Residual adrenal function in autoimmune addison's disease - effect of dual therapy with rituximab and depot tetracosactide
| Autor: | R. Andrew James, Lorna C Gilligan, Bijay Vaidya, Anna L. Mitchell, Catherine Napier, Krishna Chatterjee, Earn H Gan, Simon H. S. Pearce, D. Aled Rees, Simon Ashwell, Carla Moran, Wiebke Arlt, Yaasir Mamoojee |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine steroidogenesis Hydrocortisone Endocrinology Diabetes and Metabolism Clinical Biochemistry Biochemistry Basal (phylogenetics) 0302 clinical medicine Endocrinology Addison Disease Adrenal Glands Clinical Research Article Middle Aged 3. Good health residual adrenal function Addison's disease Drug Therapy Combination Female Rituximab immunotherapy AcademicSubjects/MED00250 Glucocorticoid medicine.drug Adult medicine.medical_specialty Addison’s disease regenerative medicine 030209 endocrinology & metabolism Context (language use) adrenocorticotropin Young Adult 03 medical and health sciences Adrenocorticotropic Hormone Internal medicine Multicenter trial medicine Humans Immunologic Factors Endocrine system business.industry Biochemistry (medical) medicine.disease Hormones 030104 developmental biology Clinical research Quality of Life Cosyntropin business Biomarkers Follow-Up Studies |
| Zdroj: | The Journal of Clinical Endocrinology and Metabolism |
| ISSN: | 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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