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The aim of this narrative review was to discuss manifestations of endocrine disease other than diabetic foot in the lower extremities. Acromegaly, Addison's disease, Cushing's syndrome, hypo- and hyperthyroidism, hypo- and hyperparathyroidism, autoimmune polyglandular syndrome, hypopituitarism, and glucagonoma are among the endocrine diseases that may present with clinical manifestations in the lower extremities. Clinical signs vary depending on the underlying condition. Clinical suspicion is necessary for early diagnosis. Treatment of the underlying endocrine disease usually results in improvement of lower-extremity manifestations., Competing Interests: Conflicts of interestKleoniki I. Athanasiadou, Christothea A. Tsiridis, and Ioanna A. Paschou have no conflict of interest to declare. Stavroula A. Paschou has participated in clinical trials sponsored by Novo Nordisk, Sanofi, and Eli Lilly, and has received honoraria for advisory board membership or lectures from Novo Nordisk, Sanofi, Bausch Health, and Abbott. Nikolaos Papanas has been an advisory board member of TrigoCare International, Abbott, AstraZeneca, Elpen, MSD, Novartis, Novo Nordisk, Sanofi-Aventis and Takeda; has participated in sponsored studies by Eli Lilly, MSD, Novo Nordisk, Novartis and Sanofi-Aventis; received honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elpen, Galenica, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda and Vianex; and attended conferences sponsored by TrigoCare International, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Pfizer and Sanofi-Aventis. Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Practical Relevance: Addison's disease is a very rare condition in cats, with only approximately 40 cases documented in the past 40 years since it was first described in 1983., Clinical Challenges: While canine hypoadrenocorticism is a well-recognised disorder with clear diagnostic and treatment guidelines, feline hypoadrenocorticism remains a challenge because of its rarity and waxing and waning clinical signs. Furthermore, empirical treatment with corticosteroids, resulting in clinical improvement, contributes to delays in achieving the diagnosis and initiating treatment. Feline hypoadrenocorticism is diagnosed with an adrenocorticotropic hormone (ACTH) stimulation test; a low resting cortisol concentration with an inadequate or absent response to synthetic ACTH is diagnostic. Various ACTH stimulation-testing protocols are reported in published cases, with the majority using three time-limited blood samples. This can be limiting clinically, depending on cats' clinical presentation and behaviour at the veterinary practice and tolerance for procedures. Long-term treatment, similar to canine hypoadrenocorticism, consists of oral corticosteroids, with several formulations licensed in the UK, and mineralocorticoids (desoxycorticosterone pivalate), of which the only available formulation (Zycortal; Dechra) is licensed for dogs and its safety has not been assessed in cats., Global Importance: Feline hypoadrenocorticism occurs worldwide. Although no breed, sex or age association has been reported, cats aged <6 years are overrepresented., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Adrenal tuberculosis remains the main cause of primary adrenal insufficiency (PAI) in tuberculosis (TB)-prevalent regions. This case report details the presentation of PAI due to adrenal TB, where the etiological diagnosis involves Abdominal Computed Tomography (CT)., Case Report: A 37-year-old Peruvian woman with a history of TB contact displayed symptoms of adrenal insufficiency. PAI diagnosis was established, and CT imaging unveiled bilateral adrenal enlargement with calcifications. Treatment with prednisone and anti-TB therapy led to symptomatic improvement. Unfortunately, she succumbed to pneumonia after ten months of follow-up., Discussion: Adrenal TB must be considered in endemic regions and in the presence of a TB history. CT serves as a valuable diagnostic tool, particularly in settings with limited resources, revealing adrenal enlargement and calcifications., Conclusion: In patients with PAI, epidemiological history of TB, and when a rapid biopsy is not feasible, CT proves to be a valuable diagnostic method., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign., Case Report: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies., Conclusions: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3]., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hyperkalemic paralysis in the setting of acute renal failure can lead to a missed or delayed diagnosis of adrenal insufficiency as the raised potassium can be attributed to the renal failure. Acute kidney injury as the presenting manifestation in an adrenal crisis due to Addison's disease has been rarely reported in the literature. Here, we present the case of a young 37-year-old male who came with hyperkalemic paralysis and acute renal failure needing emergent hemodialysis. He had no past medical history and no medication history. His hyponatremia, hypotension, and hyperkalemia pointed to a picture of adrenal insufficiency confirmed by undetectable serum cortisol, elevated ACTH, renin, and low aldosterone levels and imaging. Replacement steroid therapy was given, and the patient made a steady recovery. He was advised on the importance of compliance to treatment at discharge to prevent another crisis event. Acute renal failure with hyperkalemia as a presenting manifestation of Addison's disease can be very misleading. It is especially important to be vigilant of adrenal insufficiency in such patients as the hyperkalemia is resistant to standard therapy of insulin dextrose and can precipitate fatal arrhythmia if treatment is delayed. [ABSTRACT FROM AUTHOR]

