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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 -
Scandinavian Journal of Immunology Nov 2020The new era of immune and reconstitution therapy of autoimmune disorders is ongoing. However, endocrine autoimmune diseases comprise a group of elaborating pathologies... (Review)
Review
The new era of immune and reconstitution therapy of autoimmune disorders is ongoing. However, endocrine autoimmune diseases comprise a group of elaborating pathologies where the development of new treatment strategies remains slow. Substitution of the missing hormones is still standard practice, taking care of the devastating symptoms but not the cause of disease. As our knowledge of the genetic contribution to the aetiology of endocrine disorders increases and early diagnostic tools are available, it is now possible to identify persons at risk before they acquire full-blown disease. This review summarizes current knowledge and treatment of endocrine autoimmune disorders, focusing on type 1 diabetes, Addison's disease, autoimmune thyroid diseases and primary ovarian insufficiency. We explore which new therapies might be used in the different stages of the disease, focus on legalized therapy and elaborate on the ongoing clinical studies for these diseases and the research front, before hypothesizing on the way ahead.
Topics: Addison Disease; Autoimmune Diseases; Diabetes Mellitus, Type 1; Endocrine System Diseases; Female; Humans; Immunotherapy; Models, Immunological; Primary Ovarian Insufficiency; Thyroid Diseases
PubMed: 32853446
DOI: 10.1111/sji.12961 -
BMJ Case Reports Mar 2018A 67-year-old Caucasian woman with no prior medical history was admitted to our hospital with complaints of generalised weakness, nausea, diarrhoea and weight loss. The...
A 67-year-old Caucasian woman with no prior medical history was admitted to our hospital with complaints of generalised weakness, nausea, diarrhoea and weight loss. The patient suffered from tachycardia and hypotension. Blood tests revealed Graves' thyrotoxicosis and the patient was treated accordingly. However, patient's health continued to decline rapidly and further tests revealed a concomitant Addisonian crisis. Additional treatment with corticosteroids led to a full recovery. It is well known that autoimmune endocrine disorders tend to cluster. However, the presentation is usually sequential in time. This case reports the highly rare simultaneous presentation of Addison's disease and Graves' thyrotoxicosis. It also provides several suggestions to help establish the diagnoses.
Topics: Addison Disease; Adrenocorticotropic Hormone; Aged; Biomarkers; Blood Urea Nitrogen; Creatinine; Female; Graves Disease; Humans; Thyrotoxicosis
PubMed: 29507013
DOI: 10.1136/bcr-2017-222355 -
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 -
Cerebral Cortex (New York, N.Y. : 1991) Apr 2023Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white...
Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white matter brain structure in a cohort of young adults with AAD. T1- and diffusion-weighted images were acquired for 52 individuals with AAD and 70 healthy controls, aged 19-43 years, using magnetic resonance imaging. Groups were compared on cortical thickness, surface area, cortical gray matter volume, subcortical volume (FreeSurfer), and white matter microstructure (FSL tract-based spatial statistics). Individuals with AAD had 4.3% smaller total brain volume. Correcting for head size, we did not find any regional structural differences, apart from reduced volume of the right superior parietal cortex in males with AAD. Within the patient group, a higher glucocorticoid (GC) replacement dose was associated with smaller total brain volume and smaller volume of the left lingual gyrus, left rostral anterior cingulate cortex, and right supramarginal gyrus. With the exception of smaller total brain volume and potential sensitivity of the parietal cortex to GC disturbances in men, brain structure seems relatively unaffected in young adults with AAD. However, the association between GC replacement dose and reduced brain volume may be reason for concern and requires follow-up study.
