Partial recovery of adrenal function in a patient with autoimmune Addison’s disease

2008 ◽  
Vol 31 (7) ◽  
pp. 672-674 ◽  
Author(s):  
L. C. C. J. Smans ◽  
P. M. J. Zelissen
Keyword(s):  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease ◽  
Partial Recovery

scholarly journals Residual Adrenal Function in Autoimmune Addison’s Disease—Effect of Dual Therapy With Rituximab and Depot Tetracosactide

2019 ◽  
Vol 105 (4) ◽  
pp. e1250-e1259 ◽  
Author(s):  
Catherine Napier ◽  
Earn H Gan ◽  
Anna L Mitchell ◽  
Lorna C Gilligan ◽  
D Aled Rees ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Outcome Measure ◽  
Combined Treatment ◽  
Addison’S Disease ◽  
Dual Therapy ◽  
Adrenal Function ◽  
Gas Chromatography Mass Spectrometry ◽  
Addison's Disease ◽  
Open Label ◽  
Main Outcome Measure

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.

scholarly journals Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1–24) Treatment

2014 ◽  
Vol 99 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Earn H. Gan ◽  
Katie MacArthur ◽  
Anna L. Mitchell ◽  
Beverly A. Hughes ◽  
Petros Perros ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease

scholarly journals Estimated Risk for Developing Autoimmune Addison’s Disease in Patients with Adrenal Cortex Autoantibodies

2006 ◽  
Vol 91 (5) ◽  
pp. 1637-1645 ◽  
Author(s):  
Graziella Coco ◽  
Chiara Dal Pra ◽  
Fabio Presotto ◽  
Maria Paola Albergoni ◽  
Cristina Canova ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Cox Model ◽  
Cumulative Risk ◽  
Human Leukocyte ◽  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease ◽  
Risk Algorithm ◽  
Functional Factors ◽  
Estimated Risk

Context: Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison’s disease (AAD) are at risk of adrenal failure. Design: To assess the contribution of different clinical, immunological, genetic, and functional factors in the progression to AAD, we followed up 100 ACA-positive and 63 ACA-negative patients without AAD for a maximum of 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence and 21-OH autoantibodies (Abs) by RIA. Adrenal function was assessed by measuring basal levels of cortisol, aldosterone, ACTH, renin activity, and cortisol response to ACTH. The risk of developing AAD was calculated using survival and multivariate analyses. Results: AAD developed in 31 ACA-positive patients and one ACA-negative patient. The cumulative risk of disease in ACA-positive patients was 48.5% [95% confidence interval (CI) 40.8–56.1]. The cumulative risk was higher in children than adults (100 vs. 31.9%; P < 0.0001), males than females (68.6 vs. 42.7%; P = 0.006), patients with subclinical rather than normal adrenal function at entry (87.4 vs. 30.1%; P < 0.0001), patients with hypoparathyroidism and/or candidiasis than patients with other autoimmune or nonautoimmune diseases (100 vs. 29.7%; P < 0.0001), and patients with high rather than low-medium ACA titers (62.8 vs. 41.2%; P = 0.12). The presence of human leukocyte antigen (HLA)-DRB1 did not appear to contribute to the prediction of AAD. Adjusted hazard ratios by Cox model for the development of AAD were 3.37 for males (CI 1.38–8.24), 5.23 for hypoparathyroidism and/or candidiasis (CI 1.53–17.92), 3.33 for high antibody titers (CI 1.43–7.78), and 6.15 for impaired adrenal function at entry (CI 2.79–13.57). Conclusions: These results were used to construct a risk algorithm for estimating the probability of developing AAD from the combination of gender, age, adrenal function, antibody titer, and associated autoimmune disorders at entry. The values of estimated risk could be used to decide appropriate follow-up intervals and future immunointervention strategies.

The natural history of adrenal function in autoimmune patients with adrenal autoantibodies

1988 ◽  
Vol 117 (3) ◽  
pp. 467-475 ◽  
Author(s):  
C. Betterle ◽  
C. Scalici ◽  
F. Presotto ◽  
B. Pedini ◽  
L. Moro ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Plasma Renin ◽  
Autoimmune Disorder ◽  
Adrenal Function ◽  
Adrenocortical Function ◽  
Diabetic Patients ◽  
Addison's Disease ◽  
Gonadal Dysfunction ◽  
Insulin Dependent Diabetic ◽  
Low Cortisol

