scholarly journals MANAGEMENT OF ENDOCRINE DISEASE Disease burden and treatment challenges in patients with both Addison’s disease and type 1 diabetes mellitus

2020 ◽  
Vol 183 (1) ◽  
pp. R1-R11
Author(s):  
Dimitrios Chantzichristos ◽  
Björn Eliasson ◽  
Gudmundur Johannsson
Keyword(s):  
Type 1 Diabetes ◽  
Management Strategies ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Addison’S Disease ◽  
Adrenal Crisis ◽  
Addison's Disease ◽  
Autoimmune Thyroid ◽  
Increased Risk

Concurrent type 1 diabetes (T1D) and Addison’s disease (AD) is a rare combination of diseases and, in approximately one third of these patients, it is also combined with an autoimmune thyroid disease. Recently, it was shown that patients with both T1D and AD have a higher risk of premature death compared to patients with T1D alone, the most common causes of death being due to diabetic complications and cardiovascular disease. These patients receiving replacement therapies with both insulin and glucocorticoids face an increased risk of hypo- and hyperglycemia and diabetic ketoacidosis and have a higher risk of adrenal crisis than patients with AD alone. Treatment challenges include the opposing effects of insulin and glucocorticoids on glucose homeostasis and the need to balance and synchronize these two treatments. The rarity of this disease combination may explain the paucity of data on outcome and specific treatment strategies in this patient group. Based on this review, we suggest management strategies for their insulin and glucocorticoid replacement therapies and indicate future areas of research.

A new ELISA for autoantibodies to steroid 21-hydroxylase

2018 ◽  
Vol 56 (6) ◽  
pp. 933-938 ◽  
Author(s):  
Maria del Pilar Larosa ◽  
Shu Chen ◽  
Nora Steinmaus ◽  
Hannah Macrae ◽  
Liang Guo ◽  
...  
Keyword(s):  
Blood Donors ◽  
Addison’S Disease ◽  
Test Sample ◽  
Adult Patients ◽  
Addison's Disease ◽  
Systemic Lupus Erythematosis ◽  
Autoimmune Thyroid ◽  
Increased Risk ◽  
Streptavidin Peroxidase

Abstract Background: A new ELISA for autoantibodies to steroid 21-hydroxylase (21-OH Ab) is described. Methods: In the assay test sample autoantibodies form a bridge between 21-OH coated onto the plate well and liquid phase 21-OH-biotin. Bound 21-OH-biotin is detected by the addition of streptavidin peroxidase and colorogenic peroxidase substrate. Results: Of 100 samples from patients with autoimmune Addison’s disease, 86 (86%) were positive for 21-OH Ab ELISA whereas 84 (84%) were positive in an immunoprecipitation assay based on 125I-labeled 21-OH. Six (0.6%) of 928 healthy adult blood donors and 1 (2.0%) of 49 adult patients with type 1 diabetes mellitus (T1DM) were positive by ELISA. No samples from adult patients with Graves’ disease (GD; n=50), celiac disease (n=29), systemic lupus erythematosis (n=9) or rheumatoid arthritis (n=20) were positive by ELISA. However, 2/51 (3.9%) children with GD, 3/69 (4.3%) children with Hashimoto’s thyroiditis (HT) and 3/119 (2.5%) children with T1DM alone or associated with autoimmune thyroid disorders were ELISA positive. Conclusions: The new assay should be useful for screening patients known to be at increased risk of developing clinical autoimmune Addison’s disease, in particular children with HT, GD and/or T1DM.

scholarly journals HLA Class II Haplotypes Differentiate Between the Adult Autoimmune Polyglandular Syndrome Types II and III

2014 ◽  
Vol 99 (1) ◽  
pp. E177-E182 ◽  
Author(s):  
B. K. Flesch ◽  
N. Matheis ◽  
T. Alt ◽  
C. Weinstock ◽  
J. Bux ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Addison’S Disease ◽  
Class Ii ◽  
Hla Class Ii ◽  
Addison's Disease ◽  
Type Ii ◽  
Autoimmune Thyroid ◽  
Autoimmune Polyglandular Syndrome ◽  
Hla Class Ii Alleles

Background: Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood. Aim: The aim of this study was to gain further insight into the genetics of the adult APS types. Site: The study was conducted at a university referral center. Methods: The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level. Results: Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P < .001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc < .001) and controls (Pc < .01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were overrepresented in APS (Pc < .001). Combination of both haplotypes to a genotype was highly prevalent in APS vs AITD and controls (Pc < .001). Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc < .001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc < .001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II (Pc < .01). Conclusions: HLA class II haplotypes differentiate between the adult APS types II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.

scholarly journals Type 1 Diabetes and Addison’s Disease: When the Diagnosis Is Suggested by the Continuous Glucose Monitoring System

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 702
Author(s):  
Francesco Vinci ◽  
Giuseppe d’Annunzio ◽  
Flavia Napoli ◽  
Marta Bassi ◽  
Carolina Montobbio ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Adrenal Insufficiency ◽  
Continuous Glucose Monitoring ◽  
Young Patients ◽  
Glucose Monitoring ◽  
Addison’S Disease ◽  
Insulin Dosage ◽  
Adrenal Crisis ◽  
Addison's Disease

Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison’s disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison’s disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison’s disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data.

Retrovirus-Like Long-Terminal Repeat DQ-LTR13 and Genetic Susceptibility to Type 1 Diabetes and Autoimmune Addison's Disease

Diabetes ◽  
2005 ◽  
Vol 54 (3) ◽  
pp. 900-905 ◽  
Author(s):  
G. Gambelunghe ◽  
I. Kockum ◽  
V. Bini ◽  
G. D. Giorgi ◽  
F. Celi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Long Terminal Repeat ◽  
Genetic Susceptibility ◽  
Addison’S Disease ◽  
Terminal Repeat ◽  
Addison's Disease

scholarly journals Familial associations for Addison’s disease and between Addison’s disease and other autoimmune diseases

2020 ◽  
Vol 9 (11) ◽  
pp. 1114-1120
Author(s):  
Hauke Thomsen ◽  
Xinjun Li ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Asta Försti ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Familial Risk ◽  
Addison’S Disease ◽  
Population Based ◽  
Addison's Disease ◽  
Genetic Etiology ◽  
Polygenic Inheritance ◽  
Relative Risks ◽  
Very High

Design Addison’s disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, present as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce, and we aimed to carry out an unbiased study on AD and related AIDs. Methods We collected data on patients diagnosed with AIDs in Swedish hospitals and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks. Results The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was associated with 11 other AIDs, including thyroid AIDs and type 1 diabetes and some rarer AIDs such as Guillain–Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren’s syndrome. Conclusions The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.

scholarly journals Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto’s thyroiditis or Addison’s disease in the German population

2005 ◽  
Vol 153 (6) ◽  
pp. 895-899 ◽  
Author(s):  
Heinrich Kahles ◽  
Elizabeth Ramos-Lopez ◽  
Britta Lange ◽  
Oliver Zwermann ◽  
Martin Reincke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Hashimoto’S Thyroiditis ◽  
Addison’S Disease ◽  
Hashimoto's Thyroiditis ◽  
Addison's Disease ◽  
Healthy Controls ◽  
Significant Difference

Background: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor. Materials and Methods: Patients with type 1 diabetes (n = 220), Hashimoto’s thyroiditis (n = 94), Addison’s disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T. Results: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3–2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto’s thyroiditis or Addison’s disease and healthy controls. Conclusion: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females.

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