Autoimmune Polyglandular Syndrome Research Articles

Use of rituximab in the of immunoinflammatory rheumatic diseases combined with Graves' disease (autoimmune polyglandular syndrome in adults): case report and literature review

Rituximab (RTM) is a chimeric (murine and human) monoclonal antibody against B-lymphocytes (CD20). RTM is widely used in hematology for lymphoproliferative diseases and in rheumatology for rheumatoid arthritis, Sjögren's disease, some types of vasculitis and systemic connective tissue diseases. The administration of RTM is associated with a depletion of B-cells mediated by the regulation of apoptosis and cytotoxic effects via complement-dependent and antibody-dependent mechanisms. Considering the pathogenesis of autoimmune damage in Graves' disease (GD), an autoimmune thyroid disease associated with thyrotoxicosis, the use of RTM could be effective in this pathology. We present three patients with a combination of diffuse toxic goiter and rheumatic pathology treated with RTM; different outcomes of GD were observed.

A-9-Years-Old Female with Diabetes Mellitus Type 1 with Hyperthyroidism

Diabetes Mellitus Type 1 (DMT1) and thyroid disease can occur together, which is defined as a variant of autoimmune polyglandular syndrome type 3. It is known that the action of insulin and thyroid hormones affect cellular metabolism, thyroid hormones contribute to carbohydrate metabolism and pancreatic function. Since the thyroid gland plays a central role in the regulation of metabolism, abnormal thyroid function can have a major impact on the control of diabetes and poor glycemic control can cause alterations in thyroid hormone. A female, 9 years old, with decreased consciousness. Previous medical history, polyuria, increased appetite, and drastic weight loss. She also complained of sweating even in a cold room and was often emotional. On physical examination, there was fever, shortness of breath, tachycardia, and a soft and diffused slightly enlarged thyroid gland, with no bruit on auscultation. Laboratory tests showed blood glucose levels at 739 mg/dL, HbA1c 9.2%, C-peptide 0.2 ng/mL, TSH levels 0.01 µIU/mL, FT4 levels 2.77 ng/dL, the presence of metabolic acidosis, proteinuria, glucosuria, and ketonuria. Thyroid dysfunction will have a negative effect on DM control while poor glucose control will harm the work of thyroid hormones. Improvement in glycemic control and routine insulin injection with the right dose will reduce the risk of diabetic vascular and metabolic complications onset and progression.

The Putative Role of TIM-3 Variants in Polyendocrine Autoimmunity: Insights from a WES Investigation.

Autoimmune polyglandular syndrome (APS) comprises a complex association of autoimmune pathological conditions. APS Type 1 originates from loss-of-function mutations in the autoimmune regulator (AIRE) gene. APS2, APS3 and APS4 are linked to specific HLA alleles within the major histocompatibility complex, with single-nucleotide polymorphisms (SNPs) in non-HLA genes also contributing to disease. In general, variability in the AIRE locus and the presence of heterozygous loss-of-function mutations can impact self-antigen presentation in the thymus. In this study, whole-exome sequencing (WES) was performed on a sixteen-year-old female APS3A/B patient to investigate the genetic basis of her complex phenotype. The analysis identified two variants (p.Arg111Trp and p.Thr101Ile) of the hepatitis A virus cell receptor 2 gene (HAVCR2) encoding for the TIM-3 (T cell immunoglobulin and mucin domain 3) protein. These variants were predicted, through in silico analysis, to impact protein structure and stability, potentially influencing the patient's autoimmune phenotype. While confocal microscopy analysis revealed no alteration in TIM-3 fluorescence intensity between the PBMCs isolated from the patient and those of a healthy donor, RT-qPCR showed reduced TIM-3 expression in the patient's unfractionated PBMCs. A screening conducted on a cohort of thirty APS patients indicated that the p.Thr101Ile and p.Arg111Trp mutations were unique to the proband. This study opens the pathway for the search of TIM-3 variants possibly linked to complex autoimmune phenotypes, highlighting the potential of novel variant discovery in contributing to APS classification and diagnosis.