Background: Adrenal tuberculosis is difficult to diagnose due to non-specific symptom. Unexpected death due to adrenal insufficiency after trauma surgery is rare. Case presentation: A 45-year-old man, who was admitted to hospital because of trauma to the right hand, died unexpectedly on the 13th day after replantation of amputated fingers. He was diagnosed with brain edema and diluted hyponatremia. Autopsy and histopathologic examination revealed severe brain edema combined with cerebellar tonsillar hernia, extensive destruction of adrenal gland caused by bilateral adrenal tuberculosis and right lung invasive pulmonary tuberculosis. Conclusions: Trauma and pulmonary tuberculosis complicated with adrenal tuberculosis induced the adrenal crisis, which eventually lead to severe cerebral edema and hernia, and finally death from respiratory and circulatory failure. This autopsy and histopathologic examination suggested a possible pathophysiologic mechanism of sudden death due to diluted hyponatremia after trauma surgery. [ABSTRACT FROM AUTHOR]

Antigen presentation by B cells carrying two MHC haplotypes can bridge the MHC barrier between two compartments of B cells that do not share MHC haplotypes, by communicating with two separate pools of MHC-restricted T cells. Furthermore, conventional T cells are the only responding cells in early life, whereas in the 7-year-olds and adults, the bulk of the IFN- response comes from T cells, MAIT cells and NK cells. Next, we will map intrinsic determinants via single cell analysis, and further investigate how the development of T1D, and populations of cell-reactive CD8+ T cells differs between disease status, and disease stages. 63 Molecular requirements for antigen-driven B cell activation A. Ferapontov SP 1,2 sp ; M. Omer SP 2,3 sp ; I. Baudrexel SP 2,4 sp ; J. Nielsen SP 2,3 sp ; D. Dupont SP 2,3 sp ; K. Juul-Madsen SP 1 sp , S. Thiel SP 1,2 sp ; T. Vorup-Jensen SP 1 sp ; R. Jungmann SP 2,4 sp ; J. Kjems SP 2,3 sp ; S. Degn SP 1,2 sp I SP 1 sp Aarhus University, Aarhus C, Denmark, SP 2 sp Center for Cellular Signal Patterns (CellPAT), Aarhus C, Denmark, SP 3 sp Interdisciplinary Nanoscience Center (iNANO), Aarhus C, Denmark, SP 4 sp Max Planck Institute of Biochemistry, Martinsried, Germany i B cells play a vital role in the adaptive immune response by generating antigen specific antibodies. Thus, antibody-coated PLTs can activate NK cells leading to their elimination by ADCC, suggesting that NK cells may be involved in the in vivo clearance of platelets in the presence of antibodies against antigens expressed on PLT 81 Convalescent COVID-19 patients show immuno-dominant cross reactivity against Common Cold Coro... J. [Extracted from the article]

Type 1 autoimmune polyglandular syndrome (APS1) is a rare hereditary disease affecting nearly 600 patients worldwide. The first of its cardinal manifestations, chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison's disease, presents in childhood. Additional nonclassical landmarks of APS1 continue to develop as late as the fifth decade of life. Two thirds of patients develop the full triad before 25 years of age. Only 20% of patients develop the entire triad simultaneously. Addison's disease is rarely reported as the first manifestation. According to APS1 classifications, restricted criteria for a single cardinal component, although elements of suspicion are not sufficient to diagnose APS1. This case report is peculiar as hypoadrenalism was the first and only manifestation of APS1 for nearly 3 decades since its diagnosis. Theoretically, exceptions from the protocol of APS1 diagnostic criteria would be recognized as acceptable for diagnosis in the future, when similar case reports of only 1 component of APS1 appear. [ABSTRACT FROM AUTHOR]

Background: Most dogs with primary hypoadrenocorticism (HA) have a mineralocorticoid deficiency, which decreases renal tubular sodium reabsorption and potassium excretion. Limited information is available concerning the clinical value of measuring urine electrolytes to aid in an HA diagnosis. Objectives: We aimed to evaluate the diagnostic utility of urine electrolyte measurements in dogs with HA. Methods: Urine sodium and potassium concentrations were measured in 89 dogs, including 39 dogs with HA and 50 controls with nonadrenal illness. Fractional excretions of sodium (FENa) and potassium (FEK) were also calculated. Urine electrolytes and fractional excretion values were compared between the groups. Sensitivities and specificities were determined for various cut‐points. Results: The median urine sodium to potassium (Na:K) ratio was twofold greater (P <.001), and median FENa was fourfold greater (P <.001) in HA dogs as compared with controls. However, no cut‐point for any variable with >90% sensitivity or specificity provided a corresponding specificity or sensitivity of >50%. When only dogs with abnormal serum or plasma electrolytes were included in the analyses, absolute urine electrolyte concentrations and FENa were not different between study populations (P >.05 for all comparisons), but the FEK was increased (P =.005) and the urine potassium:creatinine ratio was decreased (P <.001) in the control dogs compared with the dogs with HA. Conclusions: Urine electrolyte concentrations and fractional excretions are altered in dogs with HA. However, substantial overlap exists with control dogs with nonadrenal illness. Therefore, these values are unlikely to have diagnostic utility for dogs with HA. [ABSTRACT FROM AUTHOR]

