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BMJ Case Reports Jul 2013Addison's disease is a relatively rare endocrine condition resulting from adrenal insufficiency due to various causes. Weight loss is a common feature; however, patients...
Addison's disease is a relatively rare endocrine condition resulting from adrenal insufficiency due to various causes. Weight loss is a common feature; however, patients may be seen by a variety of specialists, even requiring acute admission before the diagnosis is made. Addison's disease is commonly associated with other autoimmune diseases. In some cases such as autoimmune polyendocrine syndromes (APS) types 1 and 2, these associations are more commonly found. We present a case of one such patient who presented to the acute medical team having been referred to the gastrointestinal services in the previous year for persistent vomiting and weight loss. On review of history, the cause of vomiting and weight loss was questioned and combined with subsequent biochemical testing a diagnosis of Addison's disease was made. The patient was also noted to have other associated endocrine and autoimmune conditions.
Topics: Addison Disease; Diagnosis, Differential; Female; Humans; Hydrocortisone; Treatment Outcome; Vomiting; Young Adult
PubMed: 23893277
DOI: 10.1136/bcr-2013-010473 -
Frontiers in Immunology 2021The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator () gene, located in the chromosomal region 21q22.3. The... (Review)
Review
The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator () gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)-chronic mucocutaneous candidiasis-autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.
Topics: Addison Disease; Adolescent; Adult; Age of Onset; Animals; Autoantigens; Autoimmune Diseases; Autoimmunity; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Disease Management; Disease Models, Animal; Disease Susceptibility; Female; Humans; Immunity, Cellular; Immunity, Humoral; Infant; Infant, Newborn; Male; Middle Aged; Phenotype; Polyendocrinopathies, Autoimmune; Prevalence; Proteomics; Young Adult
PubMed: 33717087
DOI: 10.3389/fimmu.2021.606860 -
British Medical Journal Jun 1970
Topics: Addison Disease; Diet Fads; Female; Glycyrrhiza; Humans; Plants, Medicinal; Sodium
PubMed: 5429668
DOI: 10.1136/bmj.2.5711.733 -
Frontiers in Endocrinology 2023X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder caused by a congenital defect in the ATP-binding cassette transporters... (Review)
Review
X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder caused by a congenital defect in the ATP-binding cassette transporters sub-family D member 1 gene (ABCD1) producing adrenoleukodystrophy protein (ALDP). According to population studies, X-ALD has an estimated birth prevalence of 1 in 17.000 subjects (considering both hemizygous males and heterozygous females), and there is no evidence that this prevalence varies among regions or ethnic groups. ALDP deficiency results in a defective peroxisomal β-oxidation of very long chain fatty acids (VLCFA). As a consequence of this metabolic abnormality, VLCFAs accumulate in nervous system (brain white matter and spinal cord), testis and adrenal cortex. All X-ALD affected patients carry a mutation on the ABCD1 gene. Nevertheless, patients with a defect on the ABCD1 gene can have a dramatic difference in the clinical presentation of the disease. In fact, X-ALD can vary from the most severe cerebral paediatric form (CerALD), to adult adrenomyeloneuropathy (AMN), Addison-only and asymptomatic forms. Primary adrenal insufficiency (PAI) is one of the main features of X-ALD, with a prevalence of 70% in ALD/AMN patients and 5% in female carriers. The pathogenesis of X-ALD related PAI is still unclear, even if a few published data suggests a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of adrenal cell membrane function and ACTH receptor activity. The reason why PAI develops only in a proportion of ALD/AMN patients remains incompletely understood. A growing consensus supports VLCFA assessment in all male children presenting with PAI, as early diagnosis and start of therapy may be essential for X-ALD patients. Children and adults with PAI require individualized glucocorticoid replacement therapy, while mineralocorticoid therapy is needed only in a few cases after consideration of hormonal and electrolytes status. Novel approaches, such as prolonged release glucocorticoids, offer potential benefit in optimizing hormonal replacement for X-ALD-related PAI. Although the association between PAI and X-ALD has been observed in clinical practice, the underlying mechanisms remain poorly understood. This paper aims to explore the multifaceted relationship between PAI and X-ALD, shedding light on shared pathophysiology, clinical manifestations, and potential therapeutic interventions.
Topics: Adult; Humans; Male; Female; Child; Adrenoleukodystrophy; ATP-Binding Cassette Transporters; Addison Disease; Fatty Acids; Adrenal Cortex; Glucocorticoids
PubMed: 38034003
DOI: 10.3389/fendo.2023.1309053 -
European Journal of Endocrinology Aug 2023Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2,...
OBJECTIVE
Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.
DESIGN
Case-control study on patients with AAD and healthy controls.
METHODS
Using next-generation DNA sequencing, we estimated the copy number of CYP21A2 and CYP21A1P, together with HLA alleles, in 479 Swedish patients with AAD and autoantibodies against 21-hydroxylase and in 1393 healthy controls.
RESULTS
With 95% of individuals carrying 2 functional 21-hydroxylase genes, no difference in CYP21A2 copy number was found when comparing patients and controls. In contrast, we discovered a lower copy number of the pseudogene CYP21A1P among AAD patients (P = 5 × 10-44), together with associations of additional nucleotide variants, in the CYP21 region. However, the strongest association was found for HLA-DQB1*02:01 (P = 9 × 10-63), which, in combination with the DRB1*04:04-DQB1*03:02 haplotype, imposed the greatest risk of AAD.
CONCLUSIONS
We identified strong associations between copy number variants in the CYP21 region and risk of AAD, although these associations most likely are due to linkage disequilibrium with disease-associated HLA class II alleles.
Topics: Humans; Addison Disease; Steroid 21-Hydroxylase; DNA Copy Number Variations; Case-Control Studies; Sweden; Autoantibodies
PubMed: 37553728
DOI: 10.1093/ejendo/lvad102 -
BMJ (Clinical Research Ed.) Apr 1996
Topics: Addison Disease; Adult; Autoimmune Diseases; Autopsy; Fatal Outcome; Female; Humans; Male
PubMed: 8616420
DOI: 10.1136/bmj.312.7038.1085 -
Indian Pediatrics Sep 2003
Topics: Addison Disease; Child; Humans; Hyperpigmentation; Male
PubMed: 14530557
DOI: No ID Found -
The Netherlands Journal of Medicine Aug 2002Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated... (Review)
Review
Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly.
Topics: Addison Disease; Autoimmune Diseases; Autoimmunity; Humans; Polyendocrinopathies, Autoimmune
PubMed: 12430572
DOI: No ID Found -
Endocrine Dec 2017The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In...
PURPOSE
The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins.
METHODS
A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies.
RESULTS
We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs.
CONCLUSIONS
The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.
Topics: Addison Disease; Adolescent; Adult; Aged; Autoimmune Diseases; Child; Cloning, Molecular; Cohort Studies; DNA, Complementary; Female; Genetic Predisposition to Disease; Humans; Longitudinal Studies; Male; Middle Aged; Prevalence; Registries; Sweden; Twins, Dizygotic; Twins, Monozygotic; Young Adult
PubMed: 29039147
DOI: 10.1007/s12020-017-1441-z -
British Medical Journal Feb 1952
Topics: Addison Disease; Adrenal Insufficiency; Female; Humans; Hypoadrenocorticism, Familial; Pregnancy; Pregnancy Complications
PubMed: 14896170
DOI: 10.1136/bmj.1.4755.421