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):  
C. Betterle
Keyword(s):  
Autoimmune Diseases ◽  
Adrenal Cortex ◽  
Addison’S Disease ◽  
Adult Patients ◽  
Addison's Disease ◽  
Organ Specific

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 II. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Children with Organ-Specific Autoimmune Diseases: Markers of High Progression to Clinical Addison’s Disease

1997 ◽  
Vol 82 (3) ◽  
pp. 939-942
Author(s):  
Corrado Betterle ◽  
Marina Volpato ◽  
Bernard Rees Smith ◽  
Jadwiga Furmaniak ◽  
Shu Chen ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Adrenal Cortex ◽  
Addison’S Disease ◽  
Adrenal Function ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Organ Specific ◽  
Cleavage Enzyme

Abstract Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA were found in 14 children (1.7%), mostly in hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative children were followed up for a maximum of 10 yr by evaluation of adrenocortical function (ACTH test) and autoantibody status. In all patients steroid-producing cell autoantibodies were assessed by immunofluorescence and autoantibodies to steroid 21-hydroxylase, 17α-hydroxylase, and cytochrome P450 side-chain cleavage enzyme by immunoprecipitation assay. All 10 ACA-positive patients were positive for 21-hydroxylase autoantibodies. Six were positive for steroid-producing cell autoantibodies and 5 also for autoantibodies to 17α-hydroxylase and/or P450 side-chain cleavage enzyme. Overt Addison’s disease developed in 9 (90%) ACA/21-OH-antibody-positive children after 3–121 months, and 1 remaining child had subclinical hypoadrenalism. By contrast, all ACA/21-OH antibody-negative children maintained normal adrenal function. Adrenal failure was not related to ACA titres, sex, adrenal function, type of preexisting autoimmune disorder, or human leucocyte antigens D-related status. In conclusion, in children with autoimmune endocrine diseases, ACA/21-hydroxylase autoantibodies are important predictive markers for the development of Addison’s disease.

scholarly journals Addison's disease: a survey on 633 patients in Padova

2013 ◽  
Vol 169 (6) ◽  
pp. 773-784 ◽  
Author(s):  
Corrado Betterle ◽  
Riccardo Scarpa ◽  
Silvia Garelli ◽  
Luca Morlin ◽  
Francesca Lazzarotto ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Adrenal Cortex ◽  
Gene Mutations ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Genetic Profile ◽  
Recent Onset ◽  
Autoimmune Polyendocrine Syndrome ◽  
Adrenal Imaging ◽  
Genetic Features

ObjectiveAddison's disease (AD) is a rare endocrine condition.DesignWe aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed up since 1967.MethodsAdrenal cortex autoantibodies, presence of other autoimmune and nonautoimmune diseases, nonadrenal autoantibodies, adrenal imaging, and genetic profile for HLA-DRB1 and AIRE were analyzed.ResultsA total of 492 (77.7%) patients were found to be affected by autoimmune AD (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic-associated AD, 10 (1.6%) adrenal cancer, six (0.94%) post-surgical AD, four (0.6%) vascular disorder-related AD, three (0.5%) post-infectious AD, and 32 (5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the vast majority (88–100%) of patients with recent onset A-AD, but in none of those with nonautoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A-AD patients: 88% of patients with A-AD had other clinical or subclinical autoimmune diseases or were positive for nonadrenal autoantibodies.Based on the coexistence of other autoimmune disorders, 65.6% of patients with A-AD were found to have type 2 autoimmune polyendocrine syndrome (APS2), 14.4% have APS1, and 8.5% have APS4. Class II HLA alleles DRB1*03 and DRB1*04 were increased, and DRB1*01, DRB1*07, DRB1*013 were reduced in APS2 patients when compared with controls. Of the patients with APS1, 96% were revealed to have AIRE gene mutations.ConclusionsA-AD is the most prevalent form of adrenal insufficiency in Italy, and ∼90% of the patients are adrenal autoantibody-positive at the onset. Assessment of patients with A-AD for the presence of other autoimmune diseases should be helpful in monitoring and diagnosing APS types 1, 2, or 4 and improving patients' care.

scholarly journals 21-hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison's disease