Objectives: CD8+ T cells targeting 21-hydroxylase (21OH) are presumed to play a central role in the destruction of adrenocortical cells in autoimmune Addison's disease (AAD). Earlier reports have suggested two immunodominant CD8+ T cell epitopes within 21OH: LLNATIAEV (21OH342-350), restricted by HLA-A2, and EPLARLEL (21OH431-438), restricted by HLA-B8. We aimed to characterize polyclonal CD8+ T cell responses to the proposed epitopes in a larger patient cohort with AAD. Methods: Recombinant fluorescent HLA-peptide multimer reagents were used to quantify antigen-specific CD8+ T cells by flow cytometry. Interferon-gamma (IFNγ) Elispot and biochemical assays were used to functionally investigate the 21OH-specific T cells, and to map the exactly defined epitopes of 21OH. Results: We found a significantly higher frequency of HLA-A2 restricted LLNATIAEV-specific cells in patients with AAD than in controls. These cells could also be expanded in vitro in an antigen specific manner and displayed a robust antigen-specific IFNγ production. In contrast, only negligible frequencies of EPLARLEL-specific T cells were detected in both patients and controls with limited IFNγ response. However, significant IFNγ production was observed in response to a longer peptide encompassing EPLARLEL, 21OH430-447, suggesting alternative dominant epitopes. Accordingly, we discovered that the slightly offset ARLELFVVL (21OH434-442) peptide is a novel dominant epitope restricted by HLA-C7 and not by HLA-B8 as initially postulated. Conclusion: We have identified two dominant 21OH epitopes targeted by CD8+ T cells in AAD, restricted by HLA-A2 and HLA-C7, respectively. To our knowledge, this is the first HLA-C7 restricted epitope described for an autoimmune disease. [ABSTRACT FROM AUTHOR]

Primary adrenal insufficiency, also known as Addison's disease, is a rare but potentially fatal condition resulting from the failure of the adrenal cortex to produce glucocorticoid and/or mineralocorticoid hormones. Unfortunately, the clinical manifestation of primary adrenal insufficiency is not specific and often progresses insidiously, resulting in late diagnosis, or in severe cases, life-threatening circulatory collapse. Adrenal insufficiency should be considered in patients with unexplained vascular collapse. We report the case of a woman who presented to the emergency ward with unexplainable shock that was later diagnosed as adrenal crisis due to Addison's disease. The presence of hyperpigmentation in patients with rapid progression of adrenal insufficiency suggests the diagnosis of Addison's disease presenting with adrenal crisis. [ABSTRACT FROM AUTHOR]

We aim to address incomplete procedures of adrenalectomy for pheochromocytoma (PHEO) on a bases of a mini-review. Dopamine, adrenaline and noradrenaline – secretor tumors are rare in general population, representing a neuroendocrine neoplasia with a strong genetic driving force and uncertain profile concerning a malignant behavior which may be less or more predicted based on initial post-operative report. There is no linear correlation with the post-operative recurrence in terms of clinical presentation, timing and prognostic. The first laparoscopic – based PHEO removal was done in 1992; and since then, the open procedure was replaced in majority of cases by the new gold standard – laparoscopic adrenalectomy; a current conversion rate is of 5%; alpha and beta - blockade is mandatory for preoperative management since an adrenergic crisis might be triggered by higher intraabdominal pressure during laparoscopy; bilateral PHEO may be addressed through one time procedure; minimally invasive technique is done trans-peritoneal or retroperitoneal; robotic – assisted laparoscopic procedure is the next logical step from traditional laparoscopy; in children, minimally invasive procedure is less likely to be used as in adults. Partial adrenalectomy (in terms of cortical - sparing technique) should be rarely performed for unilateral PHEO; its potential utility is for cases with non-feasible total removal due to tumor anatomy (like advanced local disease) or bilateral adrenal involvement in hereditary syndromes (like MEN 2A, VHL), especially in children and young adults to overcome the need of life long glucocorticoid replacement due to chronic adrenal insufficiency. A meta-analysis focusing on recurrence after total adrenalectomy revealed a 3% ratio after 2 years in PHEO. The percent for partial procedure is more than 10% depending on study. In conclusion, a particular aspect in PHEO management is the recurrence after an adrenalectomy, typically after a partial procedure. Unless bilateral involvement or a clear diagnostic of a hereditary syndrome involving bilateral PHEO, partial adrenalectomy should be limited. [ABSTRACT FROM AUTHOR]

