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British Medical Journal Nov 1971
Topics: Addison Disease; Asthma; Automobile Driving; Death, Sudden; Humans; Male; Physical Exertion
PubMed: 5126967
DOI: 10.1136/bmj.4.5786.560-f -
European Journal of Endocrinology Apr 2021The most common cause of primary adrenal failure (Addison's disease) in the Western world is autoimmunity characterized by autoantibodies against the steroidogenic...
BACKGROUND
The most common cause of primary adrenal failure (Addison's disease) in the Western world is autoimmunity characterized by autoantibodies against the steroidogenic enzyme 21-hydroxylase (CYP21A2, 21OH). Detection of 21OH-autoantibodies is currently used for aetiological diagnosis, but how levels of 21OH-autoantibodies vary over time is not known.
SETTING
Samples from the national Norwegian Addison's Registry and Biobank established in 1996 (n = 711). Multi-parameter modelling of the course of 21OH-autoantibody indices over time.
RESULTS
21OH-autoantibody positivity is remarkably stable, and >90% of the patients are still positive 30 years after diagnosis. Even though the antibody levels decline with disease duration, it is only rarely that this downturn reaches negativity. 21OH-autoantibody indices are affected by age at diagnosis, sex, type of Addison's disease (isolated vs autoimmune polyendocrine syndrome type I or II) and HLA genotype.
CONCLUSION
21OH-autoantibodies are reliable and robust markers for autoimmune Addison's disease, linked to HLA risk genotype. However, a negative test in patients with long disease duration does not exclude autoimmune aetiology.
Topics: Addison Disease; Adolescent; Adult; Autoantibodies; Biomarkers; Cohort Studies; Female; Humans; Male; Middle Aged; Steroid 21-Hydroxylase; Young Adult
PubMed: 34665570
DOI: 10.1530/EJE-20-1268 -
Journal of Medical Case Reports Mar 2021Primary adrenal insufficiency (Addison's disease) is a rare medical condition usually associated with hyperkalemia or normokalemia. We report a rare case of Addison's...
BACKGROUND
Primary adrenal insufficiency (Addison's disease) is a rare medical condition usually associated with hyperkalemia or normokalemia. We report a rare case of Addison's disease, coexisting with hypokalemia, requiring treatment.
CASE PRESENTATION
In this case, a 42-year-old man was admitted to the intensive care unit with a history of loss of consciousness and severe hypoglycemia. His blood tests showed metabolic acidosis, low concentrations of cortisol 6 nmol/L (normal 68-327 nmol/L), and high plasma adrenocorticotropic hormone 253 pmol/L (normal 1.6-13.9 pmol/L), and he was diagnosed with primary adrenal insufficiency. Surprisingly, his serum potassium was low, 2.3 mmol/L (normal 3.5-5.1 mmol/L), requiring replacement over the course of his admission. Computed tomography scan of the adrenal glands showed features suggestive of unilateral adrenal tuberculosis. Investigations confirmed renal tubulopathy. The patient responded favorably to cortisol replacement, but never required fludrocortisone.
CONCLUSIONS
Coexistence of hypokalemia with Addison's disease is unusual. We recommend investigation of the cause of hypokalemia in its own right, if it occurs with primary adrenal insufficiency.
Topics: Addison Disease; Adrenal Glands; Adult; Fludrocortisone; Humans; Hydrocortisone; Hypokalemia; Male
PubMed: 33761983
DOI: 10.1186/s13256-021-02724-6 -
The Journal of Clinical Endocrinology... May 2019Multiple autosomal recessive genes have been etiologically linked to primary adrenal insufficiency (PAI). Recently, sphingosine-1-phosphate lyase 1 (SGPL1) gene...
CONTEXT
Multiple autosomal recessive genes have been etiologically linked to primary adrenal insufficiency (PAI). Recently, sphingosine-1-phosphate lyase 1 (SGPL1) gene mutations were recognized as a cause of steroid-resistant nephrotic syndrome type 14 (NPHS14), a sphingolipidosis with multisystemic manifestations, including PAI.
