SAT-683 A Case of Autoimmune Polyglandular Syndrome Type 2 and Guillain-Barré Syndrome

Disclosure: F. El Sayed: None. K. Estrada: None. Background: Autoimmune polyglandular syndrome type 2 (APS-2) is a rare condition characterized by the coexistence of autoimmune adrenal insufficiency (Addison's disease), autoimmune thyroid disease, and often type 1 diabetes mellitus. Viral infections are known to trigger autoimmune diseases, with some studies suggesting an increased risk of autoimmune conditions following infections, including SARS-CoV-2. However, the direct association between COVID-19 and APS-2 remains underexplored. Case Description: A 47-year-old male with a history of gastroesophageal reflux disease (GERD) and Raynaud’s disease presented with dizziness, hypotension, unintentional weight loss, increased salt cravings, and dyspnea on exertion. His daughter’s pediatrician observed skin hyperpigmentation, prompting further evaluation. He had a history of SARS-CoV-2 infection six months prior and had received a 5-day course of steroids. Family history was notable for scleroderma and possible thyroid disease in his mother.The primary care provider measured an 8 am cortisol, which was low (4.1 µg/dL), alongside an elevated TSH (13.48 uIU/L) and low free T4 (0.91 ng/dL), prompting referral to endocrinology. On exam, he was hypotensive (90/60 mmHg), tachycardic (pulse 112), and had diffuse skin hyperpigmentation but was not in acute distress.Laboratory findings showed hyponatremia (sodium 133 mmol/L), high-normal potassium (4.7 mmol/L), suppressed aldosterone (<3 ng/dL), elevated renin (701.1 pg/mL), elevated ACTH (1,370 pg/mL), and low morning cortisol (2.1 µg/dL), suggestive of Addison’s disease. Testing for 21-hydroxylase antibodies was positive. Thyroid tests revealed elevated TSH (17.62 uIU/mL), low free T4 (0.49 ng/dL), and positive thyroid peroxidase antibodies (92 IU/mL), confirming autoimmune hypothyroidism. Screening for type 1 diabetes was positive for GAD65 antibodies (120 IU/mL) and a hemoglobin A1c of 5.6%, indicating latent autoimmune diabetes (LADA). Diagnosis and Management: The patient was diagnosed with Autoimmune Polyglandular Syndrome Type 2, consisting of Addison’s disease, autoimmune hypothyroidism, and stage 1 LADA. He was started on hydrocortisone, fludrocortisone, and levothyroxine. His glucose and hemoglobin A1c are being monitored. Discussion and Conclusion: This case suggests a possible link between SARS-CoV-2 and APS-2. Viral infections, including COVID-19, may trigger autoimmune responses in genetically predisposed individuals. The patient’s history of COVID-19, followed by multiple autoimmune conditions, supports this hypothesis. This case contributes to the growing literature on post-viral autoimmune diseases and highlights the need for further research into SARS-CoV-2 as an autoimmune trigger. Clinicians should be vigilant in recognizing and managing post-COVID autoimmune endocrinopathies. Presentation: Sunday, July 13, 2025

Autoimmune diseases and sarcoidosis may be related and, especially, the association between sarcoidosis and autoimmune thyroid disease has long been recognized. The frequency and type of endocrine autoimmunity was examined in a series of Swedish patients with sarcoidosis. Of all patients (N = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males and 34 females; median age at the time of the study 48 years. range 22-81 years) were examined at the Department of Endocrinology, Malmö University Hospital, in the present study. Fifteen patients (19.2%) had clinical or serological evidence of endocrine autoimmunity. Two patients had Addison's disease, both with polyglandular autoimmune (PGA) syndrome type II: evidence of thyroid autoimmunity was found in 13 patients, eight with clinical autoimmune thyroid disease (ATD) (two with Graves' disease and six with autoimmune thyroiditis), of whom two had PGA syndrome type III, and five with isolated positive thyroid serology; two patients had insulin-dependent diabetes mellitus and one had premature ovarian failure. The frequencies of Addison's disease, clinical ATD and PGA syndrome type II were significantly higher compared with the frequencies found in the general population. In conclusion, a high frequency of endocrine autoimmunity in patients with sarcoidosis, occurring in about 20% of the cases, was demonstrated. Thyroid autoimmunity and polyglandular autoimmune syndromes occurred most frequently. Complex immunological and genetic mechanisms might explain the association of sarcoidosis and endocrine autoimmune diseases.

Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other than Addison’s disease and hypoparathyroidism. We evaluated the prevalence and repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in 107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis, non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24), and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients, the rate of levothyroxine treatment was greater in THAb-positive patients compared to THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03–1.81). Not unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3, namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and 1.8 ± 0.3 vs. 1.5 ± 0.2 μg/kg body weight, P = 0.0005 and P = 0.004). Almost half of PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis or celiac disease is present. A prospective study would confirm whether THAb positivity predicts greater likelihood of requiring levothyroxine treatment.

The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed.

Autoimmune polyglandular syndrome (APS) type 2 is defined by the manifestation of at least two autoimmune endocrine diseases. Only few data exist on genetic associations of APS type 2. In this controlled study, 98 patients with APS type 2, 96 patients with type 1 diabetes (T1D), and 92 patients with autoimmune thyroid disease, both as a single autoimmune endocrinopathy, were tested for association with alleles of the human leukocyte antigen (HLA) class II loci DRB1, DQA1, and DQB1. Patients with APS type 2 had significantly more often the alleles DRB1*03 (P(c) < 0.0001), DRB1*04 (P(c) < 0.000005), DQA1*03 (P(c) < 0.0001), and DQB1*02 (P(c) < 0.05), when compared with controls. Less frequent in APS were DRB1*15 (P(c) < 0.05), DQA1*01 (P(c) < 0.0005), and DQB1*05 (P(c) < 0.005). With regard to frequency and linkage of these alleles, the susceptible haplotypes DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*0401/04-DQA1*0301-DQB1*0302 were deduced. Protective haplotypes in this study were DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*0101-DQA1*0101-DQB1*0501. Comparing APS patients with vs without AD, no significant differences regarding HLA class II alleles were noted in our collective. Patients with T1D as a singular disease had the same susceptible and protective HLA alleles and haplotypes. The prevalence of DRB1*03 and DRB1*04 in APS patients was not because of the presence of diabetes, as the APS type 2 patients without diabetes had the same allele distribution. In conclusion, these data suggest a common immunogenetic pathomechanism for T1D and APS type 2, which might be different from the immunogenetic pathomechanism of other autoimmune endocrine disease.

BackgroundGuillain‐Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin is beneficial in other autoimmune diseases.ObjectivesWe aimed to determine the efficacy of intravenous immunoglobulin for Guillain‐Barré syndrome.Search strategyWe updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register, MEDLINE and EMBASE in June 2009 using the terms 'Guillain‐Barré syndrome' and 'acute polyradiculoneuritis' combined with 'intravenous immunoglobulin'.Selection criteriaWe included randomised and quasi‐randomised trials.Data collection and analysisTwo authors independently selected papers, extracted data and assessed quality.Main resultsAnother Cochrane systematic review has shown that plasma exchange significantly hastens recovery. In this review, five trials compared intravenous immunoglobulin with plasma exchange in 536 severely affected, mostly adult participants. The mean difference of change in a seven‐grade disability scale after four weeks was not significantly different between the two treatments: 0.02 (95% CI 0.25 to ‐0.20) of a grade more improvement in the intravenous immunoglobulin than the plasma exchange group. There were also no statistically significant differences in the other measures considered. Three studies including a total of 75 children suggested that intravenous immunoglobulin significantly hastens recovery compared with supportive care.In one trial involving 249 participants comparing plasma exchange followed by intravenous immunoglobulin with plasma exchange alone, the mean grade improvement was 0.2 (95% CI ‐0.14 to 0.54) more in the combined treatment group than in the plasma exchange alone group, not significantly different but not excluding the possibility of significant extra benefit. Another trial with 37 participants comparing immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone did not reveal significant extra benefit from the combined treatment.Small trials in children showed a trend towards more improvement with high‐dose compared with low‐dose intravenous immunoglobulin and no significant difference when the standard dose was given over two days rather than five days.Authors' conclusionsA previous Cochrane review has shown that plasma exchange hastens recovery compared with supportive treatment alone. There are no adequate comparisons of intravenous immunoglobulin with placebo in adults but this review provides moderate quality evidence that, in severe disease, intravenous immunoglobulin started within two weeks from onset hastens recovery as much as plasma exchange. Adverse events were not significantly more frequent with either treatment but intravenous immunoglobulin is significantly much more likely to be completed than plasma exchange. Also according to moderate quality evidence, giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit. In children, according to low quality evidence, intravenous immunoglobulin probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in patients whose treatment starts more than two weeks after onset. Dose‐ranging studies are also needed.Plain Language SummaryIntravenous immunoglobulin for Guillain‐Barré syndromeGuillain‐Barré syndrome is an uncommon disease of the peripheral nerves. It causes weakness, numbness and breathing difficulty. Another Cochrane review has shown that plasma exchange (taking blood from one vein, separating the plasma from the blood cells and then returning the blood cells with a plasma substitute into another vein) is more effective than supportive care alone. In adults, moderate quality evidence shows that receiving intravenous immunoglobulin (antibodies that have been purified from donated blood) speeds recovery from severe Guillain‐Barré syndrome as much as plasma exchange. Intravenous immunoglobulin is slightly safer and much easier to give than plasma exchange. According to moderate quality evidence, intravenous immunoglobulin added to plasma exchange is not significantly more effective than either alone. A small amount of evidence suggests that intravenous immunoglobulin is also beneficial in children. More research is needed to determine the best dose in adults and children.