The aim of our study was to examine whether slow or rapid cryopreservation of adrenal xenografts affected xenotransplant outcome. Adrenal xenografts were got from newborn piglets (<24 h after birth). Receptor rats were randomly divided into four groups: a bilateral adrenalectomy group, fresh xenotransplantation group, rapid cryopreservation xenotransplantation group, and a slow cryopreservation xenotransplantation group. 30 days after xenotransplantation, the survival rates of rats in the fresh xenotransplantation group, rapid cryopreservation xenotransplantation group and slow cryopreservation xenotransplantation group were 80 %, 60 % and 60 %, respectively, which were significantly higher than 40 % of the bilateral adrenalectomy group. In addition, the survival rate of rats in the slow cryopreservation group was consistently significantly higher than that in the rapid cryopreservation group at 29 days after xenotransplantation. Morphological observation showed that there were a few medulla cells existed in the adrenal glands in the slow cryopreservation group after 30 days of xenotransplantation, but no medulla cells were found in the rapid cryopreservation group. The plasma cortisol level of rats in the fresh xenotransplantation group and the slow xenotransplantation group 30 days after xenotransplantation was significantly higher than that of the rapid cryopreservation group and bilateral adrenalectomy group (P < 0.05). The levels of liver glycogen and cholesterol in the xenotransplantation rats were increased relative to those of the bilateral adrenalectomy rats, and close to normal level. In conclusion, compared with rapidly frozen preserved grafts, slowly frozen preserved grafts not only ensure the structural integrity of adrenal tissues, but also have corresponding physiological functions, which provid a basic research opportunities for the preservation of xenografts and the treatment of adrenal corticosteroid deficiency. Moreover, these findings can provide evidence for xenotransplantation in the treatment of Addison's disease (adrenal cortex hormone deficiency). [ABSTRACT FROM AUTHOR]

BackgroundSebaceous adenitis (SA) and Addison's disease (AD) increased rapidly in incidence among Standard Poodles after the mid-twentieth century. Previous attempts to identify specific genetic causes using genome wide association studies and interrogation of the dog leukocyte antigen (DLA) region have been non-productive. However, such studies led us to hypothesize that positive selection for desired phenotypic traits that arose in the mid-twentieth century led to intense inbreeding and the inadvertent amplification of AD and SA associated traits.ResultsThis hypothesis was tested with genetic studies of 761 Standard, Miniature, and Miniature/Standard Poodle crosses from the USA, Canada and Europe, coupled with extensive pedigree analysis of thousands more dogs. Genome-wide diversity across the world-wide population was measured using a panel of 33 short tandem repeat (STR) loci. Allele frequency data were also used to determine the internal relatedness of individual dogs within the population as a whole. Assays based on linkage between STR genomic loci and DLA genes were used to identify class I and II haplotypes and disease associations. Genetic diversity statistics based on genomic STR markers indicated that Standard Poodles from North America and Europe were closely related and reasonably diverse across the breed. However, genetic diversity statistics, internal relatedness, principal coordinate analysis, and DLA haplotype frequencies showed a marked imbalance with 30 % of the diversity in 70 % of the dogs. Standard Poodles with SA and AD were strongly linked to this inbred population, with dogs suffering with SA being the most inbred. No single strong association was found between STR defined DLA class I or II haplotypes and SA or AD in the breed as a whole, although certain haplotypes present in a minority of the population appeared to confer moderate degrees of risk or protection against either or both diseases. Dogs possessing minor DLA class I haplotypes were half as likely to develop SA or AD as dogs with common haplotypes. Miniature/Standard Poodle crosses being used for outcrossing were more genetically diverse than Standard Poodles and genetically distinguishable across the genome and in the DLA class I and II region.ConclusionsAncestral genetic polymorphisms responsible for SA and AD entered Standard Poodles through separate lineages, AD earlier and SA later, and were increasingly fixed by a period of close linebreeding that was related to popular bloodlines from the mid-twentieth century. This event has become known as the midcentury bottleneck or MCB. Sustained positive selection resulted in a marked imbalance in genetic diversity across the genome and in the DLA class I and II region. Both SA and AD were concentrated among the most inbred dogs, with genetic outliers being relatively disease free. No specific genetic markers other than those reflecting the degree of inbreeding were consistently associated with either disease. Standard Poodles as a whole remain genetically diverse, but steps should be taken to rebalance diversity using genetic outliers and if necessary, outcrosses to phenotypically similar but genetically distinct breeds.

