Residual adrenal function in autoimmune Addison's disease-effect of dual therapy with rituximab and depot tetracosactide
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Context
In autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy, and poorer quality of life.
Objective
The objective of this article is to restore adrenocortical steroidogenic function in recent-onset AAD.
Design
An open-label, multicenter trial of immunotherapy and trophic stimulation in new-onset AAD was conducted. Serial measurement of serum and urine corticosteroids at baseline and throughout a 72-week follow-up period was performed.
Setting
This study was conducted at the
endocrine departments and clinical research facilities at 5 UK tertiary centers.
Patients
Thirteen participants (9 female, 4 male; age 19-64 years) were included with AAD confirmed by high adrenocorticotropin, low circulating cortisol (basal < 100 nmol/L or post-tetracosactide < 300 nmol/L), and positive serum 21-hydroxylase antibodies.
Intervention
All participants received dual therapy with B-lymphocyte–depleting immunotherapy (rituximab 1 g given twice) and repeated depot tetracosactide (1 mg on alternate days for 12 weeks).
Main Outcome Measure
Restoration of normal GC secretion (stimulated cortisol > 550 nmol/L) at week 48 was the main outcome measure.
Results
Ten of 13 (77%) participants had detectable stimulated serum cortisol (26-265 nmol/L) at trial entry. Following intervention, 7 of 13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325 nmol/L at week 18 in 1 participant. Increased steroid metabolites, assayed by urine gas chromatography–mass spectrometry at week 12 and week 48, was detected in 8 of 13 (62%) individuals, reflecting an increase in endogenous steroidogenesis. Four of 13 had residual adrenal function at 72 weeks.
Conclusion
Combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients, and this has the potential to be exploited to improve adrenal function.
In autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy, and poorer quality of life.
Objective
The objective of this article is to restore adrenocortical steroidogenic function in recent-onset AAD.
Design
An open-label, multicenter trial of immunotherapy and trophic stimulation in new-onset AAD was conducted. Serial measurement of serum and urine corticosteroids at baseline and throughout a 72-week follow-up period was performed.
Setting
This study was conducted at the
endocrine departments and clinical research facilities at 5 UK tertiary centers.
Patients
Thirteen participants (9 female, 4 male; age 19-64 years) were included with AAD confirmed by high adrenocorticotropin, low circulating cortisol (basal < 100 nmol/L or post-tetracosactide < 300 nmol/L), and positive serum 21-hydroxylase antibodies.
Intervention
All participants received dual therapy with B-lymphocyte–depleting immunotherapy (rituximab 1 g given twice) and repeated depot tetracosactide (1 mg on alternate days for 12 weeks).
Main Outcome Measure
Restoration of normal GC secretion (stimulated cortisol > 550 nmol/L) at week 48 was the main outcome measure.
Results
Ten of 13 (77%) participants had detectable stimulated serum cortisol (26-265 nmol/L) at trial entry. Following intervention, 7 of 13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325 nmol/L at week 18 in 1 participant. Increased steroid metabolites, assayed by urine gas chromatography–mass spectrometry at week 12 and week 48, was detected in 8 of 13 (62%) individuals, reflecting an increase in endogenous steroidogenesis. Four of 13 had residual adrenal function at 72 weeks.
Conclusion
Combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients, and this has the potential to be exploited to improve adrenal function.
Date Issued
2020-04-01
Date Acceptance
2019-12-19
Citation
Journal of Clinical Endocrinology and Metabolism (JCEM), 2020, 105 (4), pp.e1250-e1259
ISSN
0021-972X
Publisher
Oxford University Press
Start Page
e1250
End Page
e1259
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism (JCEM)
Volume
105
Issue
4
Copyright Statement
© Endocrine Society 2019. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits un restricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31863094
PII: 5682802
Subjects
21-HYDROXYLASE
Addison's disease
adrenocorticotropin
B-LYMPHOCYTE DEPLETION
BONE-MINERAL DENSITY
CORTISOL
CRISIS
Endocrinology & Metabolism
immunotherapy
INSUFFICIENCY
Life Sciences & Biomedicine
MORTALITY
regenerative medicine
residual adrenal function
RISK
Science & Technology
steroidogenesis
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-12-21