1997 ◽  
Vol 107 (2) ◽  
pp. 341-346 ◽  
Author(s):  
A. FALORNI ◽  
S. LAURETI ◽  
A. NIKOSHKOV ◽  
M. L. PICCHIO ◽  
B. HALLENGREN ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Addison’S Disease ◽  
Adult Patients ◽  
Addison's Disease

scholarly journals Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study

2020 ◽  
Vol 182 (5) ◽  
pp. 473-480 ◽  
Author(s):  
Jakob Skov ◽  
Daniel Eriksson ◽  
Ralf Kuja-Halkola ◽  
Jonas Höijer ◽  
Soffia Gudbjörnsdottir ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Atrophic Gastritis ◽  
Genetic Factors ◽  
Monozygotic Twins ◽  
Twin Studies ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Graves Disease ◽  
Dizygotic Twins ◽  
Organ Specific

Objective Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environmental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organ-specific autoimmune diseases. Design Prospective twin cohort study. Methods We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto’s thyroiditis, atrophic gastritis, celiac disease, Graves’ disease, type 1 diabetes, vitiligo and Addison’s disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data. Results Co-aggregation was more pronounced in monozygotic twins (median HR: 3.2, range: 2.2–9.2) than in dizygotic twins (median HR: 2.4, range: 1.1–10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23–0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49–0.71) for Graves’ disease to 0.97 (95% CI: 0.91–1.00) for Addison’s disease. Conclusions Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.

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.

scholarly journals Etiological and clinical structure of primary chronic adrenal insufficiency: retrospective analysis of 426 cases

1998 ◽  
Vol 44 (6) ◽  
pp. 22-26
Author(s):  
V. V. Fadeev ◽  
I. I. Buziashvili ◽  
I. I. Dedov
Keyword(s):  
Family History ◽  
Autoimmune Diseases ◽  
Adrenal Insufficiency ◽  
Retrospective Analysis ◽  
Dynamic Assessment ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Medical Academy ◽  
History Of ◽  
Close Relatives

A retrospective analysis of case histories of 426 patients with primary chronic adrenal insufficiency (1-AI), followed up at Endocrinology Research Center, Russian Academy of Medical Sciences, and/or Endocrinology Clinic of I. M. Setchenov Moscow Medical Academy in 1954-1977, was carried out in order to assess the etiological and clinical structure of this disease. The idiopathic form of Addison 's disease prevailed over its tuberculous form (70 and 30%), respectively); dynamic assessment of morbidity over the above period showed a progressive predominance of the idiopathic form. 1-AI is more than 2 times more incident in women, and the incidence of the disease in women vs. men is ever growing. There are at least 2.5 times more women than men among patients with idiopathic Addison's disease, while for the tuberculous form the ratio is 1:1. The mean age of 1-AI manifestation is 34.3 ± 0.46 years. The peak of clinical manifestation of idiopathic Addison's disease occurs between 20 and 40 years (at the age of 32.8 years on average), while for the tuberculous form this age is 30-50 years (37.4), which indicates a later manifestation of this form (p < 0.01). In 28%) cases idiopathic Addison's disease coursed in the presence of autoimmune polyglandular syndromes (APS): type 1 in 3%o and type II in 25% cases. Dynamic assessment of the ratio of the incidence of 1-AI alone to that in the presence of APS showed that from the thirties to the fifties, idiopathic Addison's disease was a component of APS in 13 % cases and by the eighties and nineties this values increased to 34%), which permits a conclusion about pathomorphism of 1-AI, consisting in gradual transfer of this disease into APS. Many patients with 1-AI develop concomitant autoimmune diseases; analysis of family history of such patients reveals autoimmune diseases in close relatives in many cases, while the majority of patients with the tuberculous form of Addison 5 disease have a family history of tuberculosis.

The natural history of autoimmune Addison’s disease with a non-classical presentation: a case report and review of literature

2018 ◽  
Vol 56 (6) ◽  
pp. 896-900 ◽  
Author(s):  
Jacopo Manso ◽  
Raffaele Pezzani ◽  
Riccardo Scarpa ◽  
Nicoletta Gallo ◽  
Corrado Betterle
Keyword(s):  
Natural History ◽  
Adrenal Cortex ◽  
Clinical Manifestations ◽  
Addison’S Disease ◽  
Plasma Renin ◽  
Dehydroepiandrosterone Sulfate ◽  
Addison's Disease ◽  
Acth Stimulation ◽  
Basal Cortisol ◽  
History Of

Abstract Autoimmune Addison’s disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto’s thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.

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