ObjectivesCD8+ T cells targeting 21-hydroxylase (21OH) are presumed to play a central role in the destruction of adrenocortical cells in autoimmune Addison’s disease (AAD). Earlier reports have suggested two immunodominant CD8+ T cell epitopes within 21OH: LLNATIAEV (21OH342-350), restricted by HLA-A2, and EPLARLEL (21OH431-438), restricted by HLA-B8. We aimed to characterize polyclonal CD8+ T cell responses to the proposed epitopes in a larger patient cohort with AAD.MethodsRecombinant fluorescent HLA-peptide multimer reagents were used to quantify antigen-specific CD8+ T cells by flow cytometry. Interferon-gamma (IFNγ) Elispot and biochemical assays were used to functionally investigate the 21OH-specific T cells, and to map the exactly defined epitopes of 21OH.ResultsWe found a significantly higher frequency of HLA-A2 restricted LLNATIAEV-specific cells in patients with AAD than in controls. These cells could also be expanded in vitro in an antigen specific manner and displayed a robust antigen-specific IFNγ production. In contrast, only negligible frequencies of EPLARLEL-specific T cells were detected in both patients and controls with limited IFNγ response. However, significant IFNγ production was observed in response to a longer peptide encompassing EPLARLEL, 21OH430-447, suggesting alternative dominant epitopes. Accordingly, we discovered that the slightly offset ARLELFVVL (21OH434-442) peptide is a novel dominant epitope restricted by HLA-C7 and not by HLA-B8 as initially postulated.ConclusionWe have identified two dominant 21OH epitopes targeted by CD8+ T cells in AAD, restricted by HLA-A2 and HLA-C7, respectively. To our knowledge, this is the first HLA-C7 restricted epitope described for an autoimmune disease.

Addison's disease is primary adrenal insufficiency which is most commonly due to an autoimmune disease. Patients usually presents with fatigue, anorexia, gastrointestinal complaints, salt craving, and orthostatic hypotension. Rare manifestations during presentation can result in diagnostic dilemma. A 53-year-old male presented with cerebellar ataxia and bipolar disorder secondary to Addison's disease (due to tuberculous adrenalitis) which improved following treatment with steroids. We describe a patient with Addison's disease who presented with two rare manifestations which to our knowledge is the first such report.

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.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison's disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves' disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves' disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea. [ABSTRACT FROM AUTHOR]

Context: Autoimmune diseases affect ~8% of the population. Type 1 diabetes mellitus (T1DM) is linked to other autoimmune diseases (AIDs), such as autoimmune thyroid disease or Addison's disease (AD), that may impact diabetes therapy and outcome.Objective: To analyze demographic and clinical characteristics of other AIDs in T1DM from a large standardized registry, the Prospective Diabetes Follow-up Registry (DPV).Methods: We searched the registry for T1DM with the additional diagnosis of Hashimoto's thyroiditis (HT), Graves' disease (GD), and/or AD. T1DM with other AIDs (n = 6166, 5.4%) were compared with isolated T1DM (n = 107 457). For group comparisons, we used multivariable regression models with age, sex, diabetes duration, migration background, and type of insulin regimen as basic adjustments (microvascular endpoints: additionally adjusted for glycated hemoglobin).Results: Patients with additional AIDs were more often female (54.7 vs 32.0%, P < .001) and had a longer diabetes duration (7.9 [4.2-12.5] vs 6.7 [2.7-12.9] years, P < .001). After adjustment, daily insulin dosage was higher in AD and HT than in isolated T1DM (0.858 ± 0.032 and 0.813 ± 0.005 vs 0.793 ± 0.001 IU/kg per day). Retinopathy was less common in HT (1.5%), whereas it was more frequent in GD (3.1%) than in isolated T1DM (1.8%). In both GD and HT, microalbuminuria occurred less often (10.6% and 14.3% vs 15.5%) and neuropathy (2.1% and 1.8% vs 0.8%) was more common than in isolated T1DM. All P < .05.Conclusion: T1DM with additional AIDs show heterogeneous differences compared with isolated T1DM. T1DM plus AD or HT requires more insulin. Further, the rate of neuropathy is higher in HT or GD, whereas the rate of microalbuminuria is lower. [ABSTRACT FROM AUTHOR]