SummaryWe report on a boy of Albanian descent with the history of juvenile myelomonocytic leukemia (JMML). JMML was diagnosed at the age of 17 months and treated by hematopoietic stem cell transplantation (HSCT). At the age of 14.3 years, about 12 years after HSCT, he was hospitalized with an adrenal crisis. Hormone findings were consistent with primary adrenal insufficiency. Autoimmune adrenalitis was confirmed by positive autoantibodies against 21-hydroxylase and adrenal tissue. Since autoimmune Hashimoto thyroiditis was already known from the age of 9 years, we assume that both diseases are part of the spectrum of autoimmune polyglandular syndrome (APS) type 2. APS type 2 is a rare endocrine disease characterized by Addison’s disease along with autoimmune thyroid disease and/or type 1 diabetes.Learning points:Endocrine sequelae after hematopoietic stem cell transplantation (HSCT) are common and can develop over a long period.Primary adrenal insufficiency after HSCT is absolutely rare.The combination of adrenal autoimmune disease and Hashimoto thyroiditis is consistent with autoimmune polyglandular syndrome type 2.

Guillain-Barre syndrome (GBS) is the most common cause of acute neuromuscular paralysis, usually due to acute inflammatory demyelinating polyradiculoneuropathy. The presence of activated T lymphocytes and antibodies against peripheral nerve myelin suggests an autoimmune pathogenesis, although there is wide heterogeneity. Gangliosides are sialylated glycolipids widely distributed in nervous system membranes. GBS is usually preceded by an infection, most frequently Campylobacter jejuni enteritis, but also cytomegalovirus, Mycoplasma pneumoniae or Epstein-Barr virus. Patients with GBS and C. jejuni infection are more likely to have neurophysiological features of axonal neuropathy, antibodies to ganglioside GM1, pure motor GBS, a less elevated CSF protein concentration and a worse outcome than other GBS patients. Although molecular mimicry between peripheral nerve gangliosides and epitopes present on C. jejuni lipopolysaccharide could explain some of these associations, this hypothesis is inadequate to account for many aspects of the pathogenesis of GBS.

SummaryPolyglandular autoimmune syndrome type II is a rare condition defined by the presence of autoimmune primary adrenal insufficiency along with autoimmune thyroid disease and/or type-I diabetes. Onset of these conditions will usually be separated by several years, though in rare instances it can occur simultaneously. This syndrome can also be associated with various non-endocrine autoimmune diseases, such as vitiligo and alopecia. Coeliac disease is less commonly associated with polyglandular autoimmune syndrome type II and is more commonly associated with polyglandular autoimmune syndrome type III. Here we describe an interesting case of a young male presenting with simultaneous manifestation of Addison’s disease and Graves, with coincident asymptomatic coeliac disease, as a rare manifestation of polyglandular autoimmune syndrome type II.Learning points:Polyglandular autoimmune syndrome type II is rare, has female predominance, and peak onset in the third and fourth decades of life.Onset of Addison’s disease will usually precede or follow onset of type-I diabetes or autoimmune thyroid disease by several years in this syndrome.Simultaneous onset can occur, as in this case.Coeliac disease is uncommonly associated with this syndrome.Coeliac disease is more commonly associated with polyglandular autoimmune syndrome type III.Coeliac disease should be screened for in patients with associated autoimmune conditions, such as type-I diabetes or autoimmune thyroid disease.

BackgroundIdiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disease caused by antibodies against platelet glycoproteins. Stiff person syndrome (SPS) is a progressive neurological disorder characterized by axial muscle rigidity and involuntary spasms associated with anti-glutamic acid decarboxylase (GAD) antibodies. Polyglandular autoimmune syndrome type 2 (APS-2) is defined by the occurrence of Addison disease with thyroid autoimmune disease and/or Type 1 diabetes mellitus (T1DM). SPS has been associated with APS-2 as well as to T1DM and autoimmune thyroid disease alone. ITP has been linked T1DM in rare cases as well as autoimmune thyroid disease, yet SPS and ITP have not previously been associated. We present the first reported case to our knowledge of a patient with ITP subsequent to Graves disease, SPS and T1DM. Clinical CaseThe patient is a 35-year-old female evaluated in endocrinology clinic for follow up of Graves disease treated with RAI ablation 5 years prior. She presented with fluctuating muscle rigidity and spasms involving the axial muscles leading to gait disturbance and frequent falls. She displayed the classic “wooden-man” appearance when ambulating first described by Moersch and Wotmann which lead to the name of SPS. She was treated with diazepam due to clinical suspicion for SPS. Neurology was consulted, both the referring physician and neurologist agreed with the diagnosis of SPS. Her symptoms gradually improved yet they have proven to be relapsing and remitting in nature requiring modification of dosing depending on response. 7 years later she was diagnosed with T1DM, presenting to the ED with generalized weakness and fatigue. Initial laboratory work was consistent with DKA. During her hospitalization routine laboratory work showed incidental thrombocytopenia with a platelet count of 15,000. Over the next few days her platelet count dropped to 5,000 prompting diagnostic bone marrow aspiration and biopsy which revealed a hypercellular marrow and adequate megakaryopoiesis. ITP was the working diagnosis and patient was discharged with prednisone. A favorable response to therapy was noted and prednisone was tapered accordingly. 2 years later she presented with a relapse of ITP with a platelet count of 6,000; treatment was initiated with intermittent prednisone and IVIG. At this time T1DM and thyroid disease were well controlled. Serum GAD-antibodies tested after presentation of ITP were >250 IU/ml (0-5.0 IU/ml). ConclusionTo our knowledge ITP has not previously been documented in a patient with SPS. Our goal is to create physician awareness regarding the association between these disorders as well as the need for regular monitoring of patients with an endocrine autoimmune disease. SPS has been linked to APS-2; yet is it possible that SPS can independently be associated with ITP?

The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

Autoimmune polyglandular syndrome (APS) type 2 (Schmidt syndrome) is a disorder characterized by a combination of autoimmune adrenal insufficiency, autoimmune thyroid disease, and type 1 autoimmune diabetes mellitus. We describe the first case of subacute cerebellar syndrome associated with APS type 2. Brain magnetic resonance imaging showed atrophy of the cerebellum and the vermis, as well as of the anterior pituitary gland. Magnetic resonance spectroscopy showed decreased N-acetylaspartate/creatine ratio in the cerebellum and in the pons. Our findings expand the spectrum of neurological deficits in APS type 2 and underlines that cerebellar pathways may be a main target of the disorder.

Polyglandular autoimmune syndrome (PAS) is a rare disease. It is characterized by the association of two or more organ-specific autoimmune disorders. It is estimated that about one-fourth of patients with a single organ-specific autoimmune disease may have or develop other autoimmune diseases. The syndrome can be classified into two types, type I and type II, each with distinct clinical characteristics. PAS type II is the coexistence of adrenal failure with autoimmune thyroid disease, or Type 1 diabetes mellitus (DM). Our patient of PAS Type 2 with hypothyroidism and adrenal failure who achieved significant improvement after receiving cortisone & thyroid replacement therapy. Our patient is a 70 year old male, an atypical presentation, hence emphasizing that clinicians should have high index of suspicion for such condition. Mortality rate is high if patients are not diagnosed promptly and treated early. Patients with PAS require hormone replacement therapy life-long and monitoring for development of other autoimmune diseases.

Recent studies have demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA-4 gene was associated with autoimmune Addison's disease. We analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n repeat) within exon 3 of the CTLA-4 gene in the following groups: 21 English patients with non-associated Addison's disease, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with non-associated Addison's disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non-associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non-associated Addison's disease, 2 with APS2 and 45 controls. The CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. The frequency of the 106 base pair allele was significantly increased in the groups of English patients with either non-associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's disease or any other autoimmune disorder. For Norwegian patients with either non-associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish patients with either non-associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non-associated Addison's disease or APS2 (P = 0.34 and 0.29, respectively). These results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's disease.

Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant. A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy. In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.