ABSTRACT Adrenal autoantibodies (AA) were found in 23 of 2571 (0·9%) patients with organ-specific autoimmune diseases, in one of 632 first-degree relatives of insulin-dependent diabetic patients, and in none of 375 normal controls. In AA-positive subjects the prevalence of human leucocyte antigens (HLA)-A1, -B8 and -DR3 was significantly higher with respect to the general population. Two groups were followed (15 subjects persistently positive for AA and 51 negative subjects) for a mean period of 3·2 years. Yearly tests were made for AA and adrenal function. Of the 15 subjects persistently positive for AA, six developed Addison's disease after a period varying from 6 months to 10 years. Of the 51 subjects initially negative, two became positive during follow-up, and one of these developed Addison's disease 16 months later. In contrast, all the remaining 49 persistently negative subjects maintained normal adrenal function tests. Overall, of the 17 positive subjects, seven (41%) developed Addison's disease, three (18%) showed various degrees of subclinical adrenocortical failure and the remaining seven maintained normal glandular function. In the positive patients the yearly incidence of detriment in adrenal function was 19%. Patients who developed Addison's disease showed significant association with HLA-B8 phenotype. The development from normal adrenocortical function to overt Addison's disease seemed to progress through four distinct stages of functional impairment: increased plasma renin activity with normal/low aldosterone (stage 1), low cortisol response after i.v. administration of ACTH (stage 2), increased ACTH (stage 3), and low basal cortisol (stage 4). Thus, idiopathic Addison's disease appears to be a chronic autoimmune disorder with a genetic predisposition and a long preclinical period marked by the presence of AA. Steroid-producing cell antibodies were also evaluated but they were not found to be markers of gonadal dysfunction. J. Endocr. (1988) 117, 467–475

scholarly journals I. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Adult Patients with Organ-Specific Autoimmune Diseases: Markers of Low Progression to Clinical Addison’s Disease

1997 ◽  
Vol 82 (3) ◽  
pp. 932-938 ◽  
Author(s):  
Corrado Betterle ◽  
Marina Volpato ◽  
Bernard Rees Smith ◽  
Jadwiga Furmaniak ◽  
Shu Chen ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Prospective Study ◽  
Adrenal Cortex ◽  
Addison’S Disease ◽  
Adrenal Function ◽  
Adult Patients ◽  
Addison's Disease ◽  
Chain Cleavage ◽  
Organ Specific ◽  
A Prospective Study

Abstract Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylase (21-OH), steroid 17α-hydroxylase (17α-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17α-OH and/or P450scc. During the prospective study, overt Addison’s disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison’s disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17α-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison’s disease. .

scholarly journals Recovery of adrenal function in a patient with confirmed Addison's disease

2013 ◽  
Vol 2013 ◽  
Author(s):  
M Baxter ◽  
S Gorick ◽  
F M Swords
Keyword(s):  
Replacement Therapy ◽  
Adrenal Glands ◽  
Addison’S Disease ◽  
Serum Cortisol ◽  
Addison's Disease ◽  
List Type ◽  
Partial Recovery ◽  
Post Dose ◽  
Adrenal Axis ◽  
Immune Mediated

Summary Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Learning points Partial recovery from Addison's disease is possible although uncommon. Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management. As further reports of adrenal axis recovery emerge, this may influence the counselling given to patients with Addison's disease in the future.

Revival of adrenal function in established autoimmune Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Earn H Gan ◽  
Anna L Mitchell ◽  
Petros Perros ◽  
Andy James ◽  
Steve Ball ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease

scholarly journals THE BLOOD PICTURE IN ADDISON’S DISEASE

Blood ◽  
1948 ◽  
Vol 3 (7) ◽  
pp. 769-773 ◽  
Author(s):  
JOSÉ BÁEZ-VILLASEÑOR ◽  
CHARLES E. RATH ◽  
CLEMENT A. FINCH
Keyword(s):  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease ◽  
Blood Picture ◽  
Impaired Ability

Abstract The blood picture of 100 patients with Addison’s disease was analyzed. Under basal conditions, there was a tendency toward lymphocytosis and neutropenia. Under stress, the blood picture remained fixed. The impaired ability of those patients to show leucocytosis and lymphopenia is attributable to their impaired adrenal function. While large doses of desoxycorticosterone and maintenance doses of adrenal extract had no effect on the blood picture, 17-oxysteroids produce both neutrophilia and lymphopenia. The anemia present in Addison’s disease is normocytic and normochromic.

Sign in / Sign up

Export Citation Format

Share Document