. However, a single patient had sustained improvement in both serum cortisol [peak 434 nmol/liter (15.7 μg/dl)] and aldosterone [peak 434 pmol/liter (15.7 ng/dl)] secretion. This patient was able to discontinue steroid medications 15 months after therapy and remains well, with improving serum cortisol levels 27 months after therapy. Conclusion: New-onset autoimmune Addison's disease should be considered as a potentially reversible condition in some patients. Future studies of immunomodulation in autoimmune Addison's disease may be warranted.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
At diagnosis, most patients with primary adrenal insufficiency retain a certain cortisol production.
“At diagnosis, most PAI patients retain a certain cortisol production (176).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [176]
The Steroidogenic function section reports measurable peak serum cortisol at first diagnosis in the six studied patients, supporting residual cortisol production in this group. But the study enrolled only six people with newly diagnosed idiopathic primary adrenal failure; it does not establish that most patients with primary adrenal insufficiency retain cortisol production at diagnosis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTreatment of newly diagnosed autoimmune primary adrenal insufficiency patients with rituximab and established primary adrenal insufficiency patients with depot tetracosactide has demonstrated that regeneration of cortisol production is possible.
“Treatment of newly diagnosed autoimmune PAI patients with rituximab (176) and established PAI patients with depot tetracosactide (177) has demonstrated that regeneration of cortisol production is possible.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [176]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
Edwards, J. C. W., Szczepański, L., Szechiński, J., Filipowicz-Sosnowska, A., Emery, P., Close, D. R., Stevens, R. M., & Shaw, T. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032534 · Cited by 2,623 · see citing works
Rituximab, B-lymphocyte depletion, and preservation of beta-cell function
Pescovitz, M. D., Greenbaum, C. J., Krause-Steinrauf, H., Becker, D. J., Gitelman, S. E., Goland, R., Gottlieb, P. A., Marks, J. B., McGee, P. F., Moran, A. M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904452 · Cited by 1,093 · see citing works
Premature Mortality in Patients with Addison’s Disease: A Population-Based Study
Bergthorsdottir, R., Leonsson-Zachrisson, M., Odén, A., & Johannsson, G. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0076 · Cited by 490 · see citing works
Bensing, S., Brandt, L., Tabaroj, F., Sjöberg, O., Nilsson, B., Ekbom, A., Blomqvist, P., & Kämpe, O. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03340.x · Cited by 242 · see citing works
Adrenal crisis in treated Addison's disease: a predictable but under-managed event
White, K., & Arlt, W. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0559 · Cited by 160 · see citing works
Immunologic endocrine disorders
Michels, A. W., & Eisenbarth, G. S. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.09.053 · Cited by 150 · see citing works
Autoimmune Addison disease: pathophysiology and genetic complexity
Mitchell, A. L., & Pearce, S. H. S. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.245 · Cited by 115 · see citing works
Self-citationRemission of subclinical adrenocortical failure in subjects with adrenal autoantibodies.
