Autoimmune Polyglandular Syndrome Research Articles

Cutaneous lymphoid hyperplasia in a male patient with type 3 polyglandular autoimmune syndrome - a rare association

Cutaneous lymphoid hyperplasia in a male patient with type 3 polyglandular autoimmune syndrome - a rare association

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

Update on autoimmune polyendocrine syndrome type-1 in Norway: Using longitudinal immune cell composition incorporated with clinical features

Update on autoimmune polyendocrine syndrome type-1 in Norway: Using longitudinal immune cell composition incorporated with clinical features

Addison's disease presented as a persistent hyperkaliemia in a patient with diabetic ketosis and autoimmune polyendocrine syndrome type 2 (APS-2). a case report and review of literature

Addison's disease presented as a persistent hyperkaliemia in a patient with diabetic ketosis and autoimmune polyendocrine syndrome type 2 (APS-2). a case report and review of literature

Autoimmune polyendocrinopathy type 2 associated with celiac disease: a case report

Autoimmune polyendocrinopathy type 2 associated with celiac disease: a case report

Association of latent autoimmune diabetes of adults with type 3 polyglandular autoimmune syndrome—a diagnostic challenge

Autoimmune polyendocrine syndromes (APS) encompass multiple endocrine gland insufficiencies associated with autoimmune disease. This case report underscores the importance of recognising the association between latent autoimmune diabetes of adults (LADA) and type 3 polyglandular syndrome. A 42-year-old man belonging to Rawalpindi, Pakistan, presented to the outpatient department (OPD) of Ali Medical Centre, Islamabad, in January 2023 with the complaints of extreme thirst and frequent urination. The patient reported consistently raised appetite and eating four to five meals a day along with abrupt weight loss, dry mouth, fatigue occasional dizziness, and dyspnoea. He was diagnosed with type 3 polyglandular syndrome with association of LADA. Daily administration of 10 units of glargine insulin, along with six units of rapid-acting insulin, was prescribed. The patient's HbA1c level reduced in a few months after successive follow-up. ---Continue

CD20 + T lymphocytes in isolated Hashimoto's thyroiditis and type 3 autoimmune polyendocrine syndrome: a pilot study.

CD20+ T cells represent up to 5% of circulating T lymphocytes. These cells have been shown to produce higher levels of IL-17A and IFN-γ than those of CD20-T lymphocytes. Some reports described the role of CD20+ T cells in autoimmune disorders such as multiple sclerosis and rheumatoid arthritis possibly due to their ability to produce these inflammatory cytokines. This study is aimed at describing the behavior of CD20+ T lymphocytes in the most frequent autoimmune disorder, i.e., Hashimoto's thyroiditis (HT), presenting isolated or associated to further autoaggressive disorders in a frame of poly-autoimmunity. The study group encompasses 65 HT patients: 23 presenting in isolated form (IT) and 42 with an associated non-endocrine autoimmune disorder [16 with chronic atrophic gastritis (CAG), 15 with nonsegmental vitiligo (VIT), and 11 with celiac disease (CD)]. Twenty healthy donors act as control group (HD). Chronic use of interfering drugs, severe or chronic disorders, and pregnancy and lactation were used as exclusion criteria. Whole blood samples (100µl) were stained with fluorescent-labeled antibodies (anti-CD45, anti-CD3, anti-CD19, anti-CD16, anti-CD56, anti-CD4, anti-CD8, anti-CD20). Red blood cells were then lysed by adding 1ml of hypotonic buffer, and samples were acquired on a Flow Cytometer. CD3+CD8+CD20+ T lymphocytes' percentages, were significantly higher in the whole group of autoimmune patients compared to healthy donors (p = 0.0145). Dividing HT patients based on the type of presentation of autoimmune thyroiditis, CAG group showed the highest percentage of these cells as compared to HD and CD (p = 0.0058). IT patients showed higher percentages of CD3+ CD8+CD20+ cells than those of HD patients although not reaching statistical significance. However, dividing IT group based on thyroid function, hypothyroid patients showed higher CD8+CD20+ cell percentages than those of HD and euthyroid patients (p = 0.0111). Moreover, in IT patients, these cells were negatively correlated with FT4 levels (p = 0.0171; r = -0.4921). These preliminary findings indicate that CD8+CD20+ T cells are activated in patients with autoimmune thyroiditis and may behave differently according to the presence of poly-autoimmunity and hypothyroidism.

