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Reumatologia 2023Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes, are a group of autoimmune diseases characterized by the co-occurrence of... (Review)
Review
Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes, are a group of autoimmune diseases characterized by the co-occurrence of dysfunctions of several (at least two) endocrine glands. They develop under the influence of environmental factors in genetically predisposed people. Autoimmune polyendocrine syndromes may accompany autoimmune rheumatic diseases and worsen their course - APS-2 and APS-3 are the most common. The APS-2 includes the coexistence of, e.g. Hashimoto's disease, celiac disease and rheumatoid arthritis (RA). In APS-3, rheumatic diseases such as RA, systemic lupus erythematosus, and Sjögren's syndrome may coexist with Hashimoto's disease, type 1 diabetes and hypogonadism or other endocrinopathies. Undiagnosed endocrine diseases may be the reason for the intensification of metabolic disorders observed in the course of rheumatic diseases, cause the ineffectiveness of rheumatological treatment and also increase the frequency of bone fractures due to osteoporosis, cardiovascular complications and even miscarriages when coexistent, e.g. Hashimoto's disease with hypothyroiditis, which increases the risk of pregnancy loss. It is important to be able to conduct an extensive interview, paying attention to the symptoms of possible endocrinopathy as well as the features of other autoimmune disorders in the physical examination (e.g. vitiligo or darkening of the skin in Addison's disease). Depending on the history and physical examination, screening for various APSs is advised.
PubMed: 37745144
DOI: 10.5114/reum/170266 -
The New England Journal of Medicine Jun 2021
Topics: Addison Disease; Adult; Female; Humans; Hydrocortisone; Pigmentation Disorders; Tongue; Tongue Diseases
PubMed: 34161701
DOI: 10.1056/NEJMicm2100706 -
The Journal of Clinical Endocrinology... Apr 2020The CXC chemokine receptor CXCR3 and its chemokines CXCL10, CXCL9, and CXCL11 are implicated in the pathogenesis of autoimmune diseases. Here, we review these chemokines... (Review)
Review
CONTEXT
The CXC chemokine receptor CXCR3 and its chemokines CXCL10, CXCL9, and CXCL11 are implicated in the pathogenesis of autoimmune diseases. Here, we review these chemokines in autoimmune thyroiditis (AT), Graves disease (GD), thyroid eye disease (TED), type 1 diabetes (T1D), and Addison's disease (AAD).
EVIDENCE ACQUISITION
A PubMed review of the literature was conducted, searching for the above-mentioned chemokines in combination with AT, GD, TED, T1D, and AAD.
EVIDENCE SYNTHESIS
Thyroid follicular cells in AT and GD, retroorbital cells in TED (fibroblasts, preadipocytes, myoblasts), β cells and islets in T1D, and adrenal cells in AAD respond to interferon-γ (IFN-γ) stimulation producing large amounts of these chemokines. Furthermore, lymphocytes and peripheral blood mononuclear cells (PBMC) are in part responsible for the secreted Th1 chemokines. In AT, GD, TED, T1D, and AAD, the circulating levels of these chemokines have been shown to be high. Furthermore, these chemokines have been associated with the early phases of the autoimmune response in all the above-mentioned disorders. High levels of these chemokines have been associated also with the "active phase" of the disease in GD, and also in TED. Other studies have shown an association with the severity of hypothyroidism in AD, of hyperthyroidism in GD, with severity of TED, or with fulminant T1D.
CONCLUSION
The reviewed data have shown the importance of the Th1 immune response in different endocrine autoimmune diseases, and many studies have suggested that CXCR3 and its chemokines might be considered as potential targets of new drugs for the treatment of these disorders.
Topics: Autoimmune Diseases; Chemokines; Endocrine System Diseases; Humans; Prognosis; Th1 Cells
PubMed: 31863667
DOI: 10.1210/clinem/dgz289 -
SAGE Open Medical Case Reports 2021This case report highlights the initial presentation of Addison's disease in a 19-year-old individual with coronavirus disease. Coronavirus disease is an infectious...
This case report highlights the initial presentation of Addison's disease in a 19-year-old individual with coronavirus disease. Coronavirus disease is an infectious disease, which often presents with fever and respiratory and gastrointestinal symptoms. Here, we describe a challenging case of a patient with coronavirus disease, who initially presented with altered mental status, hyponatremia, and cerebral edema, with subsequent workup leading to the diagnosis of Addison's disease.
PubMed: 35154776
DOI: 10.1177/2050313X211027758 -
Deutsche Medizinische Wochenschrift... Jan 2022Addison's disease typically results from the autoimmune destruction of the adrenal cortex and requires lifelong replacement with glucocorticoids and mineralocorticoids....
