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European Journal of Internal Medicine Aug 2018
Topics: Addison Disease; Adult; Diagnosis, Differential; Disease Management; Female; Glucocorticoids; Humans; Hyperpigmentation
PubMed: 29325793
DOI: 10.1016/j.ejim.2017.12.015 -
The Journal of Clinical Endocrinology... May 2022Autoimmune thyroid disease is the most common endocrine comorbidity in autoimmune Addison disease (AAD), but detailed investigations of prevalence and clinical course...
CONTEXT
Autoimmune thyroid disease is the most common endocrine comorbidity in autoimmune Addison disease (AAD), but detailed investigations of prevalence and clinical course are lacking.
OBJECTIVE
This work aimed to provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD.
METHODS
A nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease were identified through the Norwegian National Registry of Autoimmune Diseases.
RESULTS
Of 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. A total of 380 (42%) had autoimmune hypothyroidism. Of the 203 with available thyroid function tests at time of diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism, and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up, 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%).
CONCLUSION
The true prevalence of hypothyroidism in AAD is lower than reported in the current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD.
Topics: Addison Disease; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Thyroid Hormones; Thyroiditis, Autoimmune; Thyroxine
PubMed: 35226748
DOI: 10.1210/clinem/dgac089 -
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 -
Clinical Endocrinology Jun 2017Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor... (Review)
Review
Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome.
Topics: Addison Disease; Anxiety Disorders; Depressive Disorder; Endocrine System Diseases; Female; Humans; Male; Polycystic Ovary Syndrome; Psychological Techniques; Quality of Life; Stress, Psychological
PubMed: 28370206
DOI: 10.1111/cen.13341 -
Frontiers in Immunology 2023Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have...
INTRODUCTION
Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency.
METHODS
This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated.
RESULTS
The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected.
DISCUSSION
In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.
Topics: Humans; Addison Disease; Cross-Sectional Studies; Leukocytes, Mononuclear; Cushing Syndrome; Glucocorticoids; Hydrocortisone; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency
PubMed: 38045693
DOI: 10.3389/fimmu.2023.1275828 -
Internal Medicine (Tokyo, Japan) 2016We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory...
We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands.
Topics: Addison Disease; Adrenal Glands; Diagnosis, Differential; Fatigue; Granuloma; Humans; Hyponatremia; Lymphatic Diseases; Male; Middle Aged; Peptidyl-Dipeptidase A; Sarcoidosis
PubMed: 27150885
DOI: 10.2169/internalmedicine.55.5392 -
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 -
Journal of Clinical Research in... Aug 2022Primary adrenal insufficiency (PAI) is a rare condition in children, and is potentially life-threatening. The most common cause is congenital adrenal hyperplasia, and...
OBJECTIVE
Primary adrenal insufficiency (PAI) is a rare condition in children, and is potentially life-threatening. The most common cause is congenital adrenal hyperplasia, and autoimmune etiology is the most frequent acquired cause in this age group. Symptoms are usually non-specific and, when suspected, investigation should include adrenocorticotropin hormone (ACTH) and morning serum cortisol measurement and, in some cases, a cosyntropin test to confirm the diagnosis. Prompt treatment is essential to prevent an adverse outcome.
METHODS
We retrospectively collected clinical and laboratory data from adrenal insufficiency due to autoimmune adrenalitis, observed from 2015 to 2020 in a pediatric endocrinology department of a tertiary care hospital.
RESULTS
Eight patients were identified, seven males and one female, with age at diagnosis between 14 and 17 years. The symptoms at presentation ranged from non-specific symptoms, such as chronic fatigue and weight loss, to a severe presentation, with altered mental status and seizures. The median duration of symptoms was 4.5 months. The diagnosis was confirmed by serum cortisol and plasma ACTH measurement and all were confirmed to have autoimmune etiology (positive anti-adrenal antibodies). At diagnosis, the most common laboratory abnormality was hyponatremia. All patients were treated with hydrocortisone and fludrocortisone. One patient presented with evidence of type 2 autoimmune polyglandular syndrome.
CONCLUSION
PAI is a rare condition in the pediatric age group. Due to non-specific symptoms, a high index of suspicion is necessary to establish a prompt diagnosis. Once an autoimmune etiology is confirmed, it is important to initiate the appropriate treatment and search for signs and symptoms of other autoimmune diseases during follow-up.
Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Female; Humans; Hydrocortisone; Male; Retrospective Studies
PubMed: 35633647
DOI: 10.4274/jcrpe.galenos.2022.2021-11-9 -
Cureus Feb 2021Addison's disease is a rare and potentially life-threatening clinical condition that often presents with an insidious onset of nonspecific symptoms and signs, frequently...
Addison's disease is a rare and potentially life-threatening clinical condition that often presents with an insidious onset of nonspecific symptoms and signs, frequently resulting in a significant delay in diagnosis. Clinical presentation usually includes fatigue and electrolyte imbalance disorders such as hyponatremia. However, specific diagnostic features, such as hyperpigmentation, should raise clinical suspicion. This case report describes a 43-year-old Caucasian male who presented with general malaise, fatigue, anorexia, and weight loss (7 Kg in four weeks). On physical examination, he was found to have severe hyperpigmentation of the skin and mucosal surfaces as well as hypotension. Laboratory tests revealed hypoosmolar hyponatremia and serum potassium levels in the upper limit of normal. Findings of high serum adrenocorticotropic hormone (ACTH) and renin, as well as low cortisol and aldosterone levels, helped establish a diagnosis of Addison's disease. After the initiation of treatment, the patient experienced full recovery of symptoms, normalization of hyponatremia, and improvement of hyperpigmentation. Patients with Addison's disease have the potential to resume normal daily activities with a highly functional status. However, this condition requires lifelong follow-up and surveillance.
PubMed: 33747659
DOI: 10.7759/cureus.13364 -
BMC Genomics Nov 2020Primary hypoadrenocorticism (or Addison's disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency....
BACKGROUND
Primary hypoadrenocorticism (or Addison's disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies.
RESULTS
Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility.
CONCLUSION
Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.
Topics: Addison Disease; Animals; Dog Diseases; Dogs; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Polymorphism, Single Nucleotide
PubMed: 33243158
DOI: 10.1186/s12864-020-07243-0