Exploring Chronic Hypocalcemia: Insights into Autoimmune Polyglandular Syndrome Type 1-A Case Study and Literature Review.

Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions.

Autoimmune Polyendocrinopathy Type 2 (PEA Type) Associated with Biermer's Disease: Report of a Case and Review of the Literature

Autoimmune Polyendocrinopathy Type 2 (PEA Type) Associated with Biermer's Disease: Report of a Case and Review of the Literature

Interleukin (IL)-23, IL-31, and IL-33 Play a Role in the Course of Autoimmune Endocrine Diseases.

Interleukins (IL)-23, 31, and 33 are involved in the regulation of T helper 17 (Th17)/regulatory T (Treg) cells balance. The role of IL-23, 31 and 33 in non-endocrine autoimmune diseases has been confirmed. Data on the involvement of these cytokines in endocrine autoimmune diseases are limited. This study aimed to determine the involvement of cytokines regulating the T helper 17 (Th17)/regulatory T (Treg) cells axis in the course of autoimmune endocrine diseases. A total number of 80 participants were divided into 4 groups: the autoimmune polyendocrine syndrome (APS) group consisting of APS type 2 (APS-2) and type 3 (APS-3) subgroups, the Hashimoto's thyroiditis (HT) group, the Graves' disease (GD) group and the control (C) group. Fifteen cytokines related to Th17 and Treg lymphocytes were determined in the serum of all participants. Higher levels of IL-23 and IL-31 were found in the APS, GD, and HT groups compared to the C group. Higher levels of IL-23 and IL-31 were also observed in the APS-2 group, in contrast to the APS-3 group. Correlation analysis of variables in the groups showed a statistically significant correlation between the cytokines IL-23, IL-31, and IL-33 in the APS and APS-2 groups, but no correlation in the APS-3 and C groups. IL-23 and IL-31 are independent factors in the course of HT, GD, and APS-2, in contrast to APS-3. The positive correlation between IL-23 and IL-31, IL-23 and IL-33, and between IL-31 and IL-33 in the APS, APS-2 groups, but the lack of correlation in the APS-3 and C groups may further suggest the involvement of these cytokines in the course of Addison's disease.

A patient diagnosed with new-onset type 1 diabetes and Addison's disease at initial presentation.

A previously healthy 17-year-old female presented to the emergency department with complaints of vomiting, shortness of breath, and tachycardia. She was found to have an elevated blood glucose and was admitted for presumed new onset type 1 diabetes mellitus (T1DM). During the admission, she was noted to have frequent episodes of hypoglycemia despite conservative insulin dosing and high urine output with glucosuria, which seemed out of proportion to her glucose levels and fluid status. She also had persistent hyponatremia despite normalization of blood glucose. Further work-up was initiated to investigate alternative or additional diagnoses to explain these atypical findings. Adrenocorticotropic hormone (ACTH) level was elevated, consistent with the diagnosis of Addison's disease, which led to the subsequent diagnosis of autoimmune polyglandular syndrome type II (APS-2). This is one of the first reports in the literature of concurrent diagnosis of T1DM and Addison's disease at initial presentation and demonstrates the importance of not anchoring to one diagnosis. This case shows the importance of considering multiple diagnoses and investigating atypical signs and symptoms. This case highlights the importance of a thorough history including review of systems. Hyponatremia and recurrent hypoglycemia in a person with type 1 diabetes should raise suspicion for adrenal insufficiency. This case makes us consider the screening for Addison's disease in a person with new onset type 1 diabetes in addition to autoimmune thyroid disease and celiac disease. People with an autoimmune disease should be monitored for other autoimmune diseases in the future.

