scholarly journals Increased risk of endocrine autoimmunity in first-degree relatives of patients with autoimmune Addison’s disease

2020 ◽  
Vol 183 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Marta Fichna ◽  
Piotr P Małecki ◽  
Mirela Młodzikowska ◽  
Bolesław Gębarski ◽  
Marek Ruchała ◽  
...  
Keyword(s):  
Family Members ◽  
Addison’S Disease ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Addison's Disease ◽  
Endocrine Disorders ◽  
Endocrine Gland ◽  
First Degree Relatives ◽  
Autoimmune Polyendocrine Syndrome ◽  
Increased Risk

Objective Autoimmune conditions tend to cluster in subjects with Addison’s disease (AD) and probably also among their relatives. The aim of the study was to estimate the frequency of the endocrine gland-specific autoantibodies in first-degree relatives of patients with AD. Methods Autoantibodies were investigated in 113 family members using RIA and ELISA assays. The control group comprised 143 age-matched volunteers. Results Autoimmune diseases were diagnosed in 38.1% relatives. Hashimoto’s thyroiditis was found in 20.3%, Graves’ disease in 8.0%, vitiligo and type 1 diabetes in 3.5%, whereas AD, rheumatoid arthritis and atrophic gastritis with pernicious anaemia in 2.7% each. All studied antibodies except for islet antigen-2 (P = 0.085) were significantly more frequent in AD relatives than in controls (P < 0.05). Antibodies to 21-hydroxylase were detected in 6.2% relatives, thyroid peroxidase in 28.3%, thyroglobulin in 19.5%, glutamic acid decarboxylase in 8.0%, and zinc transporter-8 in 7.1%. Two and more autoantibodies were detected in 18.6% subjects. Significant gender difference was revealed only for aTPO, more common in female relatives (P = 0.014; OR: 3.16; 95% CI: 1.23–8.12). Circulating autoantibodies were found more frequently in the relatives of affected males (P = 0.008; OR: 3.31; 95% CI: 1.33–8.23), and in family members of patients with polyendocrine autoimmunity (P = 0.009; OR: 3.55; 95% CI: 1.31–9.57). Conclusions This study provides evidence of increased susceptibility for the endocrine autoimmunity, especially thyroid disease, in close relatives of patients with AD. Relatives of the male AD patients and of those with autoimmune polyendocrine syndrome are at particular risk and should undergo periodic screening for autoimmune endocrine disorders.

scholarly journals Autoantibody responses in autoimmune ovarian insufficiency and in Addison's disease are IgG1 dominated and suggest a predominant, but not exclusive, Th1 type of response

2010 ◽  
Vol 163 (2) ◽  
pp. 309-317 ◽  
Author(s):  
Annalisa Brozzetti ◽  
Stefania Marzotti ◽  
Daria La Torre ◽  
Maria Luisa Bacosi ◽  
Silvia Morelli ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Control Group ◽  
Addison's Disease ◽  
Igg Subclass ◽  
Ovarian Insufficiency ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Autoimmune Polyendocrine Syndrome ◽  
Igg1 Isotype

ObjectiveSteroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17α-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity.DesignWe studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays.MethodsImmunoradiometric assays with IgG subclass-specific secondary antibodies.ResultsIn 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb.ConclusionsThe autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.

scholarly journals Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease

2008 ◽  
Vol 158 (5) ◽  
pp. 705-709 ◽  
Author(s):  
Ng'weina F. Magitta ◽  
Mikuláš Pura ◽  
Anette S Bøe Wolff ◽  
Peter Vanuga ◽  
Anthony Meager ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Monogenic Disease ◽  
Adrenal Crisis ◽  
Addison's Disease ◽  
Type I ◽  
Syndrome Type ◽  
Exon 2 ◽  
Clinical Criteria ◽  
Autoimmune Polyendocrine Syndrome ◽  
Major Mutation

BackgroundAutoimmune polyendocrine syndrome type I (APS I) is a monogenic disease affecting endocrine glands and other organs due to mutations of the autoimmune regulator (AIRE) gene. There is a wide variability in clinical phenotypes in patients with APS I, which makes the diagnosis a challenge.ObjectiveTo screen for APS I among Slovakian patients with sporadic Addison's disease and clinical features that raised the suspicion of APS I.MethodsAll 14 exons and exon–intron boundaries of the AIRE gene were sequenced. In addition, autoantibodies specific for Addison's disease and polyendocrine syndromes were assayed.ResultsUsing clinical criteria we identified four patients with APS I in three families. Two patients had a novel missense mutation in exon 2 (c.274C>T, p.R92W) and either the Finnish major mutation (c.769C>T) or the common 13 bp deletion (c.967–979del13bp). APS I was diagnosed in a brother of the latter after his death due to an adrenal crisis. A fourth patient had primary adrenal failure and hypoparathyroidism without AIRE mutations or APS-I specific autoantibodies.ConclusionsFour patients with APS I were found in a Slovakian cohort of Addison patients, although the lack of detectable AIRE mutations and APS I-specific autoantibodies raises uncertainty regarding the pathogenesis in one of the patients. This study demonstrates the merits of screening patients with phenotypic features or autoantibody findings that could indicate APS I, even in adult patients. It is necessary to identify APS I patients in order to provide appropriate treatment and follow-up of the various components of APS I.