De Bellis, A., Bizzarro, A., Rossi, R., Paglionico, V. A., Criscuolo, T., Lombardi, G., & Bellastella, A. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.4.8473373 · Cited by 106 · see citing works
Øksnes, M., Bensing, S., Hulting, A.-L., Kämpe, O., Hackemann, A., Meyer, G., Badenhoop, K., Betterle, C., Parolo, A., Giordano, R., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1901 · Cited by 99 · see citing works
Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes
Waldron-Lynch, F., & Herold, K. C. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3402 · Cited by 92 · see citing works
Risk of hip fracture in Addison’s disease: a population-based cohort study
Björnsdottir, S., Sääf, M., Bensing, S., Kämpe, O., Michaëlsson, K., & Ludvigsson, J. F. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2011.02352.x · Cited by 82 · see citing works
Addison's disease in Africa—a teaching hospital experience
Soule, S. G. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00625.x · Cited by 81 · see citing works
Steroid 21-Hydroxylase Autoantibodies: Measurements with a New Immunoprecipitation Assay1
Tanaka, H., Pérez, M. S., Powell, M. J., Sanders, J. F., Sawicka, J. M., Chen, S., Prentice, L., Asawa, T., Betterle, C., Volpato, M., et al. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.5.3929 · Cited by 79 · see citing works
Self-citationAddison Disease in Adults: Diagnosis and Management
Chakera, A. J., & Vaidya, B. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.12.017 · Cited by 60 · see citing works
Self-citationAddison's disease. A staristical analysis of 566 cases and a study of the pathology
Guttman, P. (1930) · Medical Entomology and Zoology · Cited by 59 · see citing works
Steroid 21-Hydroxylase Autoantibodies: Measurements with a New Immunoprecipitation Assay
Tanaka, H. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.5.1440 · Cited by 57 · see citing works
Bellis, A. D., Falorni, A., Laureti, S., Perrino, S., Coronella, C., Forini, F., Bizzarro, E., Bizzarro, A., Abbate, G., & Bellastella, A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.2.675 · Cited by 51 · see citing works
Baker, P. R., Baschal, E. E., Fain, P. R., Triolo, T. M., Nanduri, P., Siebert, J. C., Armstrong, T. K., Babu, S. R., Rewers, M. J., Gottlieb, P. A., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0508 · Cited by 35 · see citing works
Partial recovery of adrenal function in a patient with autoimmune Addison’s disease
Smans, L. C. C. J., & ZELISSEN, P. M. J. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345623 · Cited by 26 · see citing works
Does recovery of adrenal function occur in patients with autoimmune Addison’s disease?
Smans, L. C. C. J., & ZELISSEN, P. M. J. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03944.x · Cited by 24 · see citing works
Spontaneously resolving Addison's disease
Chakera, A. J., & Vaidya, B. (2011) · QJM · doi:10.1093/qjmed/hcr162 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
1 of the 22 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Soule S 1999 Addison's disease in Africa-teaching hospital expe- rience. Clin Endocrinol (Oxf) 50:115-120
Cited by
Sorted by citations
Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
“Treatment of newly diagnosed autoimmune PAI patients with rituximab (176) and established PAI patients with depot tetracosactide (177) has demonstrated that regenerationof cortisol production ispossible.”
BackgroundHashimoto thyroiditis: Clinical and diagnostic criteria
Caturegli, P., Remigis, A. D., & Rose, N. R. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.01.007 · Cited by 1,082 · see citing works
Diagnosis and management of adrenal insufficiency
Bancos, I., Hahner, S., Tomlinson, J., & Arlt, W. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70142-1 · Cited by 467 · see citing works
Husebye, E. S., Pearce, S. H., Krone, N. P., & Kämpe, O. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00136-7 · Cited by 378 · see citing works
Self-citationHahner, S., Ross, R. J., Arlt, W., Bancos, I., Burger-Stritt, S., Torpy, D. J., Husebye, E. S., & Quinkler, M. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00252-7 · Cited by 223 · see citing works
Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults
Betterle, C., Presotto, F., & Furmaniak, J. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01079-6 · Cited by 139 · see citing works