Autoimmune polyendocrine syndrome type I (APS-1) is a monogenic model disorder of organ-specific autoimmunity caused by mutations in the Autoimmune regulator (AIRE) gene. AIRE facilitates the expression of organ-specific transcripts in the thymus, which is essential for efficient removal of dangerous self-reacting T cells and for inducing regulatory T cells (Tregs). Although reduced numbers and function of Tregs have been reported in APS-I patients, the impact of AIRE deficiency on gene expression in these cells is unknown. Here, we report for the first time on global transcriptional patterns of isolated Tregs from APS-1 patients compared to healthy subjects. Overall, we found few differences between the groups, although deviant expression was observed for the genes TMEM39B, SKIDA1, TLN2, GPR15, FASN, BCAR1, HLA-DQA1, HLA-DQB1, HLA-DRA, GPSM3 and AKR1C3. Of significant interest, the consistent downregulation of GPR15 may indicate failure of Treg gut homing which could be of relevance for the gastrointestinal manifestations commonly seen in APS-1. Upregulated FASN expression in APS-1 Tregs points to increased metabolic activity suggesting a putative link to faulty Treg function. Functional studies are needed to determine the significance of these findings for the immunopathogenesis of APS-1 and for Treg immunobiology in general. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with the monogenic immune dysregulatory syndrome autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene, uniformly carry neutralizing autoantibodies directed against type-I interferons (IFNs) and many develop autoimmune pneumonitis, both of which place them at high risk for life-threatening COVID-19 pneumonia. Bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target the SARS-CoV-2 spike protein and block entry of SARS-CoV-2 in host cells. The use of bamlanivimab and etesevimab early during infection was associated with reduced COVID-19–associated hospitalization and death in patients at high risk for progressing to severe disease, which led the US Food and Drug Administration to issue an emergency use authorization for their administration in non-hypoxemic, non-hospitalized high-risk patients. However, the safety and efficacy of these mAbs has not been evaluated in APECED patients. We enrolled two siblings with APECED on an IRB-approved protocol (NCT01386437) and admitted them prophylactically at the NIH Clinical Center for evaluation of mild-to-moderate COVID-19. We assessed the safety and clinical effects of early treatment with bamlanivimab and etesevimab. The administration of bamlanivimab and etesevimab was well tolerated and was associated with amelioration of COVID-19 symptoms and prevention of invasive ventilatory support, admission to the intensive care, and death in both patients without affecting the production of antibodies to the nucleocapsid protein of SARS-CoV-2. If given early in the course of COVID-19 infection, bamlanivimab and etesevimab may be beneficial in APECED and other high-risk patients with neutralizing autoantibodies directed against type-I IFNs. [ABSTRACT FROM AUTHOR]

Providers should remain vigilant of autoimmune polyglandular syndrome type II in the context of persistent low blood sugar in type I diabetes. Correction of adrenal insufficiency is key for regulation of blood sugar and thyroid function. [ABSTRACT FROM AUTHOR]

Antidepressants have a wide range of molecular mechanisms of action. Antidepressants are amphiphilic chemicals, which allow them to easily pass across the cell membrane and influence molecules on the outer and inner membrane surfaces, as well as cytoplasmic and nuclear molecules, Depressed persons may lose interest in once-pleasurable activities or experience cognitive problems (e.g., difficulty concentrating, remembering details, making decisions). They may think about or attempt suicide. Their weight might fluctuate considerably. Insomnia, excessive sleeping, sleep pattern changes (e.g., waking up in the middle of the night or early in the morning and being unable to fall asleep again), weariness, lack of energy, and aches, pains, or digestive disorders that are resistant to therapy may be present. Depressed mood is a normal reaction to some life experiences, a sign of many medical diseases (for example, Addison's disease, hypothyroidism), and a hallmark of several mental illnesses. [ABSTRACT FROM AUTHOR]

Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison's disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison's disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison's disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data. [ABSTRACT FROM AUTHOR]

Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete. [ABSTRACT FROM AUTHOR]

Background: Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods: A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results: A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion: Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency. [ABSTRACT FROM AUTHOR]

Background: Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital.Results: In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison's disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1.Conclusion: We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1. [ABSTRACT FROM AUTHOR]

Background: Schmidt's syndrome (SS) is a rare endocrine disorder (14-20:1000000), which consists of autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD), and usually occurs in young adults. Here, we report a unique case of late-onset SS manifesting initially with isolated severe hyponatremia and present the hazardous outcomes of preliminary misdiagnosis. Case Presentation: A 78-year-old female presented to the emergency department with a two-day history of diarrhea, emesis and disturbances in consciousness. She also reported general fatigue and increasing weakness in the last month. Urgent laboratory findings revealed isolated severe hyponatremia (serum sodium=108 mmol/l) and initial treatment with active sodium infusions was started, although with no improvement in the patient's neurological status after 5 days (serum sodium=127 mmol/l). Meanwhile, the patient developed recurring episodes of hypoglycemia and symptoms portending adrenal crisis (blood pressure=105/58 mmHg, heart rate=96 bpm, severe whole-body muscle pain, two loose stools), which required immediate i.e. hydrocortisone treatment. Reduced blood cortisol, elevated adrenocorticotropic hormone (ACTH) and atrophic morphology of the adrenal glands in computed tomography imaging contributed to the final diagnosis of aAD and SS consequently, since the patient had a past medical history of AIT. Conclusion: Isolated severe hyponatremia should not be underestimated as the first sign of aAD. Appropriate cause-specific treatment is crucial in managing hyponatremia. [ABSTRACT FROM AUTHOR]

