Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency.
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.
To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ- or non-organ-specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison's disease (AD) or chronic candidiasis (CC).
Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome.
Recently, associations of several single-nucleotide polymorphisms (SNPs) within the CLEC16A gene with multiple sclerosis (MS), type-I diabetes, and primary adrenal insufficiency were reported.
In addition, other genes also implicated in other autoimmune diseases are linked to Addison's disease, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), major histocompatibility complex class II transactivator (CIITA), and most recently the C-lectin type gene (CLEC16A).
Two alleles at 16p13 are independently associated with the risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
Two alleles at 16p13 are independently associated with the risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
Two alleles at 16p13 are independently associated with the risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
Two alleles at 16p13 are independently associated with the risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disease caused by loss of function of the peroxisomal transporter ABCD1 (ALD), which results in accumulation of very long chain fatty acids (VLCFAs) in organs and serum, central demyelination and peripheral axonopathy and Addison's disease.
We discuss (a) the role of the nuclear receptors DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human adrenal and reproductive dysfunction; (b) multisystem growth restriction syndromes due to gain-of-function in the growth repressors CDKN1C (IMAGE syndrome) and SAMD9 (MIRAGE syndrome), or loss of POLE1; (c) nonclassic forms of STAR and P450scc/CYP11A1 insufficiency that present with a delayed-onset adrenal phenotype and represent a surprisingly prevalent cause of undiagnosed PAI; and (d) a new sphingolipidosis causing PAI due to defects in sphingosine-1-phosphate lyase-1 (SGPL1).
Subsequent endocrine assessment with a synthetic adrenocorticotropin hormone (ACTH) stimulation test and measurement of ACTH levels revealed primary adrenal insufficiency also known as Morbus Addison.
After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x<sup>2</sup>p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x<sup>2</sup>p = 0.02, OR 8.43).
In both groups, none of the patients who had sufficient preoperative ACTH without hydrocortisone supplementation (n=15) showed hypocortisolism in the immediate postoperative measurement.
Moreover, six of 10 patients had a blunted cortisol response after ACTH stimulation, thus confirming the diagnosis of primary adrenal insufficiency (PAI).
The Montecarlo Exact Fisher Test demonstrated marked differences in all three Loci, DQA1, DQB1, DRB1 (p<0.0001) between AP versus both AITD and controls, as well as between AP type II (Addison's disease as major endocrine component) and AP type III (T1D + AITD).
After applying a stepwise logistic regression model, only the group of diagnoses, including salt wasting CAH, AHC, and Addison's disease, remained significant predictor of AC (OR 17.5, 95% CI 4.7-64.9, P < 0.001).