scholarly journals Autoantibody Response Against NALP5/MATER in Primary Ovarian Insufficiency and in Autoimmune Addison's Disease

2015 ◽  
Vol 100 (5) ◽  
pp. 1941-1948 ◽  
Author(s):  
Annalisa Brozzetti ◽  
Mohammad Alimohammadi ◽  
Silvia Morelli ◽  
Viviana Minarelli ◽  
Åsa Hallgren ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Ovarian Insufficiency ◽  
Autoantibody Response ◽  
Autoimmune Polyendocrine Syndrome ◽  
Steroidogenic Cell ◽  
Healthy Control ◽  
Experimental Autoimmune

Abstract Context: NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. Objectives: The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Methods: Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects. Results: NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P &lt; .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies. Conclusions: NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.

scholarly journals Polymorphisms in the Cytotoxic T Lymphocyte Antigen-4 Gene Region Confer Susceptibility to Addison’s Disease

2004 ◽  
Vol 89 (7) ◽  
pp. 3474-3476 ◽  
Author(s):  
Anne Blomhoff ◽  
Benedicte A. Lie ◽  
Anne G. Myhre ◽  
E. Helen Kemp ◽  
Anthony P. Weetman ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Adaptive Immune System ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Endocrine Disorders ◽  
Gene Splicing ◽  
Lymphocyte Antigen ◽  
Autoimmune Thyroid ◽  
Activated T Lymphocytes

Abstract The cytotoxic T lymphocyte antigen-4 (CTLA4) gene on chromosome 2q33 encodes a key regulator in the adaptive immune system. The CTLA4 surface molecule is expressed on activated T lymphocytes and involved in down-regulation of the immune response. Previous studies on a possible association between autoimmune Addison’s disease and CTLA4 polymorphisms have shown conflicting results. A recent study identified new candidate polymorphisms in the CTLA4 region, influencing gene splicing and thereby the relative abundance of soluble CTLA4. We genotyped 134 patients with Addison’s disease and 413 healthy controls from Norway and United Kingdom for these newly identified polymorphisms. Our data demonstrate that the same polymorphisms that have recently been demonstrated to confer susceptibility to autoimmune thyroid disease and type 1 diabetes also confer susceptibility to Addison’s disease. This finding suggests that polymorphisms in CTLA4 confer general risk to develop autoimmunity and identifies a potential therapeutic target in the prevention of autoimmune endocrine disorders.

SUBCLINICAL HYPOTHYROIDISM IN ADDISON'S DISEASE

1979 ◽  
Vol 91 (4) ◽  
pp. 674-679 ◽  
Author(s):  
Jens Faber ◽  
Dorte Cohn ◽  
Carsten Kirkegaard ◽  
Morten Christy ◽  
Kaj Siersbæk-Nielsen ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Mean Value ◽  
Normal Serum ◽  
Control Group ◽  
Addison's Disease ◽  
Normal Range ◽  
Microsomal Antibody ◽  
The Mean ◽  
Thyroid Microsomal Antibodies ◽  
Serum Tsh

ABSTRACT Fourteen patients with Idiopatic Addison's disease (IAD) were studied in order to detect a possible subclinical hypothyroid state. All were clinically euthyroid with normal serum thyroxine (T4) and serum 3,5′,3′-triiodothyronine (T3). Eleven had circulating thyroid microsomal antibodies in blood. The mean basal serum TSH was significantly higher than that of the control group but only three patients had values above the upper normal range. The mean value of serum T4 was decreased as compared to that of the normal persons, while serum 3,3′,5′-triiodothyronine was elevated. 7.5 mU bovine thyrotrophin per kilogram body weight injected intravenously caused a rise in serum T3 not different from the response in normals. However, as well increasing serum TSH as increasing microsomal antibody titer correlated significantly to decreasing thyroidal release of T3. Our results suggest that clinically euthyroid patients suffering from IAD might have a beginning thyroidal insufficiency because of a progressive immunological damage of the thyroid.

scholarly journals Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mahdi Mahdavi ◽  
Atieh Amouzegar ◽  
Ladan Mehran ◽  
Elham Madreseh ◽  
Maryam Tohidi ◽  
...  
Keyword(s):  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Normal Weight ◽  
Control Group ◽  
Overt Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Cross Sectional ◽  
Increased Risk ◽  
Prevalence Of Obesity ◽  
Thyroid Dysfunctions

Abstract Background Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals. Method This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group. Results We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism’s overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15–3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04–1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results. Conclusions Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.

scholarly journals Familial Association between Coeliac Disease and Ulcerative Colitis: Preliminary Communication

1986 ◽  
Vol 79 (4) ◽  
pp. 204-205 ◽  
Author(s):  
J F Mayberry ◽  
H L Smart ◽  
P J Toghill
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Coeliac Disease ◽  
Family Members ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Familial Association ◽  
Preliminary Communication

One hundred and twenty patients who were members of the Nottinghamshire Coeliac Group completed a questionnaire about the occurrence of coeliac disease, ulcerative colitis and Crohn's disease amongst first-degree relatives. Siblings were at a 20-fold risk of developing coeliac disease and a 15-fold risk of developing ulcerative colitis, and significantly increased risks for these two conditions were also seen in other family members. The relatives of patients with coeliac disease are at increased risk not only of developing coeliac disease but also ulcerative colitis. This provides further support for a possible role of a dietary allergen in the development of ulcerative colitis.

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.

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