An Update on Addison’s Disease
Barthel, A., Benker, G., Berens, K., Diederich, S., Manfras, B. J., Grüber, M., Kanczkowski, W., Kline, G. A., Kamvissi, V., Hahner, S., et al. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0804-2715 · Cited by 115 · see citing works
Autoimmune Addison's disease – An update on pathogenesis
Hellesen, A., Bratland, E., & Husebye, E. S. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.03.008 · Cited by 75 · see citing works
Therapy of adrenal insufficiency: an update
Falorni, A., Minarelli, V., & Morelli, S. (2012) · Endocrine · doi:10.1007/s12020-012-9835-4 · Cited by 56 · see citing works
Clues for early detection of autoimmune Addison's disease – myths and realities
Sævik, Å. B., Åkerman, A., Grønning, K., Nermoen, I., Valland, S. F., Finnes, T. E., Isaksson, M., Dahlqvist, P. M., Bergthorsdottir, R., Ekwall, O., et al. (2017) · Journal of Internal Medicine · doi:10.1111/joim.12699 · Cited by 59 · see citing works
Kumar, R., & Wassif, W. (2022) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2021-207895 · Cited by 56 · see citing works
Gan, E. H., MacArthur, K., Mitchell, A. L., Hughes, B. A., Perros, P., Ball, S. G., James, R. A., Quinton, R., Chen, S., Furmaniak, J., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2449 · Cited by 36 · see citing works
Self-citationResidual Corticosteroid Production in Autoimmune Addison Disease
Sævik, Å. B., Åkerman, A., Methlie, P., Quinkler, M. O., Jørgensen, A. P., Höybye, C., Dębowska, A., Nedrebø, B. G., Dahle, A. L., Carlsen, S., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa256 · Cited by 28 · see citing works
Napier, C., Gan, E. H., Mitchell, A. L., Gilligan, L. C., Rees, A., Moran, C., Chatterjee, K., Vaidya, B., James, R. A., Mamoojee, Y. H., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz287 · Cited by 24 · see citing works
Self-citationFuture Directions for Adrenal Insufficiency: Cellular Transplantation and Genetic Therapies
Graves, L. E., Torpy, D. J., Coates, P. T., Alexander, I. E., Bornstein, S. R., & Clarke, B. M. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac751 · Cited by 22 · see citing works
Šimůnková, K., Jovanovic, N., Rostrup, E., Methlie, P., Øksnes, M., Nilsen, R. M., Hennø, H., Tilseth, M., Godang, K., Kovac, A., et al. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0630 · Cited by 23 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease
Gan, E. H., & Pearce, S. H. S. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0581 · Cited by 18 · see citing works
Self-citationFrom Appearance of Adrenal Autoantibodies to Clinical Symptoms of Addison's Disease: Natural History
Betterle, C., Garelli, S., Presotto, F., & Furmaniak, J. (2016) · Frontiers of hormone research · doi:10.1159/000443872 · Cited by 15 · see citing works
Current and emerging therapies for Addison's disease
Napier, C., & Pearce, S. H. S. (2014) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000067 · Cited by 15 · see citing works
Self-citationHarsini, S., & Rezaei, N. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818006-8.00001-3 · Cited by 13 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Residual adrenal function in Addison’s disease
Pearce, S. H. S., Gan, E. H., & Napier, C. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0894 · Cited by 10 · see citing works
Self-citationNapier, C., Allinson, K. R., Gan, E. H., Mitchell, A. L., Gilligan, L. C., TAYLOR, A. E. R., Arlt, W., & Pearce, S. H. S. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa187 · Cited by 11 · see citing works
Self-citationB Cells and Autoantibodies in AIRE Deficiency
Wolff, A. S. B., Braun, S., Husebye, E. S., & Oftedal, B. E. (2021) · Biomedicines · doi:10.3390/biomedicines9091274 · Cited by 9 · see citing works
New era of therapy for endocrine autoimmune disorders
Oftedal, B. E., & Wolff, A. S. B. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.12961 · Cited by 7 · see citing works
Boag, A. M., Christie, M. R., McLaughlin, K. A., Syme, H. M., Graham, P. A., & Catchpole, B. (2018) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2018.05.013 · Cited by 6 · see citing works
Clinical features, investigation, and management of Addison's disease
Dong, J., Hahner, S., Bancos, I., & Tomlinson, J. (2026) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(25)00393-6 · Cited by 5 · see citing works