OBJECTIVE
To check if SGPL1 mutations are involved in the pathogenesis of PAI in patients who do not exhibit nephrotic syndrome.
METHODS
Sequencing of the SGPL1 gene in 21 patients with familial glucocorticoid disease or triple A syndrome.
RESULTS
We identified two missense SGPL1 variants in four patients, two of whom were first cousins. We describe in detail the proband, a boy born to Saudi Arabian consanguineous parents with a homozygous c.665G>A, p.R222Q SGPL1 variant. The patient presented with hypoglycemia and seizures at age 2 years and was ultimately diagnosed with PAI (isolated glucocorticoid deficiency). Brain MRI showed abnormalities in the basal ganglia consistent with a degenerative process albeit the patient had no neurologic symptoms.
CONCLUSIONS
New genetic causes of PAI continue to be identified. We suggest that screening for SGPL1 mutations should not be reserved only for patients with nephrotic syndrome but may also include patients with PAI who lack other clinical manifestations of NPHS14 because, in certain cases, kidney disease and accompanying features might develop. Timely diagnosis of this specific sphingolipidosis while the kidneys still function normally can lead to prompt initiation of therapy and improve outcome.
Topics: Addison Disease; Adolescent; Adult; Aldehyde-Lyases; Biomarkers; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Mutation; Pedigree; Prognosis; Risk Factors
PubMed: 30517686
DOI: 10.1210/jc.2018-02238 -
International Journal of Environmental... Jul 2017Celiac disease (CD) is an autoimmune disorder deriving from an aberrant adaptive immune response against gluten-containing grains in genetically predisposed subjects. In...
BACKGROUND
Celiac disease (CD) is an autoimmune disorder deriving from an aberrant adaptive immune response against gluten-containing grains in genetically predisposed subjects. In a number of patients, CD is associated with one or more other autoimmune diseases. Primary Addison's disease (AD) and CD may co-exist, although this association is relatively uncommon in children. In addition, it is not precisely defined whether a gluten-free diet influences the course of AD.
CASE PRESENTATION
A case of CD in a 12-year-old boy presenting as acute adrenal insufficiency is described here. A gluten-free diet had a significant therapeutic role in this case, wherein most of the clinical signs and symptoms of AD disappeared in a few days. In addition, the dosage of cortisol acetate, initially administered to treat the AD, was able to be rapidly reduced.
CONCLUSION
This case highlights that CD can be associated with AD in children, and a gluten-free diet seems to positively influence the course of AD.
Topics: Addison Disease; Celiac Disease; Child; Diet, Gluten-Free; Humans; Hydrocortisone; Male
PubMed: 28758924
DOI: 10.3390/ijerph14080855 -
Hormones (Athens, Greece) 2013Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal...
OBJECTIVE
Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL).
DESIGN AND METHODS
Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed.
RESULTS
At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased.
CONCLUSIONS
Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.
Topics: Addison Disease; Adult; Aged; Biomarkers; Circadian Rhythm; Cortisone; Drug Monitoring; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Quality of Life; Saliva; Surveys and Questionnaires; Time Factors; Treatment Outcome
PubMed: 23624135
DOI: 10.1007/BF03401290 -
Journal of Clinical Research in... Feb 2021Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital...
OBJECTIVE
Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital adrenal hyperplasia (CAH) is the most common cause of childhood PAI, numerous non-CAH genetic causes have also been identified.
METHODS
Patients aged 0-18 years and diagnosed with PAI between 1998 and 2019 in a tertiary care hospital were retrospectively evaluated. After the etiologic distribution was determined, non-CAH PAI patients were evaluated in detail.