Background: Schmidt's syndrome (SS) is a rare endocrine disorder (14-20:1000000), which consists of autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD), and usually occurs in young adults. Here, we report a unique case of late-onset SS manifesting initially with isolated severe hyponatremia and present the hazardous outcomes of preliminary misdiagnosis. Case presentation: A 78-year-old female presented to the emergency department with a two-day history of diarrhea, emesis and disturbances in consciousness. She also reported general fatigue and increasing weakness in the last month. Urgent laboratory findings revealed isolated severe hyponatremia (serum sodium=108 mmol/l) and initial treatment with active sodium infusions was started, although with no improvement in the patient's neurological status after 5 days (serum sodium=127 mmol/l). Meanwhile, the patient developed recurring episodes of hypoglycemia and symptoms portending adrenal crisis (blood pressure=105/58 mmHg, heart rate=96 bpm, severe whole-body muscle pain, two loose stools), which required immediate i.e. hydrocortisone treatment. Reduced blood cortisol, elevated adrenocorticotropic hormone (ACTH) and atrophic morphology of the adrenal glands in computed tomography imaging contributed to the final diagnosis of aAD and SS consequently, since the patient had a past medical history of AIT. Conclusion: Isolated severe hyponatremia should not be underestimated as the first sign of aAD. Appropriate cause-specific treatment is crucial in managing hyponatremia. [ABSTRACT FROM AUTHOR]

Background: Desoxycorticosterone pivalate (DOCP) is a commonly used mineralocorticoid replacement for dogs with primary hypoadrenocorticism (HA), but manufacturer‐recommended dosing protocols can be cost‐prohibitive. Recent reports also have raised concerns that label dose protocols could be excessive. Objective: To investigate the relative efficacy and adverse effects of 2 DOCP dosages in dogs with primary glucocorticoid and mineralocorticoid deficient HA. Animals: Thirty‐seven dogs, including 19 test population dogs and 18 controls. Methods: Randomized controlled double‐blinded clinical trial. Dogs with newly diagnosed primary HA were assigned to standard (2.2 mg/kg q30d, control population) or low‐dose (1.1 mg/kg q30d, test population) DOCP treatment. Clinical and laboratory variables were assessed 10 to 14 days and approximately 30 days after each DOCP treatment for 90 days. Results: Mean serum sodium to potassium ratios at reevaluations were ≥32 in both populations throughout the study. No dog developed electrolyte abnormalities warranting medical treatment, although hypokalemia occurred on at least 1 occasion in 9 controls and 6 test population dogs. Urine specific gravities (median, interquartile range) were lower in control dogs (1.022, 1.016‐1.029) as compared to test population dogs (1.033, 1.023‐1.039; P =.006). Plasma renin activity was overly suppressed on 84 of 104 (80.8%) assessments in control dogs whereas increased renin activity occurred on 23 of 112 (20.5%) assessments in test population dogs. Conclusions and Clinical Importance: Low‐dose DOCP protocols appear to be safe and effective for treatment of HA in most dogs. Standard‐dose protocols are more likely to result in biochemical evidence of overtreatment. [ABSTRACT FROM AUTHOR]

We report on a 48-year-old patient with X-linked adrenoleukodystrophy with slowly progressive leg-accentuated spastic paraparesis, vegetative dysfunction with bladder and sexual dysfunction, and primary adrenal insufficiency. The diagnosis of adrenomyeloneuropathy, the adult form of adrenoleukodystrophy, and Addison's disease was made at the age of 20 by evidence of an increased concentration of long-chain fatty acids in the plasma. The therapy is symptom-oriented. [ABSTRACT FROM AUTHOR]

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Context: Primary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison's disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied.Objective: To assess the prevalence of POI in a large cohort of women with AAD and describe clinical, immunological, and genetic characteristics.Methods: An observational population-based cohort study of the Norwegian National Addison Registry. The Norwegian Prescription Database was used to assess prescription of menopausal hormone replacement therapy (HRT). A total of 461 women with AAD were studied. The primary outcome measure was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism variation.Results: The prevalence of POI was 10.2% (47/461) and one-third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%).Conclusion: One in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD <40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC. [ABSTRACT FROM AUTHOR]

