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Journal of Endocrinological... Dec 2019Addison's disease (AD) is a rare disorder and among adult population in developed countries is most commonly caused by autoimmunity. In contrast, in children genetic... (Review)
Review
BACKGROUND
Addison's disease (AD) is a rare disorder and among adult population in developed countries is most commonly caused by autoimmunity. In contrast, in children genetic causes are responsible for AD in the majority of patients.
PURPOSE
This review describes epidemiology, pathogenesis, genetics, natural history, clinical manifestations, immunological markers and diagnostic strategies in patients with AD. Standard care treatments including the management of patients during pregnancy and adrenal crises consistent with the recent consensus statement of the European Consortium and the Endocrine Society Clinical Practice Guideline are described. In addition, emerging therapies designed to improve the quality of life and new strategies to modify the natural history of autoimmune AD are discussed.
CONCLUSIONS
Progress in optimizing replacement therapy for patients with AD has allowed the patients to lead a normal life. However, continuous education of patients and health care professionals of ever-present danger of adrenal crisis is essential to save lives of patients with AD.
Topics: Addison Disease; Adrenal Cortex Hormones; Adult; Age Factors; Female; Hormone Replacement Therapy; Humans; Incidence; Male; Prevalence; Quality of Life; Sex Factors
PubMed: 31321757
DOI: 10.1007/s40618-019-01079-6 -
International Journal of General... 2023We aim to overview Addison's disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English... (Review)
Review
We aim to overview Addison's disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English between January 2022 and December 2022 (including online ahead of print versions) in PubMed-indexed journals. We included original studies in living humans regardless of the level of statistical significance starting from the key search terms "Addison's disease" or "primary adrenal insufficiency" in title or abstract. We excluded articles with secondary adrenal insufficiency. Briefly, 199 and 355 papers, respectively were identified; we manually checked each of them, excluded the duplicates, and then selected 129 based on their clinical relevance in order to address our 1-year analysis. We organized the data in different subsections covering all published aspects on the subject of AD. To our knowledge, this is the largest AD retrospective from 2022 on published data. A massive role of genetic diagnosis especially in pediatric cases is highlighted; the importance of both pediatric and adult awareness remains since unusual presentations continue to be described. COVID-19 infection is a strong player amid this third year of pandemic although we still not do have large cohorts in this particular matter as seen, for instance, in thyroid anomalies. In our opinion, the most important topic for research is immune checkpoint inhibitors, which cause a large panel of endocrine side effects, AD being one of them.
PubMed: 37287503
DOI: 10.2147/IJGM.S390793 -
Best Practice & Research. Clinical... Jan 2020Primary adrenal insufficiency (PAI) occurs in 1/5000-1/7000 individuals in the general population. Autoimmune Addison's disease (AAD) is the major cause of PAI and is a... (Review)
Review
Primary adrenal insufficiency (PAI) occurs in 1/5000-1/7000 individuals in the general population. Autoimmune Addison's disease (AAD) is the major cause of PAI and is a major component of autoimmune polyendocrine syndrome type 1 (APS1) and type 2 (APS2). Presence of 21-hydroxylase autoantibodies (21OHAb) identifies subjects with ongoing clinical or pre-clinical adrenal autoimmunity. AAD requires life-long substitutive therapy with two-three daily doses of hydrocortisone (HC) (15-25 mg/day) or one daily dose of dual-release HC and with fludrocortisone (0.5-2.0 mg/day). The lowest possible HC dose must be identified according to clinical and biochemical parameters to minimize long-term complications that include osteoporosis and cardiovascular and metabolic alterations. Women with AAD have lower fertility and parity as compared to age-matched healthy controls. Patients must be educated to double-triple HC dose in the case of fever or infections and to switch to parenteral HC in the case of vomiting, diarrhoea or acute hypotension.
Topics: Addison Disease; Adrenal Insufficiency; Adult; Autoantibodies; Autoimmune Diseases; Autoimmunity; Female; Fludrocortisone; Humans; Hydrocortisone; Male; Pregnancy; Risk Factors; Steroid 21-Hydroxylase
PubMed: 32063488
DOI: 10.1016/j.beem.2020.101379 -
Molecules (Basel, Switzerland) Jun 2023Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients' physical appearance,... (Review)
Review
Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients' physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, 4 marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.