RESULTS
Seventy-three PAI patients were identified. The most common etiology was CAH (69.9%, n=51). Non-CAH etiologies accounted for 30.1% (n=22) and included adrenoleukodystrophy (ALD; n=8), familial glucocorticoid deficiency (n=3), Triple A syndrome (n=5), autoimmune adrenalitis (n=1), adrenal hypoplasia congenital (n=1), IMAGe syndrome (n=1), and other unknown etiologies (n=3). The median age at the time of AI diagnosis for non-CAH etiologies was 3.52 (0.03-15.17) years. The most frequent symptoms/clinical findings at onset were hyperpigmentation of skin (81.8%), symptoms of hypoglycemia (40.9%), and weakness/fatigue (31.8%). Hypoglycemia (50.0%), hyponatremia (36.4%) and hyperkalemia (22.7%) were prominent biochemical findings. Diagnosis of specific etiologies were proven genetically in 13 of 22 patients. A novel p.Q301* hemizygous frameshift mutation of the gene was identified in one patient.
CONCLUSION
Etiology was determined in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/ without molecular analysis of candidate genes. ALD was the most common etiology. Currently, advanced molecular analysis can be utilized to establish a specific genetic diagnosis for PAI in patients who have no specific diagnostic features.
Topics: Addison Disease; Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Female; Humans; Infant; Male; Retrospective Studies; Tertiary Care Centers
PubMed: 32938577
DOI: 10.4274/jcrpe.galenos.2020.2020.0132 -
Journal of Medical Case Reports Apr 2023Adrenal insufficiency is a life-threatening condition, and advanced gastric cancer is associated with very poor prognosis. Adrenalectomy and/or metastatic invasion of...
BACKGROUND
Adrenal insufficiency is a life-threatening condition, and advanced gastric cancer is associated with very poor prognosis. Adrenalectomy and/or metastatic invasion of the adrenal glands can cause primary adrenal insufficiency, which in turn can present with symptoms mimicking advanced cancer.
CASE PRESENTATION
Herein we report of a 68-year-old White male with a history of left adrenalectomy in conjunction with distal gastrectomy due to gastric adenocarcinoma. At the 2-year follow-up visit after cancer surgery, the patient presented with fatigue, unintentional weight loss, hyperkalemia, and a computed tomography scan with a right adrenal mass. Primary adrenal insufficiency caused by gastric cancer metastatic invasion of the remaining right adrenal gland was established and glucocorticoid therapy initiated. The patient received first line palliative chemotherapy with systemic disease control and subsequent stereotactic body radiotherapy to the right adrenal gland. More than 17 months after pathology-confirmed gastric cancer relapse, there is no clinical nor radiological evidence of active malignant disease and the patient is doing well on glucocorticoid replacement therapy.
CONCLUSIONS
This case does not only illustrate the importance of prompt and correct clinical management of adrenal insufficiency, but also that selected patients with advanced gastric cancer can gain from and achieve long-term survival using a multimodal treatment approach.
Topics: Humans; Male; Aged; Stomach Neoplasms; Glucocorticoids; Addison Disease; Adrenal Gland Neoplasms; Neoplasm Recurrence, Local; Adrenal Insufficiency; Adrenalectomy
PubMed: 37038153
DOI: 10.1186/s13256-023-03858-5 -
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 -
CMAJ : Canadian Medical Association... Nov 1985In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison's disease....
In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison's disease. Considering the importance of these works, there remains a great deal of confusion about them. Contrary to what many historians have written, a review of Addison's original publications demonstrates a firm appreciation of the distinction between pernicious anemia and adrenal insufficiency, based particularly on the discoloration of the skin in these conditions. Three major sources of possible confusion for historians who are attempting to understand Addison's views include Addison's early attempts to link pernicious anemia with disease of the suprarenal capsules, Addison's redefinition of pernicious anemia in his monograph on adrenal disease, and several confusing statements made by Wilks and Daldy in the first reprint of Addison's monograph.
Topics: Addison Disease; Anemia, Pernicious; History, 19th Century; United Kingdom
PubMed: 3902186
DOI: No ID Found