Topics: Male; Young Adult; Humans; Addison Disease; Follow-Up Studies; Brain; Gray Matter; Magnetic Resonance Imaging
PubMed: 36227196
DOI: 10.1093/cercor/bhac389 -
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 -
The Canadian Veterinary Journal = La... Jan 2010Hypoadrenocorticism (Addison's disease) has been referred to as "the great pretender," due to its ability to mimic other common diseases in the dog and thereby represent... (Review)
Review
Hypoadrenocorticism (Addison's disease) has been referred to as "the great pretender," due to its ability to mimic other common diseases in the dog and thereby represent a diagnostic challenge. Naturally occurring hypoadrenocorticism is an uncommon canine disease. Young, female dogs are overrepresented. Hypoadrenocorticism typically results from immune-mediated destruction of all adrenocortical layers, resulting in deficiencies of min-eralocorticoids (aldosterone) and glucocorticoids (cortisol). A small number of dogs suffer from glucocorticoid deficiency only. Dogs suffering from hypoadrenocorticism may present in a variety of conditions, from a mildly ill dog to a shocky and recumbent dog. This review discusses etiology, pathophysiology, history, physical examination findings, and diagnostic findings in the Addisonian patient. A follow-up article (Part II) will discuss the definitive diagnosis and management strategies for these patients.
Topics: Addison Disease; Age Factors; Aldosterone; Animals; Dog Diseases; Dogs; Female; Hydrocortisone; Male; Physical Examination; Sex Factors
PubMed: 20357943
DOI: No ID Found -
Frontiers in Endocrinology 2021Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption... (Review)
Review
Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison's disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients' cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.
Topics: Addison Disease; Cognition; Humans; Hydrocortisone; Memory Disorders; Quality of Life; Risk Factors; Signal Transduction; Sleep
PubMed: 34512546
DOI: 10.3389/fendo.2021.694046 -
The Veterinary Clinics of North... Apr 2011The adrenal cortices produce various steroid hormones that play vital roles in several physiologic processes. Although permanent adrenocortical insufficiency is rare in... (Review)
Review
The adrenal cortices produce various steroid hormones that play vital roles in several physiologic processes. Although permanent adrenocortical insufficiency is rare in all species, emerging evidence in both human and equine medicine suggests that transient reversible adrenocortical dysfunction resulting in cortisol insufficiency frequently develops during critical illness. This syndrome is termed relative adrenal insufficiency (RAI) or critical illness-related corticosteroid insufficiency (CIRCI) and can contribute substantially to morbidity and mortality associated with the primary disease. This review discusses the mechanisms, diagnosis, and clinical consequences of adrenocortical insufficiency, with particular focus on the current understanding of RAI/CIRCI in horses and foals.
Topics: Addison Disease; Adrenal Cortex; Animals; Animals, Newborn; Female; Horse Diseases; Horses; Hydrocortisone; Male
PubMed: 21392651
DOI: 10.1016/j.cveq.2010.12.005 -
Revista Da Associacao Medica Brasileira... Dec 2019Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes...
Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes mellitus (T1DM). It is a rare disease, affecting about 1.4-2 cases/100,000 inhabitants. Its less frequent clinical presentation is the combination of AD, Graves' disease, and T1DM. We present the case of a 42-year-old woman with a history of total thyroidectomy due to Graves' disease, type 2 diabetes mellitus, and hypertension, who sought the ED due to asthenia, dizziness, nausea, and vomiting. She reported having stopped antihypertensive therapy due to hypotension and presented a glycemic record with frequent hypoglycemia. On physical examination, she had cutaneous hyperpigmentation. She had no leukocytosis, anemia, hypoglycemia, hyponatremia or hyperkalemia, and a negative PCR. Serum cortisol <0.5 ug/dl (4,3-22,4), urine free cortisol 9 ug/24h (28-214), ACTH 1384 pg/mL (4,7-48,8), aldosterone and renin in erect position of 0 pg/ml (41-323) and 430.7 uUI/ml (4.4-46.1) respectively. Quantiferon TB was negative; computerized axial tomography of the adrenals showed no infiltrations, hemorrhage, or masses. The 21-hydroxylase antibody assay was positive. B12 vitamin was normal, anti-GAD antibodies were positive, anti-insulin, anti-IA2, and anti-transglutaminase antibodies were all negative. The patient started insulin therapy and treatment for AD with prednisolone and fludrocortisone with good clinical response. This case aims to alert to the need for high clinical suspicion in the diagnosis of AD. Since this is a rare autoimmune disease, it is important to screen for other autoimmune diseases in order to exclude APS.
Topics: Addison Disease; Adult; Diabetes Mellitus, Type 1; Early Diagnosis; Female; Graves Disease; Humans; Polyendocrinopathies, Autoimmune; Rare Diseases; Treatment Outcome
PubMed: 31994621
DOI: 10.1590/1806-9282.65.12.1434