Context: Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations.Objective: To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population.Methods: A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis.Results: With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15-7.46]). Adrenal crisis contributed to 10% of all deaths. In the first 2 years following diagnosis, the patients' mortality rate and hospitalization from adrenal crisis were higher than in later years.Conclusion: Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality. [ABSTRACT FROM AUTHOR]

Introduction: The pituitary gland is considered as the master gland as it regulates all other major hormones. The corticotroph cells of the anterior pituitary gland secretes the adrenocorticotrophic hormone (ACTH) which initiate corticosterone production in rodents via the hypothalamic–pituitary-adrenal axis (HPA axis). The ACTH and corticosterone are frequently used as the hormonal marker for measurement of physiological stress. Disturbance in the ACTH and corticosterone hormones were observed in many modern diseases such as Addison’s disease, Cushing’s syndrome, and metabolic syndrome. The objective of this study is to identify which particular diet produces the most and least physiological stress on the Sprague Dawley rat. Methods: Thirty-five male Sprague Dawley rats were randomly grouped into five groups (n=7). They were given five different types of diets namely control, high-fat, high-protein, high-sugar, and high-starch. Tap water was supplied as drinking water. Both the diets and drinking water were supplied ad libitum. After eight weeks of treatment with the diets, the rat’s blood was collected, and their serum separated. The individual components of ACTH and corticosterone from the blood was extracted, purified, identified using the standard HPLC protocol. The two hormones were then quantified using the High-Performance Liquid Chromatography (HPLC) with photodiode array (PDA) analysis method. Results: The HPLC results revealed that a high -sugar diet promotes the highest ACTH blood level. It was also noted that both the high-fat and high-sugar diet group showed the highest peak for corticosterone. Conclusion: Consumption of high-fat and high-sugar diet for eight weeks is suggested to induce physiologic and metabolic stress in Sprague Dawley rats as evidenced by the HPA activation. [ABSTRACT FROM AUTHOR]

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO 2 , DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro , and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice. [ABSTRACT FROM AUTHOR]

• Genetic susceptibility to vitiligo links to multiple autoimmune diseases via blood metabolites. • Integrating metabolomic and genomic data unveils vitiligo's etiological links with immunological conditions. • Discoveries yield diagnostic markers and treatment targets for vitiligo and related autoimmune diseases. This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites. We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases. Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08–1.27), psoriasis (OR 1.10; 95 % CI 1.04–1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23–1.63), pernicious anemia (OR 1.23; 95 % CI 1.12–1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11–1.26), alopecia areata (OR 1.22; 95 % CI 1.10–1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12–1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated. We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: The spectrum of neuropsychiatric adverse effects of corticosteroids ranges from unspecific symptoms to structured psychotic or affective episodes. We present the case of a 30-year-old woman admitted to our hospital due to behavioral alterations, coinciding with the initiation of treatment with corticosteroid boluses as part of a chemotherapy regimen for gastric adenocarcinoma. She had a previous diagnose of Addison's disease, undergoing treatment with supplemental corticosteroids. Objectives: 1) To describe the clinical particularities of this case, focusing on the psychopathological aspects and their correlation with the corticoid treatment. 2) To review the available literature regarding the clinical characteristics and management of corticosteroid-induced psychosis, with special interest in patients with adrenal insufficiency that require long term steroid supplementation. Methods: A review of the patient's clinical history and complementary tests were carried out. Likewise, we reviewed the available literature in relation to the clinical presentation of corticosteroid-induced psychosis and its pharmacological management. Results: The patient was admitted to our hospital due to acute behavioural alterations, which temporally coincided with the 4th cycle of FOLFOX chemotherapy and corticosteroid boluses. She presented with incoherent speech, with non sequitur answers and glossolalia, as well as dysphoric affect and purposeless behavior. She presented a favorable clinical course after the initiation of treatment with antipsychotics and temporary suspension of corticosteroid treatment. Manic symptoms are the most common presentation of "corticosteroid-induced psychosis", with the key characteristic being the temporal association with the corticosteroids administration. Although the discontinuation of steroids generally results in a sudden decrease in symptoms, additional treatment with antipsychotics such as haloperidol or olanzapine might be required for a symptomatic control. In patients with adrenal insufficiency, long-term treatment with lithium or anti-seizure treatments are effective strategies in relapse prevention when a higer steroid dose is required. Conclusions: - Corticosteroid-induced psychosis is a well described clinical phenomenon, that usually presents with manic symptoms rather than psychotic experiences. - Progressive discontinuation of corticosteroid treatment usually results in complete cessation of symptoms, but additional psychopharmacological treatment might be required, especially in patients with adrenal insufficiency undergoing long-term corticosteroid treatment. - This case outlines the psychopathological richness in the presentation of corticosteroid-induced psychosis, and illustrates the challenges in the pharmacological management in patients with adrenal insufficiency. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]