Isolation of a multipotent mesenchymal stem cell-like population from human adrenal cortex
Gan, E. H., Robson, W., Murphy, P., Pickard, R., Pearce, S. H. S., & Oldershaw, R. A. (2018) · Endocrine Connections · doi:10.1530/ec-18-0067 · Cited by 5 · see citing works
Self-citationAutoimmune Primary Adrenal Insufficiency: Understanding the Past, Present, and Future
Surani, A., & Carroll, T. B. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.04.008 · Cited by 4 · see citing works
Napier, C., Gan, E. H., Mitchell, A. L., Gilligan, L. C., Rees, A., Moran, C., Chatterjee, K., Vaidya, B., Arlt, W., & Pearce, S. H. S. (2018) · Endocrine Abstracts · doi:10.1530/endoabs.59.oc5.2 · Cited by 4 · see citing works
Self-citationMeasuring Human Memory B Cells in Autoimmunity Using Enzyme-Linked ImmunoSpot
Stylianou, G., Kirchenbaum, G. A., Lehmann, P., Pearce, S. H. S., & Todryk, S. M. (2025) · Biomolecules · doi:10.3390/biom15050643 · Cited by 3 · see citing works
Self-citationHeterogeneous natural history of Addison’s disease: mineralocorticoid deficiency may predominate
Howarth, S., Giovanelli, L., Napier, C., & Pearce, S. H. S. (2022) · Endocrine Connections · doi:10.1530/ec-22-0305 · Cited by 3 · see citing works
Self-citationCorticosteroid Replacement Therapy
Onyema, M. C. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.98803 · Cited by 2 · see citing works
Brooke, A. M., & Monson, J. P. (2017) · Medicine · doi:10.1016/j.mpmed.2017.05.006 · Cited by 2 · see citing works
Polyglandular Autoimmune Syndromes
Owen, C. J., Abinun, M., Pearce, S. H. S., & Cheetham, T. D. (2019) · doi:10.1002/9781119152712.ch11 · Cited by 2 · see citing works
Self-citationImmunotherapy for Fertility in Autoimmune Premature Ovarian Insufficiency
Hirschberg, A. L., Björnsdóttir, S., Gunnarsson, I., Sergouniotis, F., Wånggren, K., Silva, C. S., Vogt, E., Øksnes, M., Husebye, E. S., Bensing, S., et al. (2026) · NEJM Evidence · doi:10.1056/evidoa2500303 · Cited by 1 · see citing works
Peterson, P., & Husebye, E. S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812102-3.00039-7 · Cited by 1 · see citing works
Autoimmune Recurrence as a Cause of Adrenal Gland Graft Loss?
Buron, F., Vouillarmet, J., Thaunat, O., Thivolet, C. H., Badet, L., & Morélon, E. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13737
Betterle, C., Presotto, F., & Zanchetta, R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812102-3.00042-7
Betterle, C., Sabbadin, C., & Presotto, F. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23947-2.00056-4
Adult stem cells in regenerative medicine of endocrine system
Bailey, A. J., Bolandnazar, N. S., Najafzadeh, M., Zafar, M. S., Saeinasab, M., & Sefat, F. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-34152-6.00012-3
Autoimmune adrenalitis in adolescents in Germany: a series of 4 cases
Pudig, L., Greifoner, L., Dieke, M., Vilser, C., Hettmer, S., & Blüher, S. (2026) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2026-0187
- Authors
- Pearce, S. H. S., Mitchell, A. L., Bennett, S., King, P., Chandran, S., Nag, S., Chen, S., Smith, B. R., Isaacs, J. D., & Vaidya, B.
- Affiliations
- National Health Service (GB)
- North Tyneside General Hospital (GB)
- Bishop Auckland Hospital (GB)
- James Cook University Hospital (GB)
- R SR Ltd. (S.Che., B.R.S.), FIRS laboratories, Cardiff CF23 8HE, United Kingdom
- Royal Devon and Exeter Hospital (GB)
- Corresponding author
- Pearce, Simon H. S.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-10-01
- Volume
- 97
- Issue
- 10
- Pages
- E1927-E1932
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3462934
- OpenAlex
- W2096026597
- Cited by
- 41
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institute for Health and Care Research (ACF-2007-01-004)
- 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, rituximab, adrenal steroidogenesis, adrenal function, serum cortisol, aldosterone, immunomodulatory therapy, steroid-sparing therapy, methylprednisolone
- MeSH terms
- Rituximab, Addison Disease, Adolescent, Adrenal Cortex, Adult, Aldosterone, B-Lymphocytes, Female, Glucocorticoids, Humans, Hydrocortisone, Immunologic Factors, Lymphocyte Depletion, Male, Methylprednisolone, Middle Aged, Pilot Projects, Treatment Outcome, Antibodies, Monoclonal, Murine-Derived
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