Addison's disease typically results from the autoimmune destruction of the adrenal cortex and requires lifelong replacement with glucocorticoids and mineralocorticoids. Main symptoms are non-specific and, therefore, often overlooked or misleading. Patients are frequently not diagnosed until experiencing a life-threatening adrenal crisis. This article highlights the essential clinical characteristics, diagnostic aspects and principles of management of adrenal insufficiency.
Topics: Addison Disease; Adrenal Cortex; Adrenal Gland Diseases; Adrenal Insufficiency; Glucocorticoids; Humans
PubMed: 35100642
DOI: 10.1055/a-1370-5874 -
Deutsche Medizinische Wochenschrift... Dec 2019We report the case within a 22-year-old patient, initially seen because of fatigue, weight loss and discoloration of the skin. A Hashimoto-Thyroditis had been diagnosed...
HISTORY AND CLINICAL FINDINGS
We report the case within a 22-year-old patient, initially seen because of fatigue, weight loss and discoloration of the skin. A Hashimoto-Thyroditis had been diagnosed a few months prior to the clinical presentation.
DIAGNOSTICS
Blood samples showed a hyponatremia and hyperkalemia. Addison's disease was diagnosed by management of cortisol, ACTH and adrenal antibodies. In combination with the previously diagnosed Autoimmune thyreoiditis the criteria for a Schmidt's Syndrome were fulfilled.
TREATMENT AND CLINICAL COURSE
We initiated the substitution of Hydrocortisone (20 mg/d) and Fludrocortisone (0.1 mg/d) in combination with an increased levothyroxin-dosage (100 µg/d). The patient's condition improved over the course of a few days.
CONCLUSION
The presented case underlines the importance of focused examinations and diagnostics when dealing with a patient with unspecific symptoms and a pre-existing autoimmune disease. This also applies to patients with a positive family history for autoimmune disorders.
Topics: Addison Disease; Adult; Cortisone; Female; Hashimoto Disease; Humans; Hyperkalemia; Hyponatremia; Polyendocrinopathies, Autoimmune; Thyroxine; Young Adult
PubMed: 31791082
DOI: 10.1055/a-0875-4538 -
The Journal of Clinical Endocrinology... Feb 2020Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed...
CONTEXT
Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.
OBJECTIVE
To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.
DESIGN
Retrospective cohort study using UK data collected from 1995 to 2018.
MAIN OUTCOME MEASURES
Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls.
RESULTS
A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]).
CONCLUSIONS
There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.
Topics: Addison Disease; Adrenal Hyperplasia, Congenital; Adult; Disease Susceptibility; Female; Glucocorticoids; Humans; Incidence; Infections; Male; Middle Aged; Primary Health Care; Retrospective Studies; Risk Factors; United Kingdom
PubMed: 31532828
DOI: 10.1210/clinem/dgz006 -
Nature Reviews. Endocrinology Jul 2022Autoimmune Addison disease is an endocrinopathy that is fatal if not diagnosed and treated in a timely manner. Its rarity has hampered unbiased studies of the... (Review)
Review
Autoimmune Addison disease is an endocrinopathy that is fatal if not diagnosed and treated in a timely manner. Its rarity has hampered unbiased studies of the predisposing genetic factors. A 2021 genome-wide association study, explaining up to 40% of the genetic susceptibility, has revealed new disease loci and reproduced some of the previously reported associations, while failing to reproduce others. Credible risk loci from both candidate gene and genome-wide studies indicate that, like one of its most common comorbidities, type 1 diabetes mellitus, Addison disease is primarily caused by aberrant T cell behaviour. Here, we review the current understanding of the genetics of autoimmune Addison disease and its position in the wider field of autoimmune disorders. The mechanisms that could underlie the effects on the adrenal cortex are also discussed.
Topics: Addison Disease; Autoimmune Diseases; Diabetes Mellitus, Type 1; Endocrine System Diseases; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans
PubMed: 35411072
DOI: 10.1038/s41574-022-00653-y -
European Journal of Endocrinology Oct 2023Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.
OBJECTIVE
Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.
DESIGN
Cross-sectional study.
METHODS
We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.
RESULTS
Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).
CONCLUSIONS
We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.
Topics: Humans; Male; Female; Addison Disease; Cross-Sectional Studies; Quality of Life; Leptin; Glucocorticoids; Cardiovascular Diseases; Inflammation; Cosyntropin; Biomarkers; Neoplasm Proteins; Extracellular Matrix Proteins
PubMed: 37807083
DOI: 10.1093/ejendo/lvad136 -
The Lancet. Diabetes & Endocrinology May 2020
Topics: Addison Disease; Female; Glucocorticoids; Humans; Hyperpigmentation; Middle Aged
PubMed: 32192601
DOI: 10.1016/S2213-8587(20)30076-0