Clinical case of autoimmune polyglandular syndrome type II

The peculiarities of clinical symptoms and the difficulties of diagnosing have been considered on the clinical example of manifestations of autoimmune polyglandular syndrome type II in a young woman. Autoimmune polyglandular syndrome type II is a rather rare pathology, its prevalence is 1 : 20.000 cases of the population. The diagnosis of this disease is determined by the presence of insufficiency of at least two endocrine glands with mandatory adrenal insufficiency. The second component of the disease can be any autoimmune thyroid disease or type 1 diabetes mellitus, which is also autoimmune in nature, or both conditions. Adrenal insufficiency is the initial manifestation of this syndrome in approximately 50% of patients, occurs simultaneously with autoimmune thyroiditis or type 1 diabetes in 20% of patients, the remaining 30% of patients may have a different sequence of manifest components of autoimmune polyglandular syndrome type II. In this article, special attention is paid to the importance of careful monitoring of patients with at least one autoimmune disorder of endocrine organ. The data presents in detail a history of patient who had only type 1 diabetes and autoimmune thyroiditis for 7 years, and the manifestation of adrenal insufficiency was registered 7 years after the manifestation of the primary components of autoimmune polyglandular syndrome type II. The authors highlighted diagnostically significant changes in laboratory methods. The analysis has been performed for the literature data, related to the disease. The necessary to observe patients regularly for quick diagnosis and to reduce the risk of developing both immediate and delayed complications has been emphasized. Special attention should be paid to the examination of relatives of the first line of kinship among patients with the established diagnosis of autoimmune polyglandular syndrome type II for the presence of possible heredity.
  

Autoimmune polyendocrine syndrome type 1 in an 11-year- old boy

    Autoimmune polyendocrine syndrome type 1 is a rare autosomal recessive hereditary pathology — a defect in the autoimmune regulator gene (AIRE), which develops with endocrine and non-endocrine manifestations in childhood. The disease is characterized by clinical polymorphism, which makes timely diagnosis difficult. The article describes a clinical case of an 11-year-old patient with autoimmune polyendocrine syndrome type 1, in whom the course of the disease was erased for a long period. The high quality of life of such patients is possible with timely, individually selected substitution therapy, followed by dispensary observation.

Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1

Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1

Challenges and pitfalls in the management of endocrine toxicities from immune checkpoint inhibitors: a case presentation of synchronous thyrotoxicosis and primary adrenal insufficiency in a melanoma patient.

Immune checkpoint inhibitors have revolutionized the therapeutic approach to several solid tumors, becoming the standard of care for cancer treatment in different disease settings. Despite the fact that these agents are better tolerated than conventional chemotherapy, their use is associated with a specific toxicity profile, so-called immune-related adverse events (irAEs), that can involve several organs. Endocrine irAEs are among the most frequent toxicities (around 10 to 16%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Some of them may be life-threatening if not promptly recognized (such as diabetic ketoacidosis and acute adrenal crisis). A 55-year-old woman with a personal history of euthyroid Hashimoto's thyroiditis was diagnosed with a metastatic melanoma, BRAF wild type. Under treatment with anti-PD-1 pembrolizumab, she developed thyrotoxicosis followed by hypothyroidism due to destructive thyroiditis and concurrent primary adrenal insufficiency due to adrenalitis. The simultaneous occurrence of adrenal and thyroid autoimmune diseases, resembling autoimmune polyendocrine syndrome type 2, may occur as a rare but serious side effect of ICI treatment. It often presents with abrupt onset and rapid evolution towards polyglandular insufficiency. Physicians should be aware of the potential association of two or more endocrine disorders and careful monitoring of endocrine function is needed during ICI therapy.

Schmidt's Syndrome: An Uncommon Cause of Spontaneous Hypoglycemia

AbstractSchmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

Analysis of the AIRE Gene Promoter in Patients Affected by Autoimmune Polyendocrine Syndromes.

Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1-APS4. APS1 is caused by AIRE gene loss of function mutations, while the genetic background of the other APS remains to be clarified. Here, we investigated the potential association between AIRE gene promoter Single Nucleotide Polymorphisms (SNPs) and susceptibility to APS. We sequenced the AIRE gene promoter of 74 APS patients, also analyzing their clinical and autoantibody profile, and we further conducted molecular modeling studies on the identified SNPs. Overall, we found 6 SNPs (-230Y, -655R, -261M, -380S, -191M, -402S) of the AIRE promoter in patients' DNA. Interestingly, folding free energy calculations highlighted that all identified SNPs, except for -261M, modify the stability of the nucleic acid structure. A rather similar percentage of APS3 and APS4 patients had polymorphisms in the AIRE promoter. Conversely, there was no association between APS2 and AIRE promoter polymorphisms. Further AIRE promoter SNPs were found in 4 out of 5 patients with APS1 clinical diagnosis that did not harbor AIRE loss of function mutations. We hypothesize that AIRE promoter polymorphisms could contribute to APS predisposition, although this should be validated through genetic screening in larger patient cohorts and in vitro and in vivo functional studies.

Primary Adrenal Insufficiency in Autoimmune Polyglandular Syndrome Type 1 - A Case Report and Literature Review

Primary Adrenal Insufficiency in Autoimmune Polyglandular Syndrome Type 1 - A Case Report and Literature Review

Increased type 1 inflammation in gynecologic cervicovaginal samples in patients with APS-1

Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates excessive T-cell IFN-γ secretion and ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. Whether IL-17 paucity, increased type I inflammation, or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1 is debated. Our aim was to characterize the immunologic features in the cervicovaginal mucosa of females with APS-1. Vaginal fluid was collected with a flocked swab from 17 females with APS-1 and 18 controls, and cytokine composition was analyzed using Luminex (Luminex Corporation, Austin, Tex). Cervical cell samples were obtained with a cervix brush from 6 patients and 6 healthy controls and subjected to transcriptome analysis. The vaginal fluid samples from patients with APS-1 had IFN-γ concentrations comparable to those of the controls (2.6 vs 2.4 pg/mL) but high concentrations of the TH1 chemokines CXCL9 and CXCL10 (1094 vs 110 pg/mL [P< .001] and 4033 vs 273 pg/mL [P= .001], respectively), whereas the IL-17 levels in the samples from the 2 groups were comparable (28 vs 8.8 pg/mL). RNA sequencing of the cervical cells revealed upregulation of pathways related to mucosal inflammation and cell death in the patients with APS-1. Excessive TH1 cell response appears to underlie disruption of the mucosal immune responses in the genital tract of patients with APS-1 and may contribute to susceptibility to candidiasis in the genital tract as well.

Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients.

Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant. We analyzed a large dataset including prospectively collected data from 920 consecutive adult CD patients diagnosed in a third-level Italian institution in the 2013-2023 period, The prevalence of isolated autoimmune endocrine diseases and APS were collected. A total of 262 (28.5%) CD patients had at least one associated AED, with AIT (n = 223, 24.2%) and T1DM (n = 27, 2.9%) being the most frequent conditions. In most cases (n = 173, 66%), AEDs were diagnosed after CD. Thirteen patients (1.4%) had at least two of the requested three endocrinopathies, satisfying the diagnosis of type 2 APS. APS-2 is a rare but not exceptional occurrence among Italian CD patients, underscoring the intricate and multifaceted nature of autoimmune disorders. Periodic evaluations of thyroid function and glycaemia should be recommended after the diagnosis of CD together with testing for autoantibodies that may be helpful in assessing disease risk before disease onset. Likewise, implementation of a systematic screening for CD amongst T1DM and other autoimmune endocrine diseases are paramount.