Topics: Humans; Skin Pigmentation; Melanins; Hyperpigmentation; Skin; Monophenol Monooxygenase
PubMed: 37375394
DOI: 10.3390/molecules28124839 -
The Veterinary Clinics of North... Jan 2023Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward,... (Review)
Review
Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward, hypothyroidism and naturally occurring Cushing's syndrome (NOCS) are more complicated. In a patient with compatible clinical signs, a single increased tT is enough to confirm hyperthyroidism, but a low tT alone is never enough to confirm hypothyroidism. A flatline result (post-stimulation cortisol <2 ug/dL) on an ACTH stimulation test (ACTHst) confirms hypoadrenocorticism, but not all dogs with NOCS have increased ACTHst results. This article explains which diagnostics should be pursued for these endocrinopathies, and how to interpret them.
Topics: Dogs; Animals; Adrenocorticotropic Hormone; Adrenal Insufficiency; Cushing Syndrome; Clinical Laboratory Techniques; Hyperthyroidism; Hypothyroidism; Dog Diseases
PubMed: 36270846
DOI: 10.1016/j.cvsm.2022.08.005 -
Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.International Journal of Molecular... Mar 2021Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40... (Review)
Review
Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4-30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave's disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto's type thyroid antibodies and has a prevalence of 10-40%. 21OH-Antibodies in Addison's disease (AD) can develop in association to APS-2.
Topics: Amenorrhea; Autoantibodies; Autoimmune Diseases; Female; Hashimoto Disease; Humans; Menopause, Premature; Ovary; Polyendocrinopathies, Autoimmune; Primary Ovarian Insufficiency
PubMed: 33807517
DOI: 10.3390/ijms22052594 -
Emergency Medicine Clinics of North... Nov 2023The adrenal glands drive physiologic homeostasis, with dysregulation in any direction causing multisystem dysfunction. Adrenal excess states include hyperaldosteronism... (Review)
Review
The adrenal glands drive physiologic homeostasis, with dysregulation in any direction causing multisystem dysfunction. Adrenal excess states include hyperaldosteronism which manifests with refractory hypertension and electrolyte abnormalities including hypernatremia and hypokalemia. Paragangliomas including pheochromocytoma can cause multisystem end-organ dysfunction due to catecholaminergic storm, which require rapid blood pressure control with phentolamine and identification of lesions amenable to surgical resection. Adrenal insufficiency states in contrast can result in hypotension and decompensation refractory to vasopressor administration, requiring adrenal supplementation via hydrocortisone.
Topics: Humans; Emergencies; Hyperaldosteronism; Hydrocortisone; Hypertension; Hypotension
PubMed: 37758424
DOI: 10.1016/j.emc.2023.06.006 -
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 -
Medicina Clinica Sep 2021Pluriglandular autoimmune syndrome (APS) can affect multiple endocrine glands and is associated with other autoimmune diseases. APS type 1 presents with... (Review)
Review
Pluriglandular autoimmune syndrome (APS) can affect multiple endocrine glands and is associated with other autoimmune diseases. APS type 1 presents with hypoparathyroidism, mucocutaneous candidiasis and Addison's disease. It is caused by AutoImmune Regulator (AIRE) gene mutation. The diagnosis includes clinical manifestations in addition to AIRE gene sequencing. SPA type 2 presents with Addison's disease, type 1 diabetes, or autoimmune thyroid disease. Multiple genes have been implicated, including those of the class II major histocompatibility complex. SPA type 3 is characterized by autoimmune thyroid disease and other autoimmune disease, excluding Addison's disease and hypoparathyroidism, 4 genes have been implicated and confer susceptibility. The diagnosis of APS type 2 and type 3 includes clinical manifestations, nevertheless, the determination of autoantibodies can be useful to predict the risk of disease manifestation and to confirm the autoimmune disease in some cases.
Topics: Addison Disease; Autoantibodies; Diabetes Mellitus, Type 1; Humans; Hypoparathyroidism; Polyendocrinopathies, Autoimmune
PubMed: 33958142
DOI: 10.1016/j.medcli.2021.02.004