Document Detail


Adrenal steroidogenesis after B lymphocyte depletion therapy in new-onset Addison's disease.
MedLine Citation:
PMID:  22767640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Simon H S Pearce; Anna L Mitchell; Stuart Bennett; Phil King; Sukesh Chandran; Sath Nag; Shu Chen; Bernard Rees Smith; John D Isaacs; Bijay Vaidya
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-05
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  97     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2012-12-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1927-32     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00753597
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MeSH Terms
Descriptor/Qualifier:
Addison Disease / drug therapy*,  immunology*
Adolescent
Adrenal Cortex / immunology
Adult
Aldosterone / blood*
Antibodies, Monoclonal, Murine-Derived / administration & dosage
B-Lymphocytes / immunology*
Female
Glucocorticoids / administration & dosage
Humans
Hydrocortisone / blood*
Immunologic Factors / administration & dosage
Lymphocyte Depletion / methods*
Male
Methylprednisolone / administration & dosage
Middle Aged
Pilot Projects
Treatment Outcome
Grant Support
ID/Acronym/Agency:
G0701632//Medical Research Council; G07017632//Medical Research Council; G0900390//Medical Research Council
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal, Murine-Derived; 0/Glucocorticoids; 0/Immunologic Factors; 0/rituximab; 4964P6T9RB/Aldosterone; WI4X0X7BPJ/Hydrocortisone; X4W7ZR7023/Methylprednisolone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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