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Experimental and Clinical Endocrinology... Feb 2019Addison's disease - the traditional term for primary adrenal insufficiency (PAI) - is defined as the clinical manifestation of chronic glucocorticoid- and/or... (Review)
Review
Addison's disease - the traditional term for primary adrenal insufficiency (PAI) - is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common "classical" causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions - mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.
Topics: Addison Disease; Humans
PubMed: 30562824
DOI: 10.1055/a-0804-2715 -
Journal of Internal Medicine Feb 2014Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction... (Review)
Review
Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow-up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21-hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life-threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow-up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self-adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow-up.
Topics: Acute Disease; Addison Disease; Adrenal Cortex; Adrenal Insufficiency; Algorithms; Autoantibodies; Autoimmunity; Chronic Disease; Consensus; Cortisone; Diagnosis, Differential; Drug Administration Schedule; Drug Interactions; Emergency Treatment; Europe; Female; Humans; Hydrocortisone; Male; Prednisolone; Pregnancy; Pregnancy Complications; Steroid 21-Hydroxylase
PubMed: 24330030
DOI: 10.1111/joim.12162 -
American Family Physician Apr 2014Primary adrenal insufficiency, or Addison disease, has many causes, the most common of which is autoimmune adrenalitis. Autoimmune adrenalitis results from destruction...
Primary adrenal insufficiency, or Addison disease, has many causes, the most common of which is autoimmune adrenalitis. Autoimmune adrenalitis results from destruction of the adrenal cortex, which leads to deficiencies in glucocorticoids, mineralocorticoids, and adrenal androgens. In the United States and Western Europe, the estimated prevalence of Addison disease is one in 20,000 persons; therefore, a high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis (i.e., shock, hypotension, and volume depletion). The clinical manifestations before an adrenal crisis are subtle and can include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving. Cortisol levels decrease and adrenocorticotropic hormone levels increase. When clinically suspected, patients should undergo a cosyntropin stimulation test to confirm the diagnosis. Treatment of primary adrenal insufficiency requires replacement of mineralocorticoids and glucocorticoids. During times of stress (e.g., illness, invasive surgical procedures), stress-dose glucocorticoids are required because destruction of the adrenal glands prevents an adequate physiologic response. Management of primary adrenal insufficiency or autoimmune adrenalitis requires vigilance for concomitant autoimmune diseases; up to 50% of patients develop another autoimmune disorder during their lifetime.
Topics: Addison Disease; Adrenal Glands; Diagnosis, Differential; Hormone Replacement Therapy; Humans
PubMed: 24695602
DOI: No ID Found -
Clinical Endocrinology Jan 2020Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires urgent diagnosis and treatment. Whilst the most common causes are... (Review)
Review
Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires urgent diagnosis and treatment. Whilst the most common causes are congenital adrenal hyperplasia (CAH) in childhood and autoimmune adrenal insufficiency in adolescence and adulthood, more than 30 other physical and genetics cause of PAI have been reported. Reaching a specific diagnosis can have implications for management and for monitoring associated features, as well as for counselling families about recurrence risk in siblings and relatives. Here, we describe some recent insights into the genetics of adrenal insufficiency and associated molecular mechanisms. 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). Reaching a specific diagnosis can have life-long implications for management. In some situations, milder or nonclassic forms of these conditions can first present in adulthood and may have been labelled, "Addison's disease."
Topics: Addison Disease; Humans
PubMed: 31610036
DOI: 10.1111/cen.14109 -
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 -
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 -
Proceedings of the Royal Society of... Apr 1954
Topics: Addison Disease; Adrenal Insufficiency; Goiter; Humans; Hypoadrenocorticism, Familial
PubMed: 13155529
DOI: No ID Found -
British Medical Journal Jul 1979
Topics: Addison Disease; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortisone; History, 20th Century; Humans; Skin Pigmentation
PubMed: 223716
DOI: 10.1136/bmj.2.6181.25 -
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 -
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