Systematic analysis and network mapping of disease associations in autoimmune polyglandular syndrome.

The purpose of our work was to provide a data-driven perspective to APS, a complex autoimmune disorder, supplementing traditional clinical observations. Medical records of 7559 patients were analyzed, autoimmune origin was proved in 3180 cases of which 380 (12%) had APS. Associations of component disorders were investigated by computational methods to reveal typical patterns of disease development. Twenty-eight distinct autoimmune disorders were diagnosed forming 113 combinations. The 10 most frequent combinations were responsible for 51,3% of cases. HT and GD were differentiated as main cornerstones of APS, sharing several comorbidities. HT was the most common manifestation (67.4%), followed by GD (26.8%) and T1D (20.8%). APS started significantly earlier in men than in women. Thyroid autoimmunity was frequently linked to gastrointestinal and systemic manifestations and these patterns of associations substantially differed from that of T1D, AD or CeD when present as first manifestations, suggesting the possibility of a common biological cause. APS is more frequent than reported. Classifying APS requires a shift of perspective towards disease associations rather than disorder prevalence.

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (< 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (<1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

8705 Autoimmune Polyglandular Syndrome Type 2 Presenting As Recurrent Cardiac Tamponade

Abstract Disclosure: E.M. Niedzialkowska: None. D. Shelden: None. Introduction: Autoimmune polyglandular syndrome type 2 (APS2) is a rare endocrinopathy with co-occurrence of autoimmune adrenal insufficiency, autoimmune thyroiditis and/or type 1 diabetes. In rare cases, APS2 can predispose patients to recurrent pericardial effusion and tamponade. Case presentation: 32 y.o male with medical history of hypothyroidism on replacement therapy diagnosed 2 weeks prior to admission presented with progressive dyspnea and hypotension. The patient was found to have pericardial effusion with tamponade requiring pressor support. Initial lab tests showed TSH 148.7 uIU/ml (N 0.4-4.5), free t4 0.7 ng/dl(N 0.7-1.5 ), free t3 2 pg/ml (N 1.7-3.5), Hb a1c 4.7% (N <5.6%), thyroglobulin antibody 851 IU/ml (N <20), TPO antibody >1 000 IU/ml (N<=35), TSI 0.1 IU/l (<0.1), sodium 127 mmol/l (N 135-145), and a negative adrenal antibody panel. The patient was started on IV levothyroxine (400 mcg daily) and stress dose steroids in the setting of shock requiring 4 pressors. Shock resolved after pericardiocentesis and the patient was weaned off pressor support. Pericardial fluid showed neutrophil predominance and was negative for an infectious process, lab tests showed negative ANA, ANCA and GBM. The day following admission lab tests showed TSH of 23.86 uIU/ml, ft4 1.3 ng/dl, the patient was transitioned to oral levothyroxine 125 mcg and the steroid regimen was tapered and discontinued. Follow up tests showed normal TSH and resolution of pericardial effusion. Four weeks after initial admission the patient was readmitted due to hypotension. Laboratory tests showed random cortisol <1.0 ug/dl (N 2.9-19.4), ACTH 17 pg/ml (N 6-48), adrenal antibody titers 1:20 (N < 1:10), cosyntropin stimulation test was positive for adrenal insufficiency and the patient was started on steroid regimen with symptomatic improvement. He was diagnosed with APS type 2 based on his constellation of endocrinopathies. Repeat echocardiogram was negative for pericardial effusion. Two months later, the patient presented with chest pain. Imaging was positive for recurrent pericardial effusion requiring pressor support and pericardiocentesis. The patient was subsequently started on colchicine. Infectious and rheumatologic workup continued to be negative. The patient did not exhibit symptoms of connective tissue disease. Seven months after the initial presentation the patient was readmitted with COVID-19 infection complicated by hypotension and a small pericardial effusion. Symptoms improved after initiation of stress dose steroids. Conclusion: Cardiac tamponade is a rare presentation of APS2 with 9 cases reported in the literature up to date. Increased incidence of pericardial effusion is presumed to be a result of autoimmune inflammation leading to fluid accumulation. The patients are prone to tamponade due to intravascular volume depletion, decreased vascular tone and impaired stress response. Presentation: 6/3/2024

7658 A Case of Recurrent Cardiac Tamponade as Initial Presentation of Primary Adrenal Insufficiency

Abstract Disclosure: A. Farooq: None. A. Ghumatkar: None. J. Snitzer: None. Introduction:Cardiac tamponade, a life-threatening emergency, can be associated with primary adrenal insufficiency (Addison Disease), and accurate diagnosis requires a high degree of clinical suspicion in patients with uncertain etiology and nonspecific signs and symptoms. Case Presentation:A 58-year-old female with a history of Hashimoto thyroiditis was evaluated in the hospital for two episodes of cardiac tamponade requiring emergent pericardiocentesis within one month. The patient had been experiencing symptoms of fatigue, nausea, lightheadedness, dizziness, hiccups, and tanned skin for the past year. She also had a recent flu-like illness with nausea and vomiting four months before her current presentation. Her vitals were notable for hypotension during these episodes. Her lab work showed hyponatremia (128 mEq/L, reference range: 136-145 mEq/L) with normal potassium and glucose levels. Her thyroid function tests were within normal limits on her home levothyroxine dosage (TSH 4.588 IU/ml, reference range: 0.5-8.9 IU/ml). An ACTH stimulation test was performed based on the patient's clinical presentation, consistent with adrenal insufficiency. Her baseline cortisol level was 5.9 mcg/dL (reference range: 6.7-22 mcg/dL), a post-ACTH stimulation level of 6.7 mcg/dL after 30 minutes, and 6.0 mcg/dL after 60 minutes. Her 21 alpha-hydroxylase antibody titer was also positive for Addison Disease (231U/mL, reference range <1 IU/mL). A CT scan of the abdomen with intravenous contrast was done, which revealed no abnormality of the adrenal glands. She was treated with stress doses of hydrocortisone during hospitalization and discharged with maintenance dosage and follow-up with endocrinology. She had another episode of acute adrenal crisis about a month later but had no pericardial effusion this time and responded well to the treatment with stress doses of steroids. She has remained healthy at 14 years of follow-up. Conclusion: This case emphasizes the need to consider adrenal insufficiency in the evaluation of cardiac tamponade or pericardial effusions, especially in patients with existing autoimmune glandular disorders. This patient may have autoimmune polyglandular syndrome type 2 (APS-2), which is a cluster of two or more endocrine glandular disorders primarily diagnosed in adulthood and predominant in females. The risk of adrenal crisis is more than twofold in Addison disease due to APS-2. Lastly, this case highlights that hiccups can be related to adrenal insufficiency, with pathophysiology possibly involving diaphragmatic irritation due to adrenal inflammation that resolves with treatment. Presentation: 6/3/2024

8746 Primary Prevention and Early Intervention for Cardiovascular Disease in Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: V.N. Flores-Robles: None. Y. Fuentes-Rosa: None. M. Sanchez-Cordero: None. D.A. Lopez: None. M. Carrero-Quinones: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is an autoimmune syndrome that is known for lymphocytic infiltration causing organ-specific damage. It can include primary adrenal insufficiency (Addison's disease), type 1 diabetes mellitus (T1DM), autoimmune thyroid disease-causing Grave’s disease, or hypothyroidism, and can be diagnosed when two out of these three pathologies are present. Carpenter syndrome, a type of PAS-2, is described as the triad of Addison's disease, autoimmune thyroid disease, and T1DM. Its initial manifestation can be associated with non-endocrine and endocrine disorders as in autoimmune thyroid disease, T1DM, primary hypogonadism, and diabetes insipidus. It is well documented that uncontrolled diabetes mellitus can accelerate the progression of cardiovascular disease of co-existing coronary artery disease, but documentation that Addison’s disease may accelerate the progression is scant with only ten cases documented. On the other hand, there are no documented cases of the presence of coronary artery disease in patients with PAS-2. Case report: This case involves a 66-year-old Hispanic male with a past medical history of hypertension, and PAS-2, presenting with Addison’s disease, type 1 diabetes mellitus, and hypothyroidism. The initial presentation at the hospital was that of a complete atrioventricular block that required pacemaker placement. Cardiology services were consulted as the patient also had a positive stress test and eventually cardiac catheterization was done as further workup. Cardiac catheterization showed obstruction of the left main coronary artery of 80% and left circumflex with mild disease, that required coronary artery bypass (CABG). A 2D ECHO was done for further evaluation of cardiac function and findings were pertinent for an ejection fraction of 65-70%, mild concentric hypertrophy of the left ventricular wall, and left ventricular diastolic function with impaired relaxation pattern. The patient underwent the CABG procedure without any complications. He has been followed up outpatient and remains without any symptoms or pertinent presentation. Early intervention in this patient with PAS-2 prevented any further cardiovascular complications. Conclusion: Patients with PAS-2 may have a predisposition to developing coronary artery disease due to concomitant endocrinopathies that independently increase the risk of cardiovascular disease. This promotes further investigation into the primary prevention of cardiovascular disease in patients presenting with PAS-2. Taking into consideration the increased risk and/or progression of cardiovascular disease in these patients, early intervention and evaluation by cardiology services should be suggested as it may decrease their morbidity or mortality. Presentation: 6/2/2024

Whitaker syndrome: A case report of autoimmune polyendocrine syndrome type 1 with dilated cardiomyopathy.

This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS-1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow-up are crucial in managing these atypical presentations to optimize patient outcomes. APS-1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS-1 are infrequently reported in the literature. We present a case of a 28-year-old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x-ray showed left-sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS-1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS-1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients.

Manifestations of Endocrine Disease in the Lower Extremities: Beyond the Diabetic Foot.

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.

Polyglandular Syndrome type III in a young patient: case report

Introduction: Autoimmune polyglandular syndromes (APS) are rare diseases defined by the coexistence of at least two autoimmune endocrine diseases. Objective: To describe a case of type III polyglandular syndrome in a young patient. Case report: Female, 37 years old, with hypothyroidism, presented with a weight loss of 9 kg, daily vomiting, asthenia, fatigue, and postprandial fullness for 3 months. He also reported arthritis in his wrists, shoulders, and hips. In laboratory tests, macrocytic and hyperchromic anemia associated with leukopenia, as well as hypovitaminosis B12, was observed. Pernicious anemia was investigated as the cause of this deficiency. Upper digestive endoscopy showed moderate gastritis – histopathological with gastric atrophy, positive anti-intrinsic factor antibody. Due to inflammatory arthralgia, ANA was requested, with an associated positive anti-dsDNA result of 1:80. In the EULAR/2019 diagnostic criteria for Systemic Lupus Erythematosus (SLE), she presented 14 points, thus she was diagnosed with SLE, and hydroxychloroquine (HXC) was started. Conclusion: SPA is rare, mainly in association with non-glandular autoimmunity, following an early diagnosis.

Complexity and multimorbidity in autoimmune polyendocrine syndrome type 2 - a case report

Complexity and multimorbidity in autoimmune polyendocrine syndrome type 2 - a case report

Review of clinical practice guidelines for hypoparathyroidism

Hypoparathyroidism is an endocrine disease characterized by reduced production of parathyroid hormone by the parathyroid glands or tissue resistance to its action. This is accompanied by disturbances in phosphorus-calcium metabolism.The main cause of hypoparathyroidism is damage or removal of the parathyroid glands during surgery on the neck organs. Autoimmune hypoparathyroidism is the second most common form of the disease, which occurs, as a rule, within the autoimmune polyglandular syndrome type 1.The development of chronic hypoparathyroidism of any etiology requires lifelong appointment of multicomponent therapy, as well as careful monitoring and an individual approach. In the absence of adequate dynamic monitoring, multiple complications develop from vital organs, in particular calcification of the urinary system, soft tissues and the brain; cardiovascular pathology; visual disturbances; muscle and bone diseases leading to decreased quality of life of patients.Thus, timely diagnosis, rationally selected drug therapy and competent patient management will reduce the risks of complications, improve the prognosis, and reduce the frequency of hospitalizations and disability of patients with chronic hypoparathyroidism.The article presents the main recommendations of the new project of clinical guidelines for patients with hypoparathyroidism, approved by the Ministry of Health of the Russian Federation in 2021. They include the algorithms of diagnosis, treatment and dynamic monitoring of hypoparathyroidism, as well as management of postsurgical hypocalcemia and medical care of and the disease during pregnancy.

A Comprehensive Overview of a Rare Case of Type 2 Autoimmune Polyglandular Syndrome

Introduction: Polyglandular deficiency syndromes reflects a wide spectrum of disorders. Autoimmune polyglandular syndrome (APS) is a rare condition generally divided into two categories APS -1 and APS -2.  Case Report: We report a case of APS-2 in a 28 years old male with marfanoid habitus, presented with significant weight loss, fever and hemoptysis. upon examination, he had exophthalmos, pallor, marfanoid habitus with systolic murmur in all cardiac areas and coarse crepitation in left hemithorax. Laboratory evaluation revealed left upper lobe pneumonia secondary to Acinetobacter. Further evaluation revealed severe hyperthyroidism, anti TPO, TRAB antibody was elevated, megaloblastic anemia with atrophic gastritis and positive 21 alpha hydroxylase.  Diagnosis: The above findings were consistent with the diagnosis of APS type 2 (Graves’ Disease, Adrenal Insufficiency, Pernicious Anaemia, Vitiligo). The presence of two or more endocrine deficiencies defines APS-2 which may include graves’ disease, type 1 Dm, primary adrenal insufficiency, hypogonadism and features like pernicious anaemia, vitiligo and alopecia.  Conclusion: Circulating antibodies may precede development of clinical disease by many years but would allow clinician to follow the patient and identify the disease onset at the earliest.

A Rare Case of an Autoimmune Polyglandular Syndrome Type 2 During Pregnancy

Autoimmune polyglandular syndromes (APS) are a rare heterogeneous disorders characterized by combining two or more organ-specific endocrinopathies. During pregnancy, only a few cases of these syndromes have been described. We report a case of autoimmune polyglandular syndrome type 2 presenting during pregnancy and complicated in the immediate postpartum by a severe polyserositis.

Late-onset Schmidt's Syndrome Presenting with Severe Hyponatremia: A Case Report.

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. 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. 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].

Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis).

Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000-March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7-23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22-79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18-75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6-7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10-20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison's disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of "endocrine petrified ear" and a workflow algorithm to assess the potential hormonal/metabolic background in PE.

Cardiac tamponade - a rare cause of sudden death in autoimmune polyglandular syndrome.

A 27-year-old male died suddenly due to cardiac tamponade arising from pericarditis complicating autoimmune polyglandular syndrome (APS) type 2. He had a history of primary Addison disease and autoimmune hypothyroidism which were corroborated at autopsy. In addition a florid fibrinous pericarditis was associated with 287g of turbid fluid in the pericardial sac. Although pericarditis with tamponade is a potential complication of APS, it has rarely if ever, been reported as a cause of sudden death. Lethal mechanisms may involve both compressive and restrictive effects.

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study

Aim of the studyThe primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. Material and methodsWe retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. ResultsPatients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16–30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). ConclusionsWe found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16–30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

Limb-girdle muscle dystrophy as a novel rare component of autoimmune polyglandular syndrome type 1

Limb-girdle muscle dystrophy as a novel rare component of autoimmune